Short- and long-term effects of p-ethynylphenylalanine on brain serotonin levels.
Changes in tissue and extracellular serotonin (5-HT) in raphe dorsalis, raphe medialis and in their main projections areas (hippocampus, striatum and frontal cortex) were investigated at short and long-term times after single injection (5 mg/kg ip) of a novel tryptophan hydroxylase inhibitor, p-ethynylphenylalanine (p-EPA). The 5-HT tissue concentration decreased significantly in raphe nuclei, 30 min post-injection and for 4 days, whereas it decreased from 24 hours post-injection in the 5-HT projections. Normal 5-HT levels reappeared after 12 days post-injection in all areas. Moreover, in the projection areas, the extracellular 5-HT levels decreased rapidly, 90, 40 and 30 min after p-EPA injection, in hippocampus, striatum and frontal cortex, respectively. Decreased accumulation of 5-hydroxytryptophan (5-HTP) under NSD-101 perfusion in the serotoninergic projections after p-EPA injection, confirmed the direct inhibitory effect of the drug on the tryptophan hydroxylase activity. These results demonstrated that p-EPA is a useful pharmacological tool which powerfully, acutely and irreversibly reduces the 5-HT levels.


Epidemiology and changed surgical treatment methods for fractures of the distal radius: a registry analysis of 42,583 patients in Stockholm County, Sweden, 2004–2010.
The incidence of fractures of the distal radius may have changed over the last decade, and operative treatment has been commoner during that time. We investigated the incidence of fractures of the distal radius and changing trends in surgical treatment during the period 2004-2010. Registry data on 42,583 patients with a fracture of the distal radius from 2004 to 2010 were evaluated regarding diagnosis, age, sex, and surgical treatment. The crude incidence rate was 31 per 10(4) person-years with a bimodal distribution. After the age of 45 years, the incidence rate in women increased rapidly and leveled off first at a very high age. The incidence rate in postmenopausal women was lower than previously reported. In men, the incidence was low and it increased slowly until the age of 80 years, when it amounted to 31 per 10(4) person-years. The number of surgical procedures increased by more than 40% despite the fact that there was reduced incidence during the study period. In patients ≥ 18 years of age, the proportion of fractures treated with plating increased from 16% to 70% while the use of external fixation decreased by about the same amount. The incidence rate of distal radius fractures in postmenopausal women appears to have decreased over the last few decades. There has been a shift in surgical treatment from external fixation to open reduction and plating.


Novel intronic RHD variants identified in serologically D-negative blood donors.
Blood group genotyping is used to predict RhD phenotype in transfusion and obstetric medicine. Prediction of antigen D is based on molecular techniques which targets most common RHD-specific polymorphism. However, inactive RHD variants can suggest false-positive RhD phenotype. Their types and frequencies vary among ethnicities. Our study aimed to identify RHD variants among Moroccan blood donors who are serologically D negative. DNA from 53 blood donors who are serologically D negative RhC and/or RhE positive were screened for RHD exon 10 by PCR-SSP. RHD-positive samples were further tested by multiplex PCR covering exons 3, 4, 5, 6, 7 and 9 and then sequenced by targeted next-generation sequencing method. Mutations' impact on mRNA splicing was predicted using alamut software version 2·0. PCR-SSP revealed 9 of 53 (16·9%) RHD-positive samples. Five of nine samples were positive for all tested exons, two of nine were positive for exon 9, and two of nine were undetermined. Sequencing revealed four novel RHD variants based on six mutations in introns 1, 3, 5 and 6. In silico analysis revealed aberrant splicing of three mutations (RHD c.487-1024delG, RHD c.487-256T>G and RHD c.940-187_940-188del), while three other mutations (RHD c.149-682C>A, RHD c.802-37delA and RHD c.939 + 1151dup) had no effect on splicing compared to wild type. All identified RHD variants contain at least one mutation that probably affects splicing to generate D-negative phenotype. Hence, ethnic RhD antigen background must be considered when developing transfusion and obstetric strategies.


Computational Epitope Prediction and Design for Antibody Development and Detection.
The design of optimized protein antigens is a fundamental step in the development of new vaccine candidates and in the detection of therapeutic antibodies. A fundamental prerequisite is the identification of antigenic regions that are most prone to interact with antibodies, namely, B-cell epitopes. Here, we describe an efficient structure-based computational method for epitope prediction, called MLCE. In this approach, all that is required is the 3D structure of the antigen of interest. MLCE can be applied to glycosylated proteins, facilitating the identification of immunoreactive versus immune-shielding carbohydrates.


Synthesis, radiolabeling and in vivo evaluation of [11C]RAL-01, a potential phosphodiesterase 5 radioligand.
Very few tracers are available for imaging studies of second messenger systems. We developed a radiosynthesis for the phosphodiesterase (PDE) 5 inhibitor [(11)C]RAL-01. Whole body distribution studies using positron emission tomography (PET) revealed a time-dependant passage through the liver and accumulation of radioactivity in the bile of the Landrace pig. Displaceable binding was readily discerned in the myocardium, and traces of binding were seen in pulmonary tissue, consistent with the use of this class of drug in the treatment of pulmonary hypertension and heart failure. [(11)C]RAL-01 readily entered the brain and obtained an equilibrium distribution volume of 4-5 ml g(-1). Mean parametric images suggested the presence of a small displaceable binding component, but this binding was not significant in the present group of three pigs. Thus, [(11)C]RAL-01 shows considerable promise for PET studies of biliary elimination and of PDE5 binding in the cardiovascular system. However, analogues of higher affinity may be required for investigations of central nervous system binding sites.


Insecticide toxicity to Trichogramma pretiosum (Hymenoptera: Trichogrammatidae) females and effect on descendant generation.
The effect of nine insecticides used in tomato production was evaluated on adults of two Trichogramma pretiosum Riley (Hymenoptera: Trichogrammatidae) populations from Rive and Afonso Cláudio, Espírito Santo State, Brazil. The experiment was developed in an acclimatized chamber at 25 +/- 1 degrees C, 70 +/- 10% relative humidity and 14 h photophase. Eggs of Anagasta kuehniella (Lepidoptera: Pyralidae), previously immersed in insecticides solutions were offered to females of both T. pretiosum populations. Bacillus thuringiensis, lufenuron and triflumuron had lowest negative effects on parasitism and viability of individuals of these populations; however, abamectin and pyrethroids (betacyflurin 50 and 125 g/l and esfenvalerate) insecticides reduced parasitism rates. T. pretiosum emerged from A. kuehniella eggs treated with esfenvalerate but were not able to parasitize non treated eggs of this host. B. thuringiensis, lufenuron and triflumuron may be used in integrated pest management programs to control tomato pests, because they have moderated negative effect on parasitoid wasps.


[The study of psychological factors and SIgA content in saliva of patients with temporomandibular disorders].
To study the personality, stress, harmful emotions, coping styles and oral immune change of patients with TMD. Using MMPI, LES, Trait coping inventory, SDS, and SAS to test patients and normal control, and using radiate-immune method to determine SIgA content in saliva. The scores of TMD patients in MMPI were significantly higher than those of the normal control (P<0.05, P<0.01), and 10 patients' MMPI results were abnormal. The scores of TMD patients in negative life event and work event were significantly higher than those of the normal control (P<0.05, P<0.01). The scores of TMD patients in PC were significantly lower than those of the normal control, but which in NC were significantly higher than those of the normal control (P<or=0.05, P<0.01). The SAS, SDS scores of TMD patients were significantly higher than those of the normal control (P<0.01). The SIgA contents of TMD patients were significantly lower than those of the normal control (P<0.01),and which were significantly correlated to SDS scores (r=-0.320,P<0.05). TMD patients had abnormal personality, more negative life changes, more negative coping style and harmful emotions, which can induce the high and chronic stress and depression of oral immune function. It may be one of the causes of TMD.


Fatigue failure load of zirconia-reinforced lithium silicate glass ceramic cemented to a dentin analogue: Effect of etching time and hydrofluoric acid concentration.
This study aimed to evaluate the effect of etching time and hydrofluoric acid (HF) concentration on the fatigue failure load and surface characteristics of zirconia-reinforced lithium silicate glass (ZLS) ceramic cemented to a dentin-like, fiber reinforced epoxy resin. Ceramic (Suprinity, VITA) (1.0mm thick) and epoxy resin (2.5mm thick) discs (10mm diameter) were produced. The bonding surface of the ceramic samples was nonetched (control group), or etched for 30, 60 or 90s by 5% or 10% HF. The epoxy resin discs were etched by 10% HF for 30s followed by the application of an adhesive material (Single Bond Universal, 3M ESPE). Pairs of ceramic/epoxy resin discs were cemented with a dual cure resin cement. The fatigue failure load was determined by the staircase method (500,000 cycles at 20Hz; initial load = 925N; step size = 45N). In 10% HF the etching time was shown to influence the fatigue failure load, which increased as the etching time increased (30s < 60s < 90s), and in 5% HF the fatigue failure load was not shown to be affected by the etching time; the lowest fatigue failure loads were produced in the control group without ceramic etching followed by 10% HF acid etching for 30s. Topography analysis showed variations based on the etching protocols. All fractures (radial cracks) were shown to originate from defects at the ceramic surface on the cementing interface. For fatigue loading improvements of ZLS ceramic, 10% HF acid etching for 90s and silanization of the ceramic surface is recommended.


A survey on traditional plants used in Al Khobah village.
The use of traditional medicine for treatment of various diseases is a common practise in most of the developing countries including the Kingdom of Saudi Arabia especially in rural areas. In this survey, Al Khobah village was selected to study the status of Traditional Medicine. Al Khobah village is located on the Southern boarders of the kingdom and characterized by diverse topography and moderate weather. The plants with medicinal uses were collected, identified and their methods of preparation and uses were recorded. After gathering all these information from the local people, literature survey was conducted on each plant to get information about pharmacological activities and weather they support the traditional use or not. The survey revealed that the uses of some plants are consistent with the experimental data in the literature. Some other plants were studied; however, they still need pharmacological investigation to prove the claimed uses. Other plant did not subject to any scientific investigation.


Enhanced production of napthoquinone metabolite (shikonin) from cell suspension culture of Arnebia sp. and its up-scaling through bioreactor.
Cell culture in shake flask and air-lift bioreactor was carried out to exploit the potential of Arnebia sp. for napthoquinone metabolite production. Cell suspension cultures of Arnebia were established from friable callus in liquid MS medium supplemented with 6-benzylaminopurine (BAP) (10 μM) and indole-3-butyric acid (IBA) (5 μM). Growth kinetic studies were done by using settled cell volume and fresh/dry cell weight method. Suspension cultures were maintained by sub-culturing at 10 days interval. A two-stage culture system is employed using growth medium (GM) and modified M9 medium (production medium) for cell biomass and naphthoquinone pigment production, respectively. Results showed that cultivation of cells under dark conditions at room temperature (25 ± 2 °C) enhanced the cell biomass from 100 to 625 g l-1. The pigment production was also found to be increased in dark conditions at room temperature. Alkaline pH found to have positive effect on pigment yield. In case of M9 medium constituents, absence of Na2SO4 does not affect the pigment yield. The current approaches have the cumulative effect to meet an increased level of (25.5 μg/ml) metabolite production in air-lift bioreactor.


Stent graft surface movement after infrarenal abdominal aortic aneurysm repair: comparison of patients with and without a type 2 endoleak.
The aim was to compare multidirectional stent graft movement in patients with and without a type 2 endoleak. This was a retrospective case control study of patients being followed up after elective endovascular aneurysm repair of abdominal aortic aneurysms. The post-procedural and final follow up multislice computed tomography (MSCT) of 69 patients with and 74 without a type 2 endoleak were analyzed. Three dimensional (3D) surface models of the stent graft, delimited by landmarks using custom built software, were derived from these MSCT data. The stent graft was segmented in different zones, and the proportion of the total stent graft surface moving >9 mm between the post-procedural and the final follow up MSCT was calculated, given in percentages, and compared between groups. Changes of infrarenal neck, renal artery to stent graft distance, and freedom from stent graft related endoleaks were evaluated. Overall surface movement was higher in the no endoleak (18.8%, IQR 0.1-45.1%) than in the type 2 endoleak group (5.3%, IQR 0-29.7%; p = .06). Furthermore, significantly higher surface movement in the no endoleak group was found in the proximal anchoring zone (p = .04) and the distal left limb (p = .01), which was the modular limb in 81.1% (p < .01). Neck diameter increase (1.0 mm, IQR 0-3.0 mm; p < .01) and renal artery to stent graft distance difference (0 mm, IQR 0-3.3 mm; p < .01) were significantly higher in the no endoleak group. Five patients in the no endoleak and one patient in the type 2 endoleak group suffered from a stent graft related endoleak (p = .27). The presence of a type 2 endoleak is associated with decreased surface movement of the proximal anchoring zone and the distal modular limb of bifurcated stent grafts.


Perforator flap entity.
The perforator flap is not a new concept in microsurgery but there is still confusion. The number of centers that is using these flaps for various indications is increasing. Studies about the differences between these flaps and the conventional flaps, including donor site morbidity and long-term follow-ups, will be seen in the medical literature. Better accuracy in reconstruction, including the use of only cutaneous tissue, minimization of the morbidity, and preserving the same survival rate in free flaps are reassurances to microsurgeons to perform perforator flaps. We believe that in the near future with refinements in the techniques and instruments, perforator flaps will be the first choice flap.


Environmental tobacco smoke and cancer risk, a prospective cohort study in a Chinese population.
Few prospective cohort studies have investigated associations between environmental tobacco smoke (ETS) and other cancer sites, in addition to lung cancer. We assessed these associations in a population-based prospective cohort study started from 2008 to 2011 with average of 9.1 years of follow-up, in Minhang district, Shanghai, China. The study included a total of 23,415 participants (8388 men, 15,027 women) and 205,515 person-years. Epidemiological data were collected by a standardized questionnaire including ETS exposure. Newly diagnosed patients with primary cancers and deaths were identified by record linkage system with the Shanghai Cancer Registry and Shanghai Vital Statistics. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models, adjusting for potential confounders. During the study period, a total of 1462 patients with diagnoses of primary cancers were identified. Among all participants and non-smokers, ETS was associated with an increased risk of all smoking-related cancers (all: adjusted HR: 1.23, 95% CI: 1.05-1.43 and non-smokers: 1.24, 1.02-1.49), lung cancer (1.29, 0.98-1.71 and 1.27, 0.91-1.77), and stomach cancer (1.86, 1.21-2.85 and 1.75, 1.05-2.91), respectively. Furthermore, associations for lung and stomach cancers were the strongest among non-smoking females. The joint effects of both ETS and active smoking were strongest for all cancers, all smoking-related cancers, lung cancer, and stomach cancer. No clear interactions were observed. These results suggest that ETS exposure may increase the risk of smoking-related cancers in a Chinese population. Further studies on the relationship between ETS exposure and specific cancer sites are warranted to replicate our findings.


Long-term consequences of juvenile vulvar lichen sclerosus: A cohort study of adults with a histologically confirmed diagnosis in childhood or adolescence.
Vulvar lichen sclerosus (VLS) occurs in at least one in 900 girls. There is limited knowledge as to what extent the disease persists in adulthood and what the repercussions in adulthood may be. The aim of this study is to evaluate the long-term consequences of VLS diagnosed in childhood or adolescence. The population of females histologically diagnosed with VLS in childhood or adolescence in the Netherlands between 1991 and 2015 was identified through the national pathology database. Histological specimens were retrieved and re-evaluated. Potential participants for whom the diagnosis was reconfirmed and who are now adults, were then traced and surveyed. Descriptive statistics were calculated and compared with the literature. Main outcome measures are the demographics of the cohort, their scores on standardized quality of life (QoL) and sexuality questionnaires and answers to additional questions regarding patients' experience with the disease. The questionnaires used were the Dermatology Life Quality Index (DLQI), the Skindex-29, the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale-Revised (FSDS-R). Secondary outcome measures include obstetric history and histological features found in the original tissue specimens. A total of 81 women participated, median age 29.0 years, median follow-up from childhood diagnosis 19.5 years. Both QoL and sexuality were somewhat affected in 51.9% of cases. Less than half (45%) reported having regular check-ups. Forty-five (56%) reported symptoms within the past year; of those with symptoms, 14 (31%) were not under surveillance. Cesarean section rate (14.5%) was comparable to the general population, and there were more high-grade obstetric anal sphincter injuries with vaginal deliveries than expected. Sixteen respondents (20%) were not aware of the childhood diagnosis prior to this study. Symptoms due to VLS are reported by most adults diagnosed as juveniles. QoL and sexuality are affected and correlate to recent symptoms. VLS as a juvenile does not preclude a vaginal delivery. Women diagnosed with VLS in childhood or adolescence are often lost to follow-up.


Methadone-induced respiratory depression in the neonatal guinea pig.
Respiratory depression, the most serious side-effect of opioid treatment, is well documented for morphine, the most commonly used opioid in neonatal care. Less is known about methadone, a clinically relevant opioid analgesic, especially during neonatal development. This study was undertaken to determine the neonatal respiratory effects of methadone. We hypothesize that methadone is equipotent to morphine, compared to our previous morphine results in the same animal model, but has a much longer duration of action, due to its longer elimination half-life. Neonatal guinea pigs (3-14 days old) randomly received a single subcutaneous dose of methadone or saline. Using a non-invasive plethysmographic method, we measured ventilatory and metabolic parameters before injection and at intervals for 32 hr after injection while pups breathed "room air" or 5% CO(2) gas mixtures. Methadone-induced depression of ventilation was most evident during 5% CO(2) challenge. The onset of drug effects was within 15 min for all ages and doses, but the duration of action decreased with age. While the depth of methadone-induced respiratory depression did not depend on pup age, the control of breathing was different in 3-day-old pups, where inspiratory time increased fourfold; twice that of older pups. We conclude that methadone induces a naloxone reversible respiratory depression in guinea pig neonates and, in the very young, causes an abnormal breathing pattern due to changes in respiratory timing. Methadone is more potent than morphine with respect to neonatal respiratory depression, but surprisingly, the duration of methadone action was not longer than morphine.


Clinical outcomes and prognostic factors of Ewing sarcoma: a clinical analysis of 12 patients in Taiwan.
Ewing sarcoma is extremely rare in people from East and Southeast Asia. The records of 12 patients diagnosed with primary Ewing sarcoma and treated at our institution from 1997 to 2009 were retrospectively reviewed. There were seven male and five female patients and their mean age at diagnosis was 22 years (range, 12-48 years). Two patients (16.7%) had distant metastasis at diagnosis. The primary tumor sites were the trunk in seven patients (58.3%) and the extremities in five patients (41.7%). Eleven patients received neoadjuvant chemotherapy followed by wide excision surgery, and then adjuvant chemotherapy. One patient received only chemotherapy without surgical intervention due to poor cardiac and pulmonary function. At a mean follow-up of 33 months, the 2-year overall survival rate (OS) was 45.5%. Distant metastasis was the only statistically significant prognostic factor of OS in our study. The 2-year OS rates of patients with lung metastasis and without lung metastasis were 0% and 42.9%, respectively (p = 0.021). The t(11;22)(q24:q12) translocation was present in all patients in our series. We confirmed that distant metastases is highly predictive of a poor outcome, and that the t(11;22)(q24:q12) translocation was present in all patients in our series.


Clinicopathological and molecular characteristics of fumarate hydratase-deficient uterine smooth muscle tumors: a single-center study of 52 cases.
The fumarate hydratase (FH) gene germline mutations cause hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC), predisposing carriers to uterine and cutaneous leiomyomas and renal cell carcinoma. In this study, we aim to investigate morphology and the correlation between FH mutation in FH-deficient (FH-d) uterine smooth muscle tumors (uSMTs). We conducted immunohistochemical staining in 161 cases of uSMTs to detect FH deficiency. We identified 52 cases (52/161, 32%) of FH-d, including 34 leiomyomas with bizarre nuclei, 10 uSMTs of uncertain malignant potential (STUMPs), 4 cellular leiomyomas, 3 usual type leiomyomas, and 1 leiomyosarcoma. Patients with FH-d were aged 24-67 years (median, 40 years). The most common FH-d morphological features included staghorn-shaped blood vessels (87%), bizarre nuclei (81%), alveolar pattern edema (65%), macronucleoli surrounded by a halo (65%), cytoplasmic eosinophilic globules (56%), and chain-like distribution of smooth muscle cells (52%). A targeted next-generation sequence was performed in 11 of 52 FH-d tumors. Five cases (5/11, 45%) were found with FH germline mutations, including 4 leiomyomas with bizarre nuclei and 1 STUMP. The median age of patients with germline FH mutation was 30 years. The germline mutations included 3 pathogenic, 1 likely pathogenic, and 1 rare uncertain clinical significance variants. Our results revealed that FH-d uSMTs usually exhibit the distinct morphology features and high frequency of FH germline mutations. The combination of predictive morphology evaluation, FH immunotype, and molecular testing is helpful for the screening of HLRCC in uSMTs.


Cell-mediated immunity and its glucocorticoid-sensitivity after clinical recovery from severe major depressive disorder.
This follow-up study investigated lymphocyte blastogenesis induced by concanavalin A, phytohemagglutinin A, and pokeweed mitogen and their sensitivity to in vitro dexamethasone administration in 12 patients clinically recovered from severe major depression. Although cortisol-levels at 4.00 p.m. decreased significantly after clinical remission, mitogen-driven lymphocyte proliferative responses were unchanged when assessed intra-individually. No impairment of in vitro glucocorticoid-sensitivity of lectin-induced lymphocyte blastogenesis could be observed in clinically recovered patients. The inhibitory potency of in vitro dexamethasone was found to be inversely correlated with in vivo adrenal cortical hormone levels. There were no correlations with age, weight, sex, antidepressant medication, severity or duration of depression. No differences from age- and sex-matched healthy individuals were found. These results indicate that reduced glucocorticoid receptor sensitivity occurs only during the acute depressive illness.


Structural basis for dimerization quality control.
Most quality control pathways target misfolded proteins to prevent toxic aggregation and neurodegeneration1. Dimerization quality control further improves proteostasis by eliminating complexes of aberrant composition2, but how it detects incorrect subunits remains unknown. Here we provide structural insight into target selection by SCF-FBXL17, a dimerization-quality-control E3 ligase that ubiquitylates and helps to degrade inactive heterodimers of BTB proteins while sparing functional homodimers. We find that SCF-FBXL17 disrupts aberrant BTB dimers that fail to stabilize an intermolecular β-sheet around a highly divergent β-strand of the BTB domain. Complex dissociation allows SCF-FBXL17 to wrap around a single BTB domain, resulting in robust ubiquitylation. SCF-FBXL17 therefore probes both shape and complementarity of BTB domains, a mechanism that is well suited to establish quality control of complex composition for recurrent interaction modules.


The metastatic T-cell hybridoma antigen/P-selectin glycoprotein ligand 1 is required for hematogenous metastasis of lymphomas.
Using variants of the murine BW5147 lymphoma cell-line, we have previously identified 3 monoclonal antibodies (MAbs) that discriminate between metastatic and nonmetastatic BW5147-derived T-cell hybridomas and lymphomas, as well as BW5147-unrelated T-lymphomas. These MAbs were reported to recognize an identical membrane-associated sialoglycoprotein, termed "metastatic T-cell hybridoma antigen" (MTH-Ag). Here, we document that the expression pattern of the MTH-Ag on metastatic and nonmetastatic BW5147 variants correlates with that of the P-selectin glycoprotein ligand 1 (PSGL-1), a sialomucin involved in leukocyte recruitment to sites of inflammation. Moreover, the MAbs against the MTH-Ag recognize PSGL-1 when it is transfected in MTH-Ag-negative BW5147 variants, suggesting that the MTH-Ag is PSGL-1. Overexpression of MTH-Ag/PSGL-1 in MTH-Ag-negative BW5147 variants did not affect their in vivo malignancy. Yet, down-regulation of MTH-Ag/PSGL-1 expression on metastatic, MTH-Ag-positive BW5147 variants, using an RNA interference (RNAi) approach, resulted, in a dose-dependent manner, in a significant reduction of liver and spleen colonization and a delay in mortality of the recipient mice upon intravenous inoculation. Collectively, these results demonstrate that, although MTH-Ag/PSGL-1 overexpression alone may not be sufficient for successful dissemination and organ colonization, MTH-Ag/PSGL-1 plays a critical role in hematogenous metastasis of lymphoid cancer cells.


The effect of deferoxamine on tolerance to secondary ischaemia caused by venous obstruction.
The current study investigated the efficacy of deferoxamine for treating secondary ischaemia due to venous obstruction in a rodent epigastric pedicle flap model. Rats receiving one dose of the free radical scavenger and iron chelator deferoxamine (150 mg/kg) intravenously prior to reperfusion had a mild improvement in flap survival: 46% in controls, 77% in deferoxamine-treated. This was statistically significant at p less than 0.05 (chi 2 = 5.2). This suggests that free radicals are partly involved in the mechanism of ischaemia/reperfusion injury in secondary ischaemia, as has been previously demonstrated for primary ischaemia (Angel et al., 1986b). Supporting biochemical evidence will be necessary to understand better the mechanisms involved in secondary ischaemia.


["Teddy bear granuloma", a rare condition: a case report of a 3-year-old child].
Conjunctival synthetic fiber granulomas, or "Teddy bear granulomas", are rare granulomatous responses to synthetic fabric fibers. We report the case of a 3-year-old boy with no prior infectious or traumatic history, brought in by his parents for an incidentally discovered conjunctival growth in his right eye. Slit lamp examination revealed a 10-mm growth in the inferior fornix surrounding a small greyish foreign body. Surgical excision and histopathology revealed granulomatous inflammatory cell response with foreign body giant cells surrounding exogenous material. This foreign material was birefringent in polarized light, very suggestive of synthetic fabric fibers, which permitted the diagnosis of Teddy bear granuloma. Synthetic fiber granulomas present in children as unilateral, more or less inflammatory growths in the inferior conjunctival fornix. Surgical excision with histopathology makes the diagnosis and effects the cure.


Formation of haloacetonitriles and haloacetamides and their precursors during chlorination of secondary effluents.
The formation of dichloroacetonitrile (DCAN), dichloroacetamide (DCAcAm) and trichloroacetamide (TCAcAm) during chlorination of secondary effluents was evaluated under different conditions. The formation of DCAN and DCAcAm increased, then decreased with increasing contact time and chlorine dose, while TCAcAm formation increased continually, exceeding DCAcAm formation after a relatively long contact time or in response to a relatively high chlorine dose (20-80 mg L(-1)). Increasing the sample pH from 6 to 9 reduced the formation of DCAN and TCAcAm, while DCAcAm formation was highest at pH 8. Precursors in the secondary effluent were characterized by separating the organic matter into several fractions using membrane filtration and XAD resins and then measuring the formation of DCAN, DCAcAm and TCAcAm from each fraction during chlorination. Dissolved organic matter (DOM) with a molecular weight less than 1 kDa dominated the formation of DCAcAm and TCAcAm. However, particle-associated DCAN precursors were detected in addition to potent DCAN precursors in the DOM fractions. Among the XAD fractions of DOM, the hydrophilic neutral fraction prevailed in the secondary effluent and produced the most DCAN, DCAcAm and TCAcAm per volume, and the hydrophilic basic fraction with a low organic content had the highest yields of DCAN, DCAcAm and TCAcAm on a DOC basis, so their dominant precursors were associated with hydrophilic matter.


Arthroscopic versus open distal clavicle excision: a comparative assessment at intermediate-term follow-up.
While few comparative studies exist, it has been suggested that open distal clavicle excisions (DCEs) provide inferior results when compared with the all-arthroscopic technique. The purpose of this study was to compare the intermediate-term (5-year follow-up) results of patients undergoing arthroscopic versus open DCE for the treatment of recalcitrant acromioclavicular joint pain. Cohort study; Level of evidence, 3. All patients who underwent an arthroscopic or open DCE between January 1999 and September 2006 were reviewed. Forty-eight patients (49 shoulders; 32 arthroscopic, 17 open) following DCE without significant glenohumeral pathologic changes were included. The mean follow-up for group I (open) and group II (arthroscopic) was 5.3 years and 4.2 years, respectively. The American Shoulder and Elbow Surgeons (ASES) score, visual analog scale (VAS) pain score, surgical time, and minimum radiographic acromioclavicular joint distance were calculated. Each patient completed a questionnaire assessing their scar satisfaction, percentage of normal shoulder function, and willingness to have the surgery again. Risk factors for poor outcomes were analyzed. Arthroscopic patients had significantly less pain (P = .035) by VAS (0.61 ± 1.02) compared with open (1.59 ± 2.15) at final follow-up. There was no significant difference between group I and group II with regard to ASES (87.5 ± 17.6 vs 94.6 ± 8.6), percentage of normal shoulder function (89.7% ± 12.5 vs 92.9% ± 8.6), average operative time (53.1 minutes vs 48 minutes), or radiographic resection distance (12.8 ± 2.1 mm vs 9.5 ± 2.9 mm). In the open group, patients with 16 of 17 shoulders were satisfied with their scar and 100% would do it again. In the arthroscopic group, patients with 31 of 32 shoulders (97%) were both satisfied and would have the surgery again. Open and arthroscopic DCE are both effective surgeries to treat recalcitrant acromioclavicular joint pain. At intermediate-term follow-up, they provide similarly good to excellent results with regard to patient satisfaction and shoulder function. Although both are effective treatments, less residual pain was found using the arthroscopic technique.


Logic gate-driven dual-index balanced visualization strategy for tumor metastasis diagnosis.
Exfoliated tumor cells are integral to malignant tumors diagnosis. The process of clinical cytology of exfoliation involves several complex steps that require at least two days of preparation. Here, we develop a balanced-etching visual kit based on concentration differences of Glutathione/Glucose (GSH/Glu) to distinguish normal from exfoliated tumor cells rapidly and accurately. The balanced-etching visualization kit can be used to obtain color cards and screen exfoliated tumor cells initially (within 10 min). Furthermore, by utilizing logic gates and machine learning algorithms for RGB extraction of the color card obtained from the kit, accurate screening of exfoliated tumor cells is achieved. Finally, a series of clinical tumor samples, such as urine, pleural fluids, ascites, and gastric fluids, have been validated. With effective experimental methods, accurate disease information, and appropriate therapeutic programs, the novel diagnostic strategy is expected to promote precision medicine.


A novel protocol to induce mental fatigue.
Mental fatigue is a commonplace human experience which is the focus of a growing body of research. Whilst researchers in numerous disciplines have attempted to uncover the origins, nature, and effects of mental fatigue, the literature is marked by many contradictory findings. We identified two major methodological problems for mental fatigue research. First, researchers rarely use objective measures of mental fatigue. Instead, they rely heavily on subjective reports as evidence that mental fatigue has been induced in participants. We aimed to develop a task which led to not only a subjective increase in mental fatigue, but a corresponding performance decrement in the mentally fatiguing task as an objective measure. Secondly, current mental fatigue paradigms have low ecological validity - in most prior studies participants have been fatigued with a single repetitive task such as the n-back or Stroop. To move towards a more ecologically valid paradigm, our participants undertook a battery of diverse cognitive tasks designed to challenge different aspects of executive function. The AX-CPT, n-back, mental rotation, and visual search tasks were chosen to challenge response inhibition, working memory, spatial reasoning, and attention. We report results from 45 participants aged 19 to 63 years who completed a two-hour battery comprising four different cognitive tasks. Subjective fatigue ratings and task performance were measured at the beginning and end of the battery. Our novel method resulted in an increase in subjective ratings of fatigue (p < 0.001) and a reduction in task performance (p = 0.008). Future research into mental fatigue may benefit from using this task battery.


Evaluation of cast wedging in a forearm fracture model.
In paediatric traumatology fractures are commonly treated with a cast. In this course cast wedging is sometimes performed aiming to reduce the fracture angulation. However, the impact of various factors and measures such as cast material, optimal position of the wedge and wrist position were not assessed in a systematic manner. A laser supported model was developed to evaluate the biomechanical processes of cast wedging manoeuvre in a model of a distal diaphyseal forearm fracture. Consecutive measurements were performed to find out the influence of wedge position, cast material and wrist position. The result of the manoeuvre was revealed to be independent of the cast material (plaster of Paris vs. synthetic cast) used. The optimal position for placing the wedge was shown to be on the concave side of the cast at the level of the fracture. The result of a cast wedging manoeuvre in a dorsally displaced forearm fracture can be optimized with the wrist held in extension. The cast wedging model is not a meticulous copy of the human anatomy but it allows some basic studies on cast wedging technique. The results that can be achieved are similar to the experiences of practical paediatric traumatology. Furthermore the present model may be beneficial for use in education and training programs.


Excitation of autonomic nerves by 4-aminopyridine in the isolated, blood-perfused sino-atrial node preparation of the dog.
4-Aminopyridine injected into the sinus node artery produced a long-lasting decrease in sinus rate preceded by a transient increase. With a large dose, a long-lasting increase in sinus rate was superimposed on the long-lasting decrease phase. The long-lasting decrease and increase in sinus rate were abolished by 1-hyoscyamine and propranolol respectively, and both were reduced by tetrodotoxin. These results can be interpreted as being due to excitation of autonomic nerves by 4-aminopyridine.


Synthesis and characterization of a novel mucoadhesive derivative of xyloglucan.
A novel polymer in the form of a thiolated derivative of natural tamarind seed polysaccharide or xyloglucan was synthesized and its chacteristics as a mucoadhesive polymer were studied as a part of the study undertaken herein. The synthetic route followed involves a two-step reaction mechanism of firstly oxidizing xyloglucan and then further conjugating it with l-cysteine to form thiolated xyloglucan or thiomer via imine linkage. The thiomer thus formed was characterized using various analytical techniques as differential scanning calorimetry (DSC), X-ray diffraction analysis (XRD), and nuclear magnetic resonance (NMR). Ellman's method was used to determine the numbers of thiol groups/g of thiolated xyloglucan. Zeta potential measurements were carried out for thiolated xyloglucan. Viscosities of the formulated xyloglucan and thiolated xyloglucan gels were comparatively evaluated along with the evaluation of mucoadhesive properties of the gels using ex vivo bioadhesion study employing freshly excised sheep intestinal mucosa.


SIC, an intracerebral beta(+)-range-sensitive probe for radiopharmacology investigations in small laboratory animals: binding studies with (11)C-raclopride.
Our aim was to show the ability of a recently developed beta(+)-range-sensitive intracerebral probe (SIC) to measure, in vivo, the binding of radioligands in small animals. The potential of the device for pharmacokinetic studies was evaluated by measurement of the dynamic striatal binding of (11)C-raclopride, a well-documented D(2) dopaminergic receptor ligand, in rat brain after intravenous injection of the labeled compound. The effects of preinjection of the unlabeled ligand (raclopride, 2 mg/kg intravenously) and of increasing the synaptic dopamine level (amphetamine treatment, 1 mg/kg intravenously) or of depleting synaptic dopamine (reserpine pretreatment, 5 mg/kg intraperitoneally) on in vivo (11)C-raclopride binding were monitored by SIC. The radioactivity curves measured as a function of time were reproducible and consistent with previous studies using PET imaging (ratio of striatum to cerebellum, 2.6 +/- 0.3 after 20 min). Further studies showed significant displacement of (11)C-raclopride by its stable analog. Finally, the device proved its capacity to accurately detect changes in (11)C-raclopride binding after a sudden (amphetamine) or a gradual (reserpine) modulation of endogenous dopamine levels. These results show that the new device can monitor binding of PET ligands in anesthetized rodents in vivo, with high temporal resolution.


Lung mesenchymal stromal cells influenced by Th2 cytokines mobilize neutrophils and facilitate metastasis by producing complement C3.
Pre-metastatic niche formation is critical for the colonization of disseminated cancer cells in distant organs. Here we find that lung mesenchymal stromal cells (LMSCs) at pre-metastatic stage possess potent metastasis-promoting activity. RNA-seq reveals an upregulation of complement 3 (C3) in those LMSCs. C3 is found to promote neutrophil recruitment and the formation of neutrophil extracellular traps (NETs), which facilitate cancer cell metastasis to the lungs. C3 expression in LMSCs is induced and sustained by Th2 cytokines in a STAT6-dependent manner. LMSCs-driven lung metastasis is abolished in Th1-skewing Stat6-deficient mice. Blockade of IL-4 by antibody also attenuates LMSCs-driven cancer metastasis to the lungs. Consistently, metastasis is greatly enhanced in Th2-skewing T-bet-deficient mice or in nude mice adoptively transferred with T-bet-deficient T cells. Increased C3 levels are also detected in breast cancer patients. Our results suggest that targeting the Th2-STAT6-C3-NETs cascade may reduce breast cancer metastasis to the lungs.


Aliskiren: the first renin inhibitor for clinical treatment.
The first evidence of the existence of renin was presented over 100 years ago. However, the importance of renin and the renin-angiotensin system in the pathogenesis of cardiovascular disease was only fully realized in the 1970s. It was another 20 years before the first inhibitors of renin were available for clinical research. Here, we describe the discovery and development of aliskiren, an orally active renin inhibitor, which became the first drug in its class to receive regulatory approval. In 2007, it was approved for the treatment of hypertension by the US Food and Drug Administration and the European Medicines Agency.


The Canadian Food Intake Screener for assessing alignment of adults' dietary intake with the 2019 Canada's Food Guide healthy food choices recommendations: scoring system and construct validity.
The Canadian Food Intake Screener was developed to rapidly assess alignment of dietary intake with the Canada's Food Guide-2019 healthy food choices recommendations. Scoring is aligned with the Healthy Eating Food Index-2019 to the extent possible. Among a sample of adults, reasonable variation in screener scores was noted, mean screener scores differed between some subgroups with known differences in diet quality, and a moderate correlation between screener scores and total Healthy Eating Food Index-2019 scores based on repeat 24 h dietary recalls was observed. The Canadian Food Intake Screener has moderate construct validity for rapid assessment of overall alignment of adults' dietary intake with the Canada's Food Guide-2019 healthy food choices recommendations.


The effect of metronidazole on TPN-associated liver dysfunction in neonates.
The effect of metronidazole (MNZ) on hepatic dysfunction associated with total parenteral nutrition (TPN) in neonates was investigated. Neonates receiving TPN for more than 2 weeks were divided into three groups. In group 1, TPN was given alone, in group 2, 25 mg/kg/d of MNZ was administered intravenously for the first 2 weeks of TPN, and in group 3, 50 mg/kg/d of MNZ was given for the first 3 weeks of TPN. Several parameters of liver function tests (LFTs) during the first 4 weeks of TPN were compared among these three groups. There was no significant difference of these parameters between group 1 and group 2. Although there was no significant difference of alkaline phosphatase, gamma-glutamyl transpeptidase, direct bilirubin, and total bile acid between groups 1 and 3, transaminase (glutamic oxaloacetic, glutamic pyruvic) of group 3 remained significantly lower than those of group 1. In conclusion, the administration of MNZ 50 mg/kg/d for 3 weeks, at least, prevented the elevation of transaminase during TPN in neonates, suggesting the possible involvement of intestinal anaerobic flora in the pathogenesis of TPN-associated liver dysfunction.


Impacts of fast production of afucosylated antibodies and Fc mutants in ExpiCHO-S™ for enhancing FcγRIIIa binding and NK cell activation.
This study has employed mammalian transient expression systems to generate afucosylated antibodies and antibody Fc mutants for rapid candidate screening in discovery and early development. While chemical treatment with the fucose analogue 2-fluoro-peracetyl-fucose during transient expression only partially produced antibodies with afucosylated N-glycans, the genetic inactivation of the FUT8 gene in ExpiCHO-S™ by CRISPR/Cas9 enabled the transient production of fully afucosylated antibodies. Human IgG1 and murine IgG2a generated by the ExpiCHOfut8KO cell line possessed a 8-to-11-fold enhanced FcγRIIIa binding activity in comparison with those produced by ExpiCHO-S™. The Fc mutant S239D/S298A/I332E produced by ExpiCHO-S™ had an approximate 2-fold higher FcγRIIIa affinity than that of the afucosylated wildtype molecule, although it displayed significantly lower thermal-stability. When the Fc mutant was produced in the ExpiCHOfut8KO cell line, the resulting afucosylated Fc mutant antibody had an additional approximate 6-fold increase in FcγRIIIa binding affinity. This synergistic effect between afucosylation and the Fc mutations was further verified by a natural killer (NK) cell activation assay. Together, these results have not only established an efficient large-scale transient CHO system for rapid production of afucosylated antibodies, but also confirmed a cooperative impact between afucosylation and Fc mutations on FcγRIIIa binding and NK cell activation.


Postpartum depression and associated factors among mothers who gave birth in the last twelve months in Ankesha district, Awi zone, North West Ethiopia.
Postpartum depression is the most common complication of childbearing age women and is a considerable public health problem. The transition into motherhood is a difficult period that involves significant changes in the psychological, social and physiological aspects, and has increased vulnerability for the development of mental illness. More than 1 in 10 pregnant women and 1 in 20 postnatal women in Ethiopia suffer from undetected depression. Community based cross sectional study was conducted among 596 postpartum mothers in Ankesha District, North West Ethiopia, from February 01 to March 2, 2018. One stage cluster sampling technique was employed to get the study participants. The objective was to assess the prevalence and associated factors of postpartum depression among mothers who gave birth in the last Twelve months in Ankesha District, Awi Zone, North West Ethiopia, 2018. The interviewer-administered questionnaire was used to collect data and Eden Burg Postpartum Depression Scale was used to assess postpartum depression with cutoff point ≥8. The data were entered into Epi data version 3.1 and exported to SPSS version 24 for analysis. All variables with P < 0.25 in the bivariate analysis were included in the final model and statistical significance was declared at P < 0.05. In this study, a total of 596 study participants were involved making a response rate of 97.4%, the prevalence of postpartum depression was 23.7% with 95%CI: 20.3-27.2. From the participant mothers who are divorced/widowed/unmarried (AOR = 3.45 95%CI: 1.35-8.82), unwanted pregnancy (AOR = 1.95 95%CI: 1.14-3.33), unpreferred infant sex (AOR = 1.79 95%CI: 1.13-2.86), infant illness (AOR = 2.08 95%CI: 1.30-3.34) and low social support (AOR = 3.16 95% CI: 1.55-6.43) was independent predictors of postpartum depression. Almost a quarter (23.7%) of women suffers from postpartum depression. Marital status, unwanted pregnancy, unwanted infant sex, infant illness, and low social support were independent predictors of postpartum depression. Therefore, integration of mental illness with maternal and child health care is important, information communication education and behavioral change communications on postpartum depression are better been given attention.


Infection control response to an outbreak of OXA-23 carbapenemase-producing carbapenem-resistant Acinetobacter baumannii in a skilled nursing facility in Utah.
Antibiotic-resistant Acinetobacter species are a growing public health threat, yet are not nationally notifiable, and most states do not mandate reporting. Additionally, there are no standardized methods to detect Acinetobacter species colonization. An outbreak of carbapenem-resistant Acinetobacter baumannii (CRAB) was identified at a Utah ventilator unit in a skilled nursing facility. An investigation was conducted to identify transmission modes in order to control spread of CRAB. Culture-based methods were used to identify patient colonization and environmental contamination in the facility. Of the 47 patients screened, OXA-23-producing CRAB were detected in 10 patients (21%), with 7 patients (15%) having been transferred from out-of-state facilities. Of patients who screened positive, 60% did not exhibit any signs or symptoms of active infection by chart review. A total of 38 environmental samples were collected and CRAB was recovered from 37% of those samples. Whole genome sequencing analyses of patient and environmental isolates suggested repeated CRAB introduction into the facility and highlighted the role of shared equipment in transmission. The investigation demonstrated this ventilated skilled nursing facility was an important reservoir for CRAB in the community and highlights the need for improved surveillance, strengthened infection control and inter-facility communication within and across states.


New Insights in Preterm Nutrition.
Nutrition of preterm infants has a crucial role in the promotion of organ's optimal growth and development [...].


Colonoscopic manifestations of typhoid fever with lower gastrointestinal bleeding.
Intestinal bleeding in patients with typhoid fever usually occurs in the ileum. However, endoscopic findings in such patients are not well established. We examined the colonoscopic manifestations of intestinal lesions with bleeding in patients with typhoid fever. The colonoscopic findings of seven patients who presented with haematochezia due to typhoid fever were reviewed retrospectively. Typhoid fever was diagnosed when the Salmonella typhi was isolated or when the Widal test showed strongly positive reactions. Clinical data and colonoscopic findings were reviewed in seven patients (four men and three women with an average age of 42 years). The most commonly involved area was the terminal ileum (100%), followed by the ileocecal valve (57%), the ascending colon (43%), and the transverse colon (29%). Left colon was intact in all cases. The most common colonoscopic finding was multiple variable-sized punched-out ulcers with slightly elevated margin, as found in five patients. In two patients, only several oedematous hyperaemic mucosal patches with haemorrhagic spots or shallow erosions were seen. Active bleeding was noticed only in one patient, who received endoscopic haemostasis twice. The remaining six patients were treated by conservative treatment including antibiotic therapy. There was no complication during or after the colonoscopic examination. Intestinal bleeding in typhoid fever usually occurs from the ulcers in the ileum or proximal colon, and the most common colonoscopic manifestations are multiple variable-sized punched-out ulcerations.


Clearing the final HIPAA hurdle: preparing for compliance with the HIPAA Security Rule.
On Feb. 20, while most health care providers were in the midst of last-minute preparations to comply with the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule, the Department of Health and Human Services (DHHS) published the final HIPAA Security Rule.


Enhanced Homing of CXCR-4 Modified Bone Marrow-Derived Mesenchymal Stem Cells to Acute Kidney Injury Tissues by Micro-Bubble-Mediated Ultrasound Exposure.
Although the curative effects of bone marrow stromal cells (BMSCs) for acute kidney injury (AKI) have been recognized, their in vivo reparative capability is limited by the low levels of targeted homing and retention of intravenous injected cells. Stromal cell-derived factor-1 (SDF-1) plays an important role in stem cell homing and retention through interaction with its specific functional receptor, CXCR4, which is presumably related to the poor homing in AKI therapy. However, most of the functional CXCR4 chemokine receptors are lost upon in vitro culturing. Ultrasound-targeted micro-bubble destruction (UTMD) has become one of the most promising strategies for the targeted delivery of drugs and genes. To improve BMSC homing to AKI kidneys, we isolated and cultured rat BMSCs to third passage and enhanced CXCR-4 transfection efficiency in vitro by applying UTMD and polyethylenimine. Transwell migration assay showed that the migration ability of CXCR4-modified BMSCs was nine-fold higher than controls. Then, mercuric chloride-induced AKI rats were injected with transfected BMSCs through their tail veins. We showed that enhanced homing and retention of BMSCs were observed in the CXCR-4 modified group compared with other groups at 1, 2 and 3 d post-treatment. Collectively, our data indicated that UTMD was an effective method to increase BMSCs' engraftment to AKI kidney tissues by increasing CXCR-4 expression.


A randomized, double-blind, placebo-controlled trial of prophylactic recombinant human granulocyte-macrophage colony-stimulating factor to reduce nosocomial infections in very low birth weight neonates.
We carried out a randomized placebo-controlled trial in very low birth weight neonates (VLBWNs), comparing the incidence of nosocomial infections after the prophylactic use of recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) versus placebo in VLBWNs. VLBWNs (n = 264), weighing 501 to 1000 g, </=72 hours of age were randomly assigned to receive rhu GM-CSF (8 microg/kg/d), administered intravenously (n = 134) over 2 hours daily x 7 days and every other day for 21 days, or placebo (n = 130). The safety, incidence of nosocomial infections, days of absolute neutrophil count >/=4000/mm,3 peripheral blood progenitor studies, and 24-hour polymorphonuclear leukocyte C3bi receptor expression were compared between the 2 treatment groups. No (grade III/IV) toxicity or adverse events were associated with rhu GM-CSF. The absolute neutrophil count and absolute eosinophil count were significantly elevated in the rhu GM-CSF group on days 7 (P =.001), 14 (P =.001), and 21 (P =.007) and on days 7 and 28 (P =.012 and P =.001, respectively). However, there was no difference in the incidence of confirmed nosocomial infections between the 2 treatment groups in this trial (40% vs 39%, rhu GM-CSF vs placebo; P = NS). In a large randomized placebo-controlled trial, prophylactic administration of rhu GM-CSF in VLBWNs does not appear to decrease the incidence of nosocomial infections.


Optic Radiation Tractography and Visual Field Deficits in Laser Interstitial Thermal Therapy for Amygdalohippocampectomy in Patients with Mesial Temporal Lobe Epilepsy.
Laser interstitial thermal therapy (LITT) has become an alternative to open-resective surgery for refractory mesial temporal lobe epilepsy (MTLE). Occurrence of visual field defects (VFDs) following open surgery for MTLE is reported at 52-100%. We examined the rate of VFDs following LITT for amygdalohippocampectomy (AHE) and correlated the occurrence of VFDs with damage to the optic radiations, assessed by diffusion tensor tractography (DTI). We performed a retrospective analysis of 5 patients who underwent LITT-AHE for medically refractory MTLE. We examined the association between VFDs and optic radiation damage by correlating postprocedural visual field testing with qualitative assessment of optic radiation fiber tracts. Postoperative assessments showed that 4 patients had normal visual field testing, and 1 had a right superior quadrantanopsia (20%). We performed 3-dimensional reconstruction of the optic radiation, laser probe trajectory, and ablation volume. Damage to Meyer's loop was determined consistent with the VFD. Short-term follow-up in our series suggests that laser ablation AHE may be associated with a lower rate of VFD than has been reported for open AHE. Our results suggest that incorporating optic radiation mapping through DTI may preoperatively help to minimize the risk of VFD following laser ablation AHE.


High molecular weight adiponectin activates AMPK and suppresses cytokine-induced NF-kappaB activation in vascular endothelial cells.
Various isoforms of adiponectin circulate in the plasma. We purified high molecular weight (HMW) adiponectin from human plasma. HMW adiponectin was observed to activate AMP-activated protein kinase (AMPK), thereby increasing the phosphorylation of eNOS and NO production in endothelial cells. On the other hand, cells preincubated with HMW adiponectin had reduced TNFalpha-induced NF-kappaB activation. HMW adiponectin by itself was found to modestly activate NF-kappaB, which was significantly enhanced by inhibition of AMPK/eNOS activation. Thus, HMW adiponectin might have dual action, both pro and anti-inflammatory. An initial period of NF-kappaB activation by HMW adiponectin might be proinflammatory, but it could be counteracted by activation of AMPK/eNOS, which lead to a potential reduction in a second activation of NF-kappaB against inflammatory stimuli.


Stereospecificity in toxicity of the optical isomers of EPN.
While the optical isomers of EPN were equally toxic to mice, (+)-EPN was 2.9 fold and 4.0 fold more toxic to houseflies and rice stem borer larvae, respectively, than the (-)-isomer. In addition, (-)-EPN produced paralysis of the legs in hens about 10 to 14 days after dosing, whereas (+)-EPN caused no paralytic effects. Thus, (+)-EPN appears to be a more appropriate insecticide than the racemic compound, since it combines high toxicity to insects and no delayed neruotoxicity in hens.


Subverting sterols: rerouting an oxysterol-signaling pathway to promote tumor growth.
Oxysterols are oxidized derivatives of cholesterol that are generated enzymatically or through autoxidation. Initially identified as important lipid signaling molecules in the context of atherosclerosis and inflammation, accumulated evidence indicates that these lipid-signaling molecules can have pleiotropic effects on the fate and function of the immune system. These effects range from the regulation of immune cell survival and proliferation to chemotaxis and antiviral immunity. New studies now indicate that tumor-derived oxysterols can serve to subvert the immune system by recruiting protumorigenic neutrophils into the tumor microenvironment. The consequence of this recruitment is the generation of proangiogenic factors and matrix metalloproteinase proteins that provide a tumor a significant growth and survival advantage. In combination with other recent studies, these data highlight the ongoing cross talk between sterol metabolism and the immune system, and they raise the intriguing possibility that targeting oxysterol pathways could serve as a novel therapeutic approach in the war on cancer.


Fetal heart rate monitoring in labor: from pattern recognition to fetal physiology.
The journey of human labor involves hypoxic and mechanical stresses as a result of progressively increasing frequency, duration and strength of uterine contractions and resultant compression of the umbilical cord. In addition, occlusion of the spiral arteries during myometrial contractions also leads to repetitive interruptions in the utero-placental circulation, predisposing a fetus to progressively worsening hypoxic stress as labor progresses. The vast majority of fetuses are equipped with compensatory mechanisms to withstand these hypoxic and mechanical stresses. They emerge unharmed at birth. However, some fetuses may sustain an antenatal injury or experience a chronic utero-placental insufficiency prior to the onset of labor. These may impair the fetus to compensate for the ongoing hypoxic stress secondary to ongoing uterine contractions. Non-hypoxic pathways of neurological damage such as chorioamnionitis, fetal anemia or an acute fetal hypovolemia may potentiate fetal neurological injury, especially in the presence of a super-imposed, additional hypoxic stress. The use of utero-tonic agents to induce or augment labor may increase the risk of hypoxic-ischemic injury. Clinicians need to move away from "pattern recognition" guidelines ("normal," "suspicious," "pathological"), and apply the knowledge of fetal physiology to differentiate fetal compensation from decompensation. Individualization of care is essential to optimize outcomes.


Relationship of serum ACE inhibition to oral dose of enalapril in normotensive volunteers.
To determine the relationship between oral dose of enalapril and parameters describing serum angiotensin converting enzyme (ACE) inhibition. Four different oral doses of enalapril maleate (2.5, 5, 10 and 20 mg) were administered to six healthy normotensive volunteers, in a four-period crossover study. Serum ACE inhibition profiles were determined in each case using a synthetic substrate, hippuryl-histidyl-leucine (HHL). Pharmacodynamic parameters of the drug (Emax and AUEC0-->24) were calculated and their relationship to oral doses investigated using linear regression analysis. There was no significant relationship between drug dose and the two pharmacodynamic parameters (Emax and AUEC0-->24). The r2 values were 0.548 (F=3.63, P=0.153) and 0.6360 (F=5.24, P=0.106) for Emax and AUEC0-->24, respectively. The extent of serum ACE inhibition, as the main determinant of the blood pressure lowering effect of enalapril, is not dose-dependent within the single dose range of 2.5-20 mg.


Effects of nicotine vary across two auditory evoked potentials in the mouse.
Schizophrenia patients display sensory processing deficits, reduced alpha7-nicotine receptor expression, and increased incidence of smoking, prompting investigation of nicotine receptor agonists as possible treatments. We evaluated the effects of acute and chronic nicotine, using an animal model that incorporates genetic variation for sensory processing and nicotine sensitivity. C57BL/6J and DBA/2Hsd mice received 2 weeks of 4.2 mg/kg chronic nicotine or saline. Auditory evoked potentials were recorded before and after acute nicotine injection of 1.05 mg/kg on day 14, with a paired-click paradigm (S1/S2). Amplitude and gating of the P20 and N40 were compared between conditions. Acute nicotine increased the amplitude and gating of the P20 and decreased the amplitude and gating of the N40 across all groups, primarily by acting on S1. Chronic nicotine attenuated the effects of acute nicotine on the N40. Our data support the notion that the mouse P20 shares pharmacological response properties with the human P50. In addition, findings suggest that nicotine might increase the initial sensory response (S1), with a resulting improvement in gating of some components.


Watch what I do, not what I say I do: Computer-based avatars to assess behavioral inhibition, a vulnerability factor for anxiety disorders.
Behavioral inhibition (BI), a tendency to withdraw from or avoid novel social and non-social situations, is a personality trait which can confer risk for anxiety disorders. Like many personality traits, BI is often assessed via self-report questionnaires where respondents rate themselves for frequency of certain behaviors or feelings. However, questionnaires have inherent limitations, particularly in psychiatric populations where there may be unawareness of deficit. A viable alternative may be virtual environments, in which the participant guides an on-screen "avatar" through a series of onscreen events meant to simulate real-world situations. Here, we report on initial development of such an assessment tool, involving several onscreen scenarios with choice points where the participant can select from response options corresponding to inhibited or uninhibited behaviors. In two experiments involving over 300 college students, scores on the computer-based task were strongly correlated with BI scores attained through self-report questionnaire (r>.780, p<.001); this relationship held regardless of participant gender and experience with computer games. The results suggest that virtual environments may hold promise as alternative formats for assessment of personality traits in populations unsuited to traditional paper-and-pencil questionnaire formats due to psychopathology, limited attention span, or poor vocabulary and/or literacy skills.


Deep Impact observations by OSIRIS onboard the Rosetta spacecraft.
The OSIRIS cameras (optical, spectroscopic, and infrared remote imaging system) onboard the European Space Agency's Rosetta spacecraft observed comet 9P/Tempel 1 for 17 days continuously around the time of NASA's Deep Impact mission. The cyanide-to-water production ratio was slightly enhanced in the impact cloud, compared with that of normal comet activity. Dust particles were flowing outward in the coma at >160 meters per second, accelerated by the gas. The slope of the brightness increase showed a dip about 200 seconds after the impact. Dust Afrho values before and long after the impact confirm the slight decrease of cometary activity. The dust-to-water mass ratio was much larger than 1.


Prevalence and predictors of female genital mutilation among infants in a semi urban community in northern Nigeria.
To determine the prevalence, predictors, of female genital mutilation (FGM) among infants and ascertain if their mothers knew what was done to them in Birnin Kudu northern Nigeria. Cross sectional study which utilised a pretested interviewer administered semi-structured questionnaire to assess occurrence of FGM with physical examination of the infants. Logistic regression analysis was used to assess the relative effect of determinants, after adjusting for other predictor variables. Of the 450 infants, 215(47.8%) (95% Confidence Interval [CI]: 43.1%-52.5%) had experienced one form of FGM. The ages at genital mutilation ranged from 1 to 50 days with a median of 4 days and interquartile range of 7 days. Maternal occupation, education and religion and type of facility accessed were significantly associated with occurrence of FGM in infants (p ≤ 0.05). After controlling for confounders, having a mother without formal education [AOR = 6.39 and 95% CI = 3.99-10.23] (p = 0.001) and one who was employed [Adjusted odds ratio (AOR) = 2.89 and 95% CI = 1.66-5.03] (p = 0.001) increased the likelihood of infant FGM remarkably while utilising tertiary institution for health care reduced the risk by about half [AOR = 0.49 and 95% CI = 0.26-0.92] (p = 0.03). Of the 215 infants that had undergone FGM, there was correlation between the reported and the observed forms of FGM in 16 (7.4%) of the cases. The prevalence of FGM is high with mothers' educational status, type of health facility utilised and occupational status being predictors of FGM among infants in Birnin Kudu. Majority of the mothers are not aware of what was done. Strategies aimed at discouraging this dangerous practice in the community should include female education, involvement of the men as husbands, fathers, traditional and religious leaders.


Effect of PRDX6 gene polymorphism on susceptibility to chronic obstructive pulmonary disease in the Chinese Han population.
To explore the relationship of peroxiredoxin6 (PRDX6) tag-single nucleotide polymorphisms (SNPs) with susceptibility to chronic obstructive pulmonary disease (COPD) in the Chinese Han population. A total of 502 patients with COPD and 481 healthy controls from nine hospitals in China were enrolled in this study. The PRDX6 tag-SNPs were identified by linkage disequilibrium (LD) analysis in 30 healthy controls. The associations between identified tag-SNPs and COPD risk were further evaluated. Four PRDX6 tag-SNPs, including rs7314, rs34619706, rs33951697, and rs4382766, were identified in 30 healthy controls. Moreover, in the allele model, there was no statistical difference in locus in PRDX6 between patients with COPD and healthy controls (P > 0.05). However, in the recessive model, rs33951697 locus in PRDX6 gene carrier with T/T had an increased risk of COPD (odds ratio [OR] = 2.59, 95% CI = 1.06-6.33, P = 0.028). Furthermore, in the relevance analysis between genetic polymorphisms and smoking behavior and lung function indexes, we found that the number of smoked cigarettes per day and FEV1/FVC differed among different genotypes of PRDX6, rs4382766, and rs7314 (P < 0.05). PRDX6 gene polymorphism with smoking status may contribute to the etiology of COPD in the Chinese Han population.


Indications for chlororespiration in relation to light regime in the marine diatom Thalassiosira weissflogii.
The marine diatom Thalassiosira weissflogii was cultured under a light regime simulating the daily rise and fall of the sun. The light regime caused a daily cycle in non-photochemical quenching. Remarkable were the changes in fluorescence directly after a light-to-dark transition that occurred in addition to the changes induced by non-photochemical quenching. A transient non-photochemical reduction of PQ and of Q(A) was indicated by a transient increase in apparent F(o) and by changes in the shape of the fluorescence induction curve. The observed changes developed approximately the first 100-120 s after a light-to-dark transition and could be reversed by the application of far-red illumination. Chlororespiration is thought to cause the reduction of PQ and, as the PQ-pool is in equilibrium with Q(A), also a reduction of Q(A). The function and ecological relevance of chlororespiration are discussed.


Neuroprotective effects of a Rhodiola crenulata extract on amyloid-β peptides (Aβ1-42) -induced cognitive deficits in rat models of Alzheimer's disease.
Rhodiola crenulata has been wildly used as a healthy food, antidepressant and antifatigue for many years in China. Recent studies suggested that Rhodiola crenulata extract (RCE) has cognitive protective effects in the treatment of Alzheimer's disease (AD). To assess the protective effects of RCE on cognitive deficits and clarify its therapeutic mechanisms in Aβ1-42 -induced rat models of AD. RCE was prepared by freeze-drying technology. Their protective effects on Aβ1-42-induced rat models of AD and the preliminary therapeutic mechanisms were studied. The Y maze test and Morris water maze (MWM) test were conducted to evaluate the learning and memory abilities of the rats. Subsequently, biochemical assays, hematoxylin-eosin staining, immunohistochemistry and Western blotting were performed to elucidate the mechanisms. RCE significantly increased the spontaneous alternation (F (6, 111) = 8.165, p < 0.001), prolonged the swimming time (F (6, 111) = 20.143, p < 0.001) and decreased the escape latency in rat models of AD. In addition, RCE significantly increased the acetylcholine (Ach) level and the choline acetyl transferase (ChAT) activity (F (6, 34) = 6.033, p < 0.001; F (6, 34) = 6.958, p < 0.001, respectively), repaired the damage of hippocampus neurons and prevented Aβ formation in the hippocampus in Aβ1-42 injected rats. Moreover, RCE increased the superoxide dismutase (SOD) activity and decreased the malondialdehyde (MDA) level in cortex of Aβ1-42 injected rats (F (6, 34) = 5.097, p < 0.01; F (6, 34) = 2.907, p < 0.05, respectively), significantly reduced the expressions of p-tau (ser396) and induced the expressions of p-GSK3β (ser9) in hippocampus (F (6, 34) = 15.297, p < 0.001; F (6, 34) = 9.652, p < 0.001, respectively). Our findings demonstrated that RCE significantly alleviated the learning and memory deficits in the Aβ1-42-induced rat models of AD. The mechanisms involved its protection effects against cholinergic system deficiency, oxidative stress damage and GSK3β activation. RCE may be a potential therapeutic medicine with multi-targets to prevent the progression of cognitive deterioration in AD.


Serological study of leptospiral infections and endogenous uveitis among horses and ponies in the United Kingdom.
The prevalence of antibody titres to a range of 20 leptospira antigens in the serum of horses and ponies with no ophthalmic abnormalities and with ophthalmoscopic evidence of endogenous uveal inflammatory disease was determined using a microscopic agglutination technique. Titres against leptospira antigens were observed in 13 out of 138 (9.1 per cent) animals with no ophthalmic abnormalities, and in three out of 27 (11.1 per cent) animals with anterior uveitis. Serovar sejroe was common to all seropositive animals with anterior uveitis. The results show that leptospira infection is not a major factor in the aetiology of equine anterior uveitis in the UK, but suggests that the organism may be associated with some cases of recurrent anterior uveitis.


An evaluation of residential care for tetraplegics.
A total of 280 tetraplegics admitted to the National Spinal Injuries Centre between 1970--1975 were followed up. Sixty-five cases found to require residential care were examined.


Rebellious autophagy proteins bypass ATG8 lipidation, taking their own path to autophagic degradation.
LC3/GABARAP (hereafter ATG8) conjugation machineries have long been thought to play an essential role in autophagy by driving ATG8 lipidation on autophagosomal membranes. In this issue, Ohnstad et al (2020) describe an ATG8 lipidation bypass pathway which governs autophagy-dependent turnover of NBR1, highlighting that there is more than one road to autophagic degradation.


Embolization of isolated lumbar artery injuries in trauma patients.
The purpose of the study was to evaluate the angiographic findings and results of embolotherapy in the management of lumbar artery trauma. All patients with lumbar artery injury who underwent angiography and percutaneous embolization in a state trauma center within a 10-year period were retrospectively reviewed. Radiological information and procedural reports were reviewed to assess immediate angiographic findings and embolization results. Long-term clinical outcome was obtained by communication with the trauma physicians as well as with chart review. In a 10-year period, 255 trauma patients underwent abdominal aortography. Eleven of these patients (three women and eight men) suffered a lumbar artery injury. Angiography demonstrated active extravasation (in nine) and/or pseudoaneurysm (in four). Successful selective embolization of abnormal vessel(s) was performed in all patients. Coils were used in six patients, particles in one and gelfoam in five patients. Complications included one retroperitoneal abscess, which was treated successfully. One patient returned for embolization of an adjacent lumbar artery due to late pseudoaneurysm formation. In hemodynamically stable patients, selective embolization is a safe and effective method for immediate control of active extravasation, as well as to prevent future hemorrhage from an injured lumbar artery.


Synchronous Development of Hemiscrotal Tissue in the Orthotopic and Ectopic Locations in Association with other Urological Anomalies.
Ectopic scrotum is a rare form of congenital scrotal anomaly that is rarely encountered in pediatric surgical practice. Herein, we report an infant with a unilateral ectopic suprainguinal scrotum associated with undescended testis and multicystic dysplastic kidney. The case is reported in view of rarity of this anomaly in the general pediatric population.


Value-added oil and animal feed production from corn-ethanol stillage using the oleaginous fungus Mucor circinelloides.
This study highlights the potential of oleaginous fungus, Mucor circinelloides in adsorbing/assimilating oil and nutrients in thin stillage (TS), and producing lipid and protein-rich fungal biomass. Fungal cultivation on TS for 2 days in a 6-L airlift bioreactor, resulted in a 92% increase in oil yield from TS, and 20 g/L of fungal biomass (dry) with a lipid content of 46% (g of oil per 100g dry biomass). Reduction in suspended solids and soluble chemical oxygen demand (SCOD) in TS were 95% and 89%, respectively. The polyunsaturated fatty acids in fungal oil were 52% of total lipids. Fungal cells grown on Yeast Malt (YM) broth had a higher concentration of γ-linolenic acid (17 wt.%) than those grown on TS (1.4 wt.%). Supplementing TS with crude glycerol (10%, v/v) during the stationary growth phase led to a further 32% increase (from 46% to 61%) in cellular oil content.


Assessing Patient Satisfaction Following Sodium Glucose Co-Transporter 2 Inhibitor Treatment for Type 1 Diabetes Mellitus: A Prospective Study in Japan.
In Japan, several sodium glucose co-transporter 2 (SGLT2) inhibitors have been used for type 1 diabetes mellitus as an adjuvant therapy to insulin therapy; however, there are no clinical reports regarding the satisfaction of its use. Therefore, we conducted a survey among patients with type 1 diabetes undergoing treatment using an SGLT2 inhibitor. This is a single-arm open-label prospective study including 24 patients with type 1 diabetes who were to be initiated on ipragliflozin treatment between March and August 2019. All participants provided written informed consent. They completed the Diabetes Treatment Satisfaction Questionnaire (DTSQ) for the survey and 3 months of observation after the administration of an SGLT2 inhibitor (50 mg of ipragliflozin), and changes from baseline diabetes treatment satisfaction were evaluated using modified DTSQ scores (five-step evaluation) and were analyzed. The average score for each question on DTSQ significantly increased [mean (standard deviation); 0.25 (0.25) vs 0.83 (0.77), P = 0.004]. Approximately 75% of the patients perceived an improvement in glycemic control over short periods of time. Finally, 54.2% of patients were highly satisfied and would recommend the SGLT2 inhibitor treatment [0.0 (0.0) vs. 0.92 (1.32), P < 0.001]. After the administration of ipragliflozin, reductions in body weight [24.0 (2.9) vs. 23.4 (2.9) kg/m2, P = 0.002], total insulin [39.1 (12.9) vs. 34.3 (12.5) units, P = 0.013], and glycated hemoglobin [7.77 (0.97) vs. 7.40 (0.86) %, P = 0.013] were observed, without any severe side effects. Improvements in glycemic variability indexes were observed through flash glucose monitoring. SGLT2 inhibitors may improve clinical treatment satisfaction by improving glycemic variability in patients with type 1 diabetes mellitus, while not inducing severe side effects with careful use. This study is registered with the University Hospital Medical Information Network Clinical Trial Registry (UMIN000040487).


Value of laparoscopic microwave coagulation therapy for hepatocellular carcinoma in relation to tumor size and location.
The indications for laparoscopic microwave coagulation therapy (LMCT) for hepatocellular carcinoma (HCC) have not yet been adequately evaluated. This study investigated the value of LMCT in the treatment of HCC. Forty-three patients with liver cirrhosis (including five patients in Child Pugh grade C), with 56 HCC lesions, were enrolled in the study. When dynamic computed tomography (CT) showed a loss in HCC enhancement characteristics and a low concentration area after LMCT, a lesion was judged to have undergone complete necrosis. The rate of complete necrosis for lesions measuring 40 mm or less was significantly higher (P<0.01) than for those measuring 41 mm or more. The rate of complete necrosis for lesions located on the liver surface, excluding those located close to the gallbladder or in contact with the diaphragm, was also significantly higher (P<0.01) than for those situated deep within the liver. The outcome for lesions of 40 mm or less was favorable. Intra-abdominal hemorrhage occurred in two patients, pneumothorax in three, and hepatic infarction in one, all associated with LMCT. However, these patients did not suffer any sequelae of clinical significance. This study suggests that there is a strong indication for LMCT for HCCs measuring 40 mm or less in diameter and those located on the liver surface even if they are as large as 50 mm, but not for those located close to the gallbladder or in contact with the diaphragm. LMCT appears to be applicable in patients with impaired liver function.


Mu rhythm-based cursor control: an offline analysis.
To classify the EEG data recorded in mu rhythm-based cursor control experiments with 4 possible choices. The algorithm included preprocessing, feature extraction, and classification. Two spatial filters, common average reference and common spatial subspace decomposition, were used in preprocessing to improve the signal-to-noise ratio, and then two features were extracted based on the power spectrum and the time course of the mu rhythm respectively. A Fisher ratio was defined to select channels in feature extraction. A 2-dimensional linear classifier was trained for final classification. Two types of classifiers were trained for the training dataset. The uniform classifier gave a classification accuracy of 76.4%, and the classifier trained by leave-one-out method gave a classification accuracy of 74.4%, both higher than the online accuracy 69.5%. The uniform classifier was applied to the test dataset and the classification accuracy was 65.9%, lower than the online accuracy 73.2%. Spatial filtering can give a notable improvement in classification accuracy. The time course of the mu rhythm, as well as the power of the mu rhythm, shows difference between the 4 targets, and can contribute to the classification. The spatial filtering, feature extraction and channel selection methods in the algorithm will provide some practical suggestions for further study on the mu rhythm-based brain-computer interface.


Feeling Well and Having Good Numbers: Renal Patients' Encounter With Clinical Uncertainties and the Responsibility to "Live Well".
Individuals living with chronic kidney disease (CKD) must be mindful of their diet and exercise, take multiple medications, and deal with other compounding illnesses. We observed renal patients' encounters with health professionals at a renal clinic for tensions and gaps in patients' and health professionals' understandings of "living well" with CKD. We found that the renal patients at the clinic become emotionally invested in the fluctuations in the numbers on their blood work. Narrative practices of health professionals greatly affect how patients emotionally deal with the possibility of dialysis, transplant, death, or aging. Expectations to "live well" can become a moral burden to be a "good" patient. The gaps between the priorities of patients, their caregivers, and health professionals complicate the notion of "living well" with CKD. Trust, rapport and the practice of listening appear to have the greatest impact in addressing these gaps.


Nontuberculous Mycobacterial Infections in Cystic Fibrosis.
Nontuberculous mycobacteria (NTM) are important pathogens, with a longitudinal prevalence of up to 20% within the cystic fibrosis (CF) population. Diagnosis of NTM pulmonary disease in people with CF (pwCF) is challenging, as a majority have NTM infection that is transient or indolent, without evidence of clinical consequence. In addition, the radiographic and clinical manifestations of chronic coinfections with typical CF pathogens can overlap those of NTM, making diagnosis difficult. Comprehensive care of pwCF must be optimized to assess the true clinical impact of NTM and to improve response to treatment. Treatment requires prolonged, multidrug therapy that varies depending on NTM species, resistance pattern, and extent of disease. With a widespread use of highly effective modulator therapy (HEMT), clinical signs and symptoms of NTM disease may be less apparent, and sensitivity of sputum cultures further reduced. The development of a disease-specific approach to the diagnosis and treatment of NTM infection in pwCF is a research priority, as a lifelong strategy is needed for this high-risk population.


Proprioceptive effects on gait and postural stability through mechanical stimulation with an Internal and External Heel Wedge: An interventional single-arm study.
Previous studies have shown that the stimulation of the foot sole can provide important information about the body's position and locomotion. However, these studies do not clarify how the position of the mechanical stimulation on the foot sole affects the gait cycle. This interventional single-arm study aims to verify if the insertion of an Internal Heel Wedge (IHW) and External Heel Wedge (EHW) can modify the stabilometric and podobarometric variables, the functional changes during the gait cycle, the different responses between the dominating lower limb and the non-dominating lower limb, and the potential temporal summations of the proprioceptive stimulation. Twenty-three healthy subjects (age 31 ± 5 years; weight 62 ± 1 kg; height 168±6 cm), with a right dominating lower limb, were recruited. The IHW and EHW were created out of half-moon-shaped cork pieces having a 1.5 mm thickness, 6 cm length and 3 cm height. The sequence of tests foresaw trials without IHW or EHW (Baseline), trials with IHW or EHW (Acute), trials after an adaptation period of 15 min on a treadmill with IHW or EHW (after 15'). Data showed statistically significant variations in the Step Rate, Duration of the cycle of the left step and Single Right Support phase for the IHW, Duration Single Right support and Single Left Support phase for the EHW. Data showed that a thin proprioceptive stimulation of the plantar arch was enough to induce changes in the gait cycle and that, upon changing the position of the proprioceptive stimulation, the functional response of the feet was inverted. These results can help health professionals provide a correct interpretation of the clinical data during follow-ups, avoiding undesirable and harmful effects on the patients' recovery.


Modulation of spinal excitability during observation of bipedal locomotion.
This study investigated whether a mirror mechanism exists for bipedal locomotion. We employed the soleus (plantar flexor) Hoffman reflex to investigate corticospinal excitability at the spinal level during observation of bipedal locomotion. The differential amplitude modulation of the left soleus Hoffman reflex during observation of bipedal heel-stepping (plantar dorsiflexion) (324+/-53 microV), standing still (383+/-60 microV), and bipedal toe-stepping (plantar flexion) (419+/-53 microV) reached significance (P < 0.05). The observation of bipedal toe-stepping produced a greater increase in spinal excitability than the observation of bipedal heel-stepping. These findings support the suggestion that there is a mirror mechanism for bipedal locomotion and they demonstrate that spinal excitability for observation of bipedal locomotion mirrors that for execution of bipedal locomotion.


Looking towards label-free biomolecular interaction analysis in a high-throughput format: a review of new surface plasmon resonance technologies.
Surface plasmon resonance (SPR) biosensors have enabled a wide range of applications in which researchers can monitor biomolecular interactions in real time. Owing to the fact that SPR can provide affinity and kinetic data, unique features in applications ranging from protein-peptide interaction analysis to cellular ligation experiments have been demonstrated. Although SPR has historically been limited by its throughput, new methods are emerging that allow for the simultaneous analysis of many thousands of interactions. When coupled with new protein array technologies, high-throughput SPR methods give users new and improved methods to analyze pathways, screen drug candidates and monitor protein-protein interactions.


Extracting multiple interacting root systems using X-ray microcomputed tomography.
Root system interactions and competition for resources are active areas of research that contribute to our understanding of how roots perceive and react to environmental conditions. Recent research has shown this complex suite of processes can now be observed in a natural environment (i.e. soil) through the use of X-ray microcomputed tomography (μCT), which allows non-destructive analysis of plant root systems. Due to their similar X-ray attenuation coefficients and densities, the roots of different plants appear as similar greyscale intensity values in μCT image data. Unless they are manually and carefully traced, it has not previously been possible to automatically label and separate different root systems grown in the same soil environment. We present a technique, based on a visual tracking approach, which exploits knowledge of the shape of root cross-sections to automatically recover from X-ray μCT data three-dimensional descriptions of multiple, interacting root architectures growing in soil. The method was evaluated on both simulated root data and real images of two interacting winter wheat Cordiale (Triticumaestivum L.) plants grown in a single soil column, demonstrating that it is possible to automatically segment different root systems from within the same soil sample. This work supports the automatic exploration of supportive and competitive foraging behaviour of plant root systems in natural soil environments.


Peroxisome Proliferator-Activated Receptor-gamma Is a Potent Target for Prevention and Treatment in Human Prostate and Testicular Cancer.
Peroxisome proliferator-activated receptor-gamma (PPAR)-gamma is a ligand-activated transcriptional factor belonging to steroid receptor superfamily. PPAR-gamma plays a role in both adipocyte differentiation and tumorigenesis. Up to date, PPAR-gamma is expressed in various cancer tissues, and PPAR-gamma ligand induces growth arrest of these cancer cells. In this study, we examined the expression of PPAR-gamma in prostate cancer (PC) and testicular cancer (TC) by RT-PCR and immunohistochemistry, and we also examined the effect of PPAR-gamma ligand in these cells by MTT assay, hoechest staining, and flow cytometry. PPAR-gamma expression was significantly more extensive and intense in malignant tissues than in normal tissues. PPAR-gamma ligand induced the reduction of malignant cell viability through apoptosis. These results demonstrated that the generated PPAR-gamma in PC and TC cells might play an important role in the tumorigenesis. PPAR-gamma may become a new target in the treatment of PC and TC.


Adolescent Social Stress Produces an Enduring Activation of the Rat Locus Coeruleus and Alters its Coherence with the Prefrontal Cortex.
Early life stress is associated with the development of psychiatric disorders. Because the locus coeruleus-norepinephrine (LC-NE) system is a major stress-response system that is implicated in psychopathology, developmental differences in the response of this system to stress may contribute to increased vulnerability. Here LC single unit and network activity were compared between adult and adolescent rats during resident-intruder stress. In some rats, LC and medial prefrontal cortex (mPFC) coherence was quantified. The initial stress tonically activated LC neurons and induced theta oscillations, while simultaneously decreasing LC auditory-evoked responses in both age groups. Stress increased LC-mPFC coherence within the theta range. With repeated exposures, adolescent LC neuronal and network activity remained elevated even in the absence of the stressor and were unresponsive to stressor presentation. In contrast, LC neurons of adult rats exposed to repeated social stress were relatively inhibited in the absence of the stressor and mounted robust responses upon stressor presentation. LC sensory-evoked responses were selectively blunted in adolescent rats exposed to repeated social stress. Finally, repeated stress decreased LC-mPFC coherence in the high frequency range (beta and gamma) while maintaining strong coherence in the theta range, selectively in adolescents. Together, these results suggest that adaptive mechanisms that promote stress recovery and maintain basal activity of the brain norepinephrine system in the absence of stress are not fully developed or are vulnerable stress-induced impairments in adolescence. The resulting sustained activation of the LC-NE system after repeated social stress may adversely impact cognition and future social behavior of adolescents.


Kyphotic deformity of the lumbar spine due to a monostotic fibrous dysplasia of the second lumbar vertebra: a case report and its surgical management.
Monostotic fibrous dysplasia (MFD) of the lumbar spine represents an exceedingly rare lesion. A 26-year-old patient presented with a progressive osteolytic lesion of the vertebral body L2 and the diagnosis of MFD. A minimally invasive left-sided eXtreme Lateral Interbody Fusion (XLIF) approach with resection of the vertebral body L2 with placement of a mesh cage was performed. No complications were observed perioperatively and the symptoms rapidly improved. Minimally invasive piecemeal resection with a combined dorsolateral approach showed a favorable clinical and radiological outcome and seems to be a safe and reliable technique for MFD.


Integrating chemical mutagenesis and whole-genome sequencing as a platform for forward and reverse genetic analysis of Chlamydia.
Gene inactivation by transposon insertion or allelic exchange is a powerful approach to probe gene function. Unfortunately, many microbes, including Chlamydia, are not amenable to routine molecular genetic manipulations. Here we describe an arrayed library of chemically induced mutants of the genetically intransigent pathogen Chlamydia trachomatis, in which all mutations have been identified by whole-genome sequencing, providing a platform for reverse genetic applications. An analysis of possible loss-of-function mutations in the collection uncovered plasticity in the central metabolic properties of this obligate intracellular pathogen. We also describe the use of the library in a forward genetic screen that identified InaC as a bacterial factor that binds host ARF and 14-3-3 proteins and modulates F-actin assembly and Golgi redistribution around the pathogenic vacuole. This work provides a robust platform for reverse and forward genetic approaches in Chlamydia and should serve as a valuable resource to the community.


Oral combined contraceptives induce liver mitochondrial reactive oxygen species and whole-body metabolic adaptations in female mice.
Compared to age-matched men, pre-menopausal women show greater resilience against cardiovascular disease (CVD), hepatic steatosis, diabetes and obesity - findings that are widely attributed to oestrogen. However, meta-analysis data suggest that current use of oral combined contraceptives (OC) is a risk factor for myocardial infarction, and OC use further compounds with metabolic disease risk factors to increase CVD susceptibility. While mitochondrial function in tissues such as the liver and skeletal muscle is an emerging mechanism by which oestrogen may confer its protection, effects of OC use on mitochondria and metabolism in the context of disease risk remain unexplored. To answer this question, female C57Bl/6J mice were fed a high fat diet and treated with vehicle or OCs for 3, 12 or 20 weeks (n = 6 to 12 per group) at a dose and ratio that mimic the human condition of cycle cessation in the low oestrogen, high progesterone stage. Liver and skeletal muscle mitochondrial function (respiratory capacity, H2 O2 , coupling) was measured along with clinical outcomes of cardiometabolic disease such as obesity, glucose tolerance, hepatic steatosis and aortic atherosclerosis. The main findings indicate that regardless of treatment duration, OCs robustly increase hepatic mitochondrial H2 O2 levels, likely due to diminished antioxidant capacity, but have no impact on muscle mitochondrial H2 O2 . Furthermore, OC-treated mice had lower adiposity and hepatic triglyceride content compared to control mice despite reduced wheel running, spontaneous physical activity and total energy expenditure. Together, these studies describe tissue-specific effects of OC use on mitochondria as well as variable impacts on markers of metabolic disease susceptibility. KEY POINTS: Oestrogen loss in women increases risk for cardiometabolic diseases, a link that has been partially attributed to negative impacts on mitochondria and energy metabolism. To study the effect of oral combined contraceptives (OCs) on hepatic and skeletal muscle mitochondria and whole-body energy metabolism, we used an animal model of OCs which mimics the human condition of cessation of hormonal cycling in the low oestrogen, high progesterone state. OC-treated mice have increased hepatic mitochondrial oxidative stress and decreased physical activity and energy expenditure, despite displaying lower adiposity and liver fat at this time point. These pre-clinical data reveal tissue-specific effects of OCs that likely underlie the clinical findings of increased cardiometabolic disease in women who use OCs compared to non-users, when matched for obesity.