Ovarian cancers overexpress the antimicrobial protein hCAP-18 and its derivative LL-37 increases ovarian cancer cell proliferation and invasion.
The role of the pro-inflammatory peptide, LL-37, and its pro-form, human cationic antimicrobial protein 18 (hCAP-18), in cancer development and progression is poorly understood. In damaged and inflamed tissue, LL-37 functions as a chemoattractant, mitogen and pro-angiogenic factor suggesting that the peptide may potentiate tumor progression. The aim of this study was to characterize the distribution of hCAP-18/LL-37 in normal and cancerous ovarian tissue and to examine the effects of LL-37 on ovarian cancer cells. Expression of hCAP-18/LL-37 was localized to immune and granulosa cells of normal ovarian tissue. By contrast, ovarian tumors displayed significantly higher levels of hCAP-18/LL-37 where expression was observed in tumor and stromal cells. Protein expression was statistically compared to the degree of immune cell infiltration and microvessel density in epithelial-derived ovarian tumors and a significant correlation was observed for both. It was demonstrated that ovarian tumor tissue lysates and ovarian cancer cell lines express hCAP-18/LL-37. Treatment of ovarian cancer cell lines with recombinant LL-37 stimulated proliferation, chemotaxis, invasion and matrix metalloproteinase expression. These data demonstrate for the first time that hCAP-18/LL-37 is significantly overexpressed in ovarian tumors and suggest LL-37 may contribute to ovarian tumorigenesis through direct stimulation of tumor cells, initiation of angiogenesis and recruitment of immune cells. These data provide further evidence of the existing relationship between pro-inflammatory molecules and ovarian cancer progression.


Bacillus naphthovorans sp. nov. from oil-contaminated tropical marine sediments and its role in naphthalene biodegradation.
A Bacillus sp., designated as strain MN-003, was isolated as the dominant cultivatable naphthalene-degrading organism from oil-contaminated tropical marine sediments. Strain MN-003 is strictly aerobic, rod-shaped, Gram-positive, catalase positive, oxidase negative, and forms endospores. Strain MN-003 grew at salinities ranging from 0.28 to 7.00% and temperatures ranging from 15 to 41 degrees C. Phylogenetic analyses reveal that strain MN-003 is most similar to Bacillus sp. VAN14, with a 16S rRNA sequence identity of 97.9%. Based on taxonomic and 16S rRNA data, strain MN-003 was named Bacillus naphthovorans sp. nov. When grown with naphthalene as sole carbon source, strain MN-003 had a maximal specific growth rate (mu(max)) of 0.32 +/- 0.03 h(-1), and a half-saturation constant (K(S)) of 22.3 +/-4.2 microM. A batch study of the tropical marine sediments enriched with naphthalene showed that cells of the Bacillus genus grew to become dominant members of the microbial community. The bacilli comprised 39.5 +/- 6.5% of the microbial fraction after 20 days of enrichment.


Fine needle aspiration cytology of lymph nodes in breast cancer follow-up is a feasible alternative to watchful waiting and to histology.
Early detection of loco-regional breast cancer recurrence improves patients' overall survival, as treatment can be initiated or active treatment can be changed. If a suspicious lymph node is diagnosed during a follow-up exam, surgical excision is often performed. The aim of this study was to evaluate the diagnostic performance of the minor invasive ultrasound-guided fine-needle aspiration cytology (FNAC) in sonomorphologically suspicious lymph nodes in breast cancer follow-up. Between April 2010 and November 2012, we performed ultrasound-guided FNAC in 38 sonographically suspicious lymph nodes of 37 breast cancer follow-up patients. Cytological specimens were evaluated if the sample material was sufficient for diagnosis and if they contained cancer cells. Patients with negative cytology were followed up clinically and sonographically. To evaluate the diagnostic performance we calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for physical examination, the different sonomorphological malignancy criteria and FNAC. In 36/38 (94.7 %) lymph nodes, the pathologist had enough material to establish a final diagnosis; in 2/38 (5.3 %) lymph nodes, the probe material was non-evaluable during cytology, these 2 were excluded from further statistical evaluation. Cytology revealed malignancy in 21 lymph nodes and showed no evidence for malignancy in 15 lymph nodes. There was no evidence for malignant disease in follow-up exams in the 15 cytologically benign lymph nodes with an average follow-up time of 3 years. The diagnostic performances of physical examination and FNAC were: Sensitivity 52/100 %, specificity 88/100 %, PPV 85/100 %, NPV 60/100 %, respectively. Our preliminary results show that FNAC is a safe and fast diagnostic approach for the evaluation of suspicious lymph nodes in the follow-up of patients with breast cancer and, thus, together with follow-up represents a feasible alternative to surgery.


Identification and management of acute alcohol intoxication.
Acute alcohol intoxication (AAI) is a harmful clinical condition, potentially life-threatening, secondary to the intake of large amounts of alcohol. Clinical manifestations of AAI are characterized by behavioural and neurological symptoms, even if its effects involve several organs and apparatus. Moreover, severe alcohol intoxication can produce a global neurological impairment leading to autonomic dysfunction, respiratory depression, coma and cardiac arrest. The evaluation of blood alcohol concentrations (BAC) is useful to confirm the suspicion of intoxication, both for clinical and legal reasons. Most of patients with AAI are referred to Emergency Departments due to behavioural, social, traumatic or clinical complications. Patient's stabilization is the first step in the management of AAI, in order to support vital functions and to prevent complications. Metadoxine represents a useful drug to increase ethanol metabolism and elimination. Given that AAI could represent a sentinel event of chronic alcohol abuse, patients presenting with acute intoxication should be screened for the presence of an underlying alcohol use disorder and referred to and an alcohol addiction unit to start a multidisciplinary treatment to achieve long term alcohol abstinence. The present review will focus on clinical features, diagnostic criteria and treatment strategies of AAI.


Interstitial brachytherapy for intracranial metastases.
In large medical centers, the availability of radiosurgery has relegated brachytherapy to a lesser role in the treatment of newly diagnosed solitary brain metastases. However, the treatment planning in radiosurgery is complex, and in some case the hardware is prohibitively expensive; low or high dose rate brachytherapy requires only a stereotactic frame, commercially available software, and encapsulated radionuclides or newer tiny linear accelerators. Interstitial brachytherapy also remains an option for the treatment of recurrent solitary metastases when other forms of treatment have failed. This article reviews the radiobiology of low and high dose rate interstitial brachytherapy, the University of California San Francisco (UCSF) results using iodine-125 implants, and early experience with the photon radiosurgery system (PRS) at Massachusetts General Hospital for the treatment of brain metastases.


Falls Efficacy Scale-International: Exploring psychometric properties with adult day care users.
The majority of validation studies with the Falls Efficacy Scale-International (FES-I) are conducted with independent community-dwelling older people, which limits extrapolation to more vulnerable people, namely those receiving adult day care services. This study aimed to analyse the psychometric properties of the FES-I in terms of internal consistency, test-retest reliability, concurrent and convergent validity with users of adult day care centres. A cross-sectional study was conducted. Data collection included a socio-demographic questionnaire, the FES-I, the Activities-specific Balance Confidence Scale (ABC), the Hospital Anxiety and Depression Scale (HADS), the Timed Up and Go test (TUG) and the Five Times Sit to Stand Test (FTSST). Descriptive and inferential analyses were performed. A total of 100 users of adult day care centres (81.94 ± 6.43 years old; 77% female) have participated. The FES-I had excellent internal consistency (α = 0.970) and test-retest reliability (ICC2,1 = 0.979). A significant negative correlation was found between the FES-I and the ABC (rs = -0.828; p < 0.001), suggesting good concurrent validity. FES-I scores were significantly higher among those who were female, had less educational levels and reported having fear of falling. Significant correlations were found between FES-I and age (rs = 0.217; p < 0.05), HADS-Anxiety (rs = 0.486; p < 0.001), HADS-Depression (rs = 0.658; p < 0.001), TUG (rs = 0.653; p < 0.001) and FTSST (rs = 0.635; p < 0.001), indicating acceptable convergent validity. The FES-I is a reliable and valid instrument to assess concern about falling among users of adult day care centres. The findings are highly comparable with those previously found for non-users. FES-I can be used to prevent risk of falls in this type of care settings.


Cluster-randomized trials of cancer screening interventions: Has use of appropriate statistical methods increased over time?
In a cluster randomized trial, groups of individuals (e.g., clinics, schools) are randomized to conditions. The design and analysis of cluster randomized trials can require more care than individually randomized trials. Past reviews have noted deficiencies in the use of appropriate statistical methods for such trials. We reviewed cluster randomized trials of cancer screening interventions published 1995-2019 to determine whether appropriate statistical methods had been used for sample size calculation and outcome analysis and whether they reported intraclass correlation coefficient (ICC) values. This work expanded a previous review of articles published 1995-2010. Our search identified 88 articles published 1995-2020 that reported outcomes of cluster randomized trials of breast, cervix, and colorectal cancer screening interventions. There was increased reporting of the trials' sample size calculations over time, with the percentage increasing from 31% in 1995-2004 to 77% in 2014-2019. However, the percentage of calculations failing to account for cluster randomization did not change over time and was 17% of studies in 2014-2019. There was a nonsignificant trend towards increased use of outcome analysis methods that accounted for the cluster randomized design. However, in lower impact journals, use of appropriate analysis methods was only 80% in 2014-2019. Only 33% of studies reported ICC values in 2014-2019. For cluster randomized trials with cancer screening outcomes, there have been improvements in the reporting of sample size calculations but methodological and reporting deficiencies persist. Efforts to disseminate, adopt and report the use of appropriate statistical methodologies are still needed.


[Expression of mRNA of matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase after cardiopulmonary resuscitation for asphyxial cardiac arrest in rat].
To study the change in mRNA expression of matrix metalloproteinase (MMPs) and tissue inhibitor-1 of matrix metalloproteinase (TIMP-1) in brain after cardiopulmonary resuscitation (CPR) for asphyxial cardiac arrest in rat. The animal model of cardiac arrest was reproduced by clamping endotracheal tube at the expiration. Eighty male SD rats were randomly divided into two groups: control group and resuscitation group, and they were again divided into 0, 0.5, 3, 6, 9 hours subgroups (n=8). Evans blue content and mRNA expressions of MMPs and TIMP-1 in the brain after CPR were determined respectively. The mRNA expression of MMP-9 and TIMP-1 was up-regulated 3 hours after restoration of spontaneous circulation (ROSC). At 6 hours after ROSC, they were markedly high, and the ratio of MMP-9/TIMP-1 was higher too. The mRNA expression of MMP-2 showed no significant change at 9 hours after ROSC. The mRNA expression of MMP-9 and TIMP-1 and MMP-9/TIMP-1 are increased at early stage after CPR, but the mRNA expression of MMP-2 shows no significant change.


Characteristics of violence among high-risk adolescent girls.
Recent evidence demonstrates increasing rates of involvement with violence among adolescent girls. The objective of this study was to describe the types and sources of violence experienced within social contexts of adolescent girls at high risk for pregnancy. Qualitative data for this analysis are drawn from intervention summary reports of 116 girls participating in Prime Time, a youth development intervention for adolescent girls. Descriptive content analysis techniques were used to identify types and sources of violence experienced by girls within their daily contexts. Types of violence included physical fighting, witnessing violence, physical abuse, gang-related violence, verbal fighting, verbal abuse, and sexual abuse. Sources of violence included family, peers and friends, romantic partners, community violence, and self-perpetrated violence. Many girls in this study experienced violence in multiple contexts. It is imperative that efforts to assess and prevent violence among adolescent girls include paying attention to the social contexts in which these adolescents live.


A new Afrolimnophila Alexander from Europe (Diptera: Limoniidae).
A new species of the genus Afrolimnophila Alexander, 1956 is described from Europe, A. erhanae sp. nov., and its wing and male terminalia are illustrated. A key to West Palearctic species of the genus is appended.


The pentose catabolic pathway of the rice-blast fungus Magnaporthe oryzae involves a novel pentose reductase restricted to few fungal species.
A gene (MoPRD1), related to xylose reductases, was identified in Magnaporthe oryzae. Recombinant MoPRD1 displays its highest specific reductase activity toward L-arabinose and D-xylose. Km and Vmax values using L-arabinose and D-xylose are similar. MoPRD1 was highly overexpressed 2-8h after transfer of mycelium to D-xylose or L-arabinose, compared to D-glucose. Therefore, we conclude that MoPDR1 is a novel pentose reductase, which combines the activities and expression patterns of fungal L-arabinose and D-xylose reductases. Phylogenetic analysis shows that PRD1 defines a novel family of pentose reductases related to fungal D-xylose reductases, but distinct from fungal L-arabinose reductases. The presence of PRD1, L-arabinose and D-xylose reductases encoding genes in a given species is variable and likely related to their life style.


Leaf fall as a source of leaf miner mortality.
Leaf miner deaths resulting from the death of their leaves were assessd by collecting falling leaves of holm oak and beech. The Phyllonorycter mines thus captured were examined to ascertain the cause of death. For both mining species the mortality from leaf shedding accounted for less than 2.8% of the mining cohorts. It is argued that the level of mortality is insufficient for population regulation, as has been previously suggested.


Accelerated skills preparation and assessment for senior medical students entering surgical internship.
Skills training plays an increasing role in residency training. Few medical schools have skills courses for senior students entering surgical residency. A skills course for 4(th)-year medical students matched in a surgical specialty was conducted in 2006 and 2007 during 7 weekly 3-hour sessions. Topics included suturing, knot tying, procedural skills (eg, chest tube insertion), laparoscopic skills, use of energy devices, and on-call management problems. Materials for outside practice were provided. Pre- and postcourse assessment of suturing skills was performed; laparoscopic skills were assessed postcourse using the Society of American Gastrointestinal and Endoscopic Surgeons' Fundamentals of Laparoscopic Surgery program. Students' perceived preparedness for internship was assessed by survey (1 to 5 Likert scale). Data are mean +/- SD and statistical analyses were performed. Thirty-one 4(th)-year students were enrolled. Pre- versus postcourse surveys of 45 domains related to acute patient management and technical and procedural skills indicated an improved perception of preparedness for internship overall (mean pre versus post) for 28 questions (p < 0.05). Students rated course relevance as "highly useful" (4.8 +/- 0.5) and their ability to complete skills as "markedly improved" (4.5 +/- 0.6). Suturing and knot-tying skills showed substantial time improvement pre- versus postcourse for 4 of 5 tasks: simple interrupted suturing (283 +/- 73 versus 243 +/- 52 seconds), subcuticular suturing (385 +/- 132 versus 274 +/- 80 seconds), 1-handed knot tying (73 +/- 33 versus 58 +/- 22 seconds), and tying in a restricted space (54 +/- 18 versus 44 +/- 16 seconds) (p < 0.02). Only 2-handed knot tying did not change substantially (65 +/- 24 versus 59 +/- 24 seconds). Of 13 students who took the Fundamentals of Laparoscopic Surgery skills test, 5 passed all 5 components and 3 passed 4 of 5 components. Skills instruction for senior students entering surgical internship results in a higher perception of preparedness and improved skills performance. Medical schools should consider integrating skills courses into the 4(th)-year curriculum to better prepare students for surgical residency.


Tat-conjugated PAMAM dendrimers as delivery agents for antisense and siRNA oligonucleotides.
PAMAM G5 dendrimer (P) was conjugated to Tat peptide (T), a cell penetrating peptide, in search of an efficient cellular delivery vehicle for antisense and siRNA oligonucleotides. PAMAM G5 dendrimer was reacted with 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionic acid, sulfosuccinimidyl ester, sodium salt (BODIPY) for visualization to yield the conjugate BP. Bifunctional sulfosuccinimidyl 6-[alpha-methyl-alpha-(2-pyridyldithio)toluamido]hexanoate (sulfo-LC-SMPT) was then used to conjugate primary amino groups of BP to cysteine derivatized Tat peptide to give the designed conjugate, BPT. This conjugate was complexed with antisense and siRNA oligonucleotides designed to inhibit MDR1 gene expression. NIH 3T3 MDR cells were used for the evaluation of biological activity of the conjugate. Both antisense and siRNA readily formed complexes with the synthesized BPT, introduced into NIH 3T3 MDR cells, and primarily accumulated in intracellular vesicles. MDR1 gene expression was partially inhibited by the antisense-BPT complex and weakly inhibited by the siRNA-BPT complex when both were tested at nontoxic levels of dendrimer. Conjugation with Tat peptide did not improve the delivery efficiency of the dendrimer. Dendrimer-oligonucleotide complexes were moderately effective for delivery of antisense and only poorly effective for delivery of siRNA. Conjugation of the dendrimer with the Tat cell penetrating peptide failed to further enhance the effectiveness of the dendrimer.


Orexin fibers form appositions with Fos expressing neuropeptide-Y cells in the grass rat intergeniculate leaflet.
Neuropeptide-Y (NPY) cells in the intergeniculate leaflet (IGL) are known to modulate effects of arousal on the mammalian circadian system. However, the route through which this information reaches the IGL has not been established. Here, we provide evidence that the orexins (hypocretins) are uniquely positioned as a potential source of activity state feedback to the IGL in the grass rat, Arvicanthis niloticus. Specifically, many NPY cells in the grass rat IGL exhibit orexin-A (OXA) fiber appositions. Furthermore, NPY cells contacted by OXA fibers are significantly more likely to express Fos during nocturnal wheel running than are NPY cells without such contacts (P < 0.001).


The safety and efficacy of terazosin in the treatment of essential hypertension in blacks.
Terazosin, a new selective alpha 1-adrenergic receptor antagonist, has been found to be an effective antihypertensive agent. In a series of studies, the safety and efficacy of terazosin, alone and in combination with other antihypertensive agents, were evaluated in 1180 black patients with mild to moderate essential hypertension. Terazosin was effective in lowering blood pressure when administered alone (in dosages of 1 to 80 mg/day) and when prescribed (in dosages of 1 to 20 mg/day) in combination with other antihypertensive agents. In elderly black patients, terazosin, 1 to 10 mg daily, was as effective in lowering blood pressure as propranolol (40 to 120 mg twice daily). Changes (mean +/- SE) in sitting diastolic blood pressure from baseline were -8.1 +/- 1.4 mm Hg for terazosin and -5.0 +/- 1.5 mm Hg for propranolol. Terazosin (5 mg) combined with methyclothiazide (2.5 to 5 mg) produced a significantly greater (p less than 0.01) antihypertensive effect than that of terazosin alone. Changes (mean +/- SE) in standing diastolic blood pressure from baseline were -7.9 +/- 2.0 mm Hg for terazosin alone, -15.1 +/- 2.1 mm Hg for terazosin plus 2.5 mg of methyclothiazide, and -15.0 +/- 2.0 mm Hg for terazosin plus 5 mg of methyclothiazide. Terazosin had a favorable effect on serum lipid levels and appeared to compensate for the negative lipid effects associated with diuretics and beta-blockers when used in combination with these agents. Terazosin, alone and combined with other antihypertensive agents, was well tolerated with minimal side effects in black hypertensive patients.


Saccharin effects on morphine-induced temperature change in rats.
The effects of saccharin on morphine-induced temperature change was examined in Long-Evans rats. Rats were given free access to 0.15% saccharin for 15 days, followed by saccharin deprivation for 9 days. Saccharin was then returned to one group, while a second group received water. All rats were then injected with morphine sulfate (2 mg/kg), and postinjection temperatures were assessed over 75 min. The results showed that saccharin enhanced the biphasic effects of morphine by significantly increasing the hypothermic phase. The findings support the view that sweet substances influence endogenous opioid release.


Design and Structure of an Engineered Disulfide-Stabilized Influenza Virus Hemagglutinin Trimer.
We engineered a disulfide-stabilized influenza virus hemagglutinin (HA) trimer, termed HA3-SS, by introducing cysteine residues into the HA stem to covalently bridge the three protomers. HA3-SS has increased thermostability compared to wild-type HA, and binding of head- and stem-targeted antibodies (Abs) is preserved; only minor structural changes are found in the vicinity of the additional disulfide. This platform has been applied to H1 and H3 HAs and provides prospects for design of intact, stabilized influenza virus HA immunogens.


[Isolation and analysis of oxalic acid insensitive mutant of Arabidopsis thaliana].
Oxalic acid (OA) is inhibitory to many fungal plant pathogens. To further characterize the molecular mechanism of OA involved in fungal pathogenesis, OA insensitive mutants were screened from a chemical inducible Arabidopsis mutant library (about 6000 lines) using MS medium (calcium free) containing 1.2 mmol/L OA and 10 micromol/L estradiol. Harvested putative mutants were collected separately. Individual lines of mutants were screened again on modified MS medium containing OA. Mutants D33, D74, D154, D282 and D630 with enhanced OA resistance were obtained. The T-DNA flanking sequences were amplified by TAIL-PCR. The sequences were blasted against TAIR database. The result indicated that the T-DNA of mutant D33 was inserted between At2g39720 (zinc finger) and At2g39730 (Rubisco activase), and the T-DNA junctions of the other four mutants were the same, all inserted in the same site of the first intron of At5g10450 (14-3-3 protein GF14 lambda).


At the bench: the key role of PK-PD modelling in enabling the early discovery of biologic therapies.
Pharmacokinetic-pharmacodynamic (PK-PD) modelling is already used extensively in pre-clinical and clinical drug development to characterize drug candidates quantitatively, aid go/no-go decisions and to inform future trial design and optimal dosing regimens. Less well known, although arguably as powerful, is its application at the earliest stages of drug development, at target selection and lead selection, where these same techniques can be used to predict and so bring forward drug candidates with the necessary characteristics or, for unachievable requirements, allow the abandonment of the programme for the minimum spend of time and cost. We consider three examples that illustrate the power of the application of modelling at this early stage. We start with the simple case of determining the optimal characteristics for a monoclonal antibody against a soluble ligand with its application to the investment decision for the development of best-in-class compounds. This is extended to the more complex situation of the target protein having an endogenous, inhibitory binding protein. We then illustrate how using physiologically-based pharmacokinetic modelling enables the appropriate engineering and testing of biological therapeutics for optimal PK-PD characteristics. These examples illustrate how a minimal investment in modelling achieves orders of magnitude better returns in choosing the correct targets, mechanism of action and candidate characteristics to progress to clinical trials, streamlining drug development and delivering better medicines to patients.


Noninvasive skin imaging in esthetic medicine-Why do we need useful tools for evaluation of the esthetic procedures.
Despite the constant development of aesthetic medicine, there is still a lack of objective methods to assess the effectiveness of antiaging treatments and their impact on the skin. Histopathological examination of the skin section provides most of the key information about the condition of the skin, but it is an invasive procedure that requires a skin biopsy, which may be associated with the formation of a scar that is considered to be an aesthetic defect. Non-invasive imaging methods of the skin like dermoscopy, skin ultrasonography and reflectance confocal microscopy may be a useful solution. In this systematic review, we present the possible application of noninvasive skin imaging methods in esthetic medicine. The literature search was conducted via medical database (PubMed, Google Scholar). The research suggests the use of dermoscopy during laser therapy, for the targeted treatment of vascular lesions and appropriate adjustment of laser parameters. Skin ultrasonography, especially high-frequency ultrasonography, has been widely used in aesthetic medicine-during and after volumetric treatments and in the assessment of the effects of anti-cellulite therapies, treatments that correct discolorations and improve skin quality. Publications also highlight the importance of reflexive confocal microscopy in the evaluation of the results of anti-aging treatments using the fractional laser, moisturizing preparations or micro puncturing combined with hyaluronic acid injections. Non-invasive skin imaging methods are useful tools for pre- and postoperative assessment in aesthetic medicine and their wide application may help to objectively assess the impact of anti-aging procedures on the skin.


Smell or vision? The use of different sensory modalities in predator discrimination.
Theory predicts that animals should adjust their escape responses to the perceived predation risk. The information animals obtain about potential predation risk may differ qualitatively depending on the sensory modality by which a cue is perceived. For instance, olfactory cues may reveal better information about the presence or absence of threats, whereas visual information can reliably transmit the position and potential attack distance of a predator. While this suggests a differential use of information perceived through the two sensory channels, the relative importance of visual vs. olfactory cues when distinguishing between different predation threats is still poorly understood. Therefore, we exposed individuals of the cooperatively breeding cichlid Neolamprologus pulcher to a standardized threat stimulus combined with either predator or non-predator cues presented either visually or chemically. We predicted that flight responses towards a threat stimulus are more pronounced if cues of dangerous rather than harmless heterospecifics are presented and that N. pulcher, being an aquatic species, relies more on olfaction when discriminating between dangerous and harmless heterospecifics. N. pulcher responded faster to the threat stimulus, reached a refuge faster and entered a refuge more likely when predator cues were perceived. Unexpectedly, the sensory modality used to perceive the cues did not affect the escape response or the duration of the recovery phase. This suggests that N. pulcher are able to discriminate heterospecific cues with similar acuity when using vision or olfaction. We discuss that this ability may be advantageous in aquatic environments where the visibility conditions strongly vary over time. The ability to rapidly discriminate between dangerous predators and harmless heterospecifics is crucial for the survival of prey animals. In seasonally fluctuating environment, sensory conditions may change over the year and may make the use of multiple sensory modalities for heterospecific discrimination highly beneficial. Here we compared the efficacy of visual and olfactory senses in the discrimination ability of the cooperatively breeding cichlid Neolamprologus pulcher. We presented individual fish with visual or olfactory cues of predators or harmless heterospecifics and recorded their flight response. When exposed to predator cues, individuals responded faster, reached a refuge faster and were more likely to enter the refuge. Unexpectedly, the olfactory and visual senses seemed to be equally efficient in this discrimination task, suggesting that seasonal variation of water conditions experienced by N. pulcher may necessitate the use of multiple sensory channels for the same task.


Bone morphogenetic protein-2 will be a novel biochemical marker in urinary tract infections and stone formation.
To investigate the role of bone morphogenetic protein-2 (BMP-2) in patients with urinary tract infection (UTI) and renal stone in relation to Tamm-Horsfall protein (THP) and osteopontin (OPN). ELISA kits were used to determine these markers in serum and urinary samples of 20 patients with UTI, 15 with renal stone and 10 controls. BMP-2 significantly increased in serum of patients who had UTI (P=0.05) and renal stone (P=0.01). In the case of UTI, serum BMP-2 at cutoff 44 pg/mL had sensitivity and specificity (92%, 80%), while cystatin C at cutoff 525 ng/mL showed sensitivity and specificity (85%, 91%). THP is a good predictor of renal diseases (P<0.001) by regression analysis. It is also the most sensitive urinary marker for UTI with sensitivity and specificity (94%, 75%) at cutoff 305 ng/mL. Combination of serum BMP-2 and cystatin C are more sensitive and accurate for early diagnosis of renal infection and damage.


Monoclonal antibodies against tetanus toxin and toxoid.
Monoclonal antibodies against tetanus toxin and its toxoid were produced by immunizing mice with toxoid or toxin. They were measured by an enzyme-linked immunosorbent assay (ELISA), by a toxin neutralization test in mice (in vivo prevention test), and by their ability to prevent binding of 125I-toxin to brain membranes or gangliosides (in vitro prevention test). Six monoclonal antibodies obtained by immunization with toxoid (anti-toxoid 1-6) were investigated in more detail. They belonged to IgG class 1. Three of them (anti-toxoid 1, 2 and 3) recognized both toxoid and toxin as well as fragment B and the light chain of toxin, but not fragment C. Two other antibodies (anti-toxoid 4 and 5) were directed against toxoid only. Neither of them prevented toxin action in vitro or in vivo. Anti-toxoid 6 recognized toxin, toxoid and fragment C, but not light chain, and prevented toxin action in vitro and in vivo. Immunization against toxin was initiated with a toxin-antitoxin complex and boosted with toxin. We studied six antibodies in more detail, all of IgG type 2. Their KD against 125I-tetanus toxin varied from 10(-9) to 10(-10) M. Anti-toxin 2 recognized toxin, toxoid, light chain and fragment B, but not fragment C. The others reacted with toxin, toxoid and fragment C, but not with light chain or fragment B. All of them prevented toxin action in vitro and in vivo. As calculated from the maximal extinction achieved in the ELISA, tetanus toxin combined with a maximum of two different antibody molecules from our set. Gel filtration data indicate that tetanus toxin reacts with monoclonal antibodies one by one. Compared with polyclonal antiserum, monoclonal antibodies yield flatter slopes in both in vitro and in vivo prevention tests. Thus, they cannot substitute for the polyclonal antibodies in clinical situations, and cannot be calibrated in international units.


An improved reversal technique from retrograde to antegrade femoral artery cannulation.
Converting retrograde femoral access to antegrade access may be required following diagnostic arteriography to perform an interventional procedure. This technical note describes a modification of a previously described technique that allows reliable catheter reversal which was successful in 27 attempted procedures. There were no complications.


Feasibility and Efficacy of Adjuvant Chemotherapy With Gemcitabine After Liver Transplantation for Perihilar Cholangiocarcinoma - A Multi-Center, Randomized, Controlled Trial (pro-duct001).
Liver transplantation (LT) is considered a therapeutic option for unresectable perihilar cholangiocarcinoma (PHC) within defined criteria. It remains uncertain whether patients can safely receive adjuvant chemotherapy after LT. We performed a prospective, multi-center, randomized, non-blinded two-arm trial (pro-duct001). Patients after LT for unresectable PHC within defined criteria were randomized to adjuvant gemcitabine (LT-Gem group) and LT alone (LT alone group). The primary objective was to investigate if adjuvant chemotherapy is feasible in ≥ 85% of patients after LT. The primary endpoint was the percentage of patients completing the 24 weeks course of adjuvant chemotherapy. Secondary endpoints included overall survival (OS) and disease-free (DFS), and complication rates. Twelve patients underwent LT for PHC, of which six (50%) were eligible for randomization (LT-Gem: three patients, LT alone: three patients). Two out of three patients discontinued adjuvant chemotherapy after LT due to intolerance. The study was prematurely terminated due to slow enrollment. One patient with PHC had underlying primary sclerosing cholangitis (PSC). Tumor-free margins could be achieved in all patients. In both the LT-Gem and the LT alone group, the cumulative 1-, 3-, and 5-year OS and DFS rates were 100%, 100%, 67%, and 100%, 67% and 67%, respectively. This prospective, multi-center study was prematurely terminated due to slow enrollment and a statement on the defined endpoints cannot be made. Nevertheless, long-term survival data are consistent with available retrospective data and confirm defined criteria for LT. Since more evidence of LT per se in unresectable PHC is urgently needed, a prospective, non-randomized follow-up study (pro-duct002) has since been launched.


Chronic exposure to benzene results in a unique form of dysplasia.
Hematotoxicity following chronic benzene exposure has been recognized for over a century, although the mechanism remains unknown. We describe a novel form of bone marrow dysplasia in 23 workers exposed to high concentrations of benzene. Distinguishing features of benzene-induced dysplasia include: marked dyserythropoiesis, eosinophilic dysplasia and abnormal cytoplasmic granulation of neutrophilic precursors. Hematophagocytosis, stromal degeneration and bone marrow hypoplasia are also seen. Severe bone marrow dysplasia is frequently accompanied by clonal T cell expansion and alterations in T lymphocyte subsets. No clonal cytogenetic abnormalities were observed. These results suggest that autoimmune-mediated bone marrow injury is an early or predisposing event in the pathogenesis of benzene-induced persistent hematopoietic disease.


[Comparison of the "Trigger" tool with the minimum basic data set for detecting adverse events in general surgery].
Surgery is a high risk for the occurrence of adverse events (AE). The main objective of this study is to compare the effectiveness of the Trigger tool with the Hospital National Health System registration of Discharges, the minimum basic data set (MBDS), in detecting adverse events in patients admitted to General Surgery and undergoing surgery. Observational and descriptive retrospective study of patients admitted to general surgery of a tertiary hospital, and undergoing surgery in 2012. The identification of adverse events was made by reviewing the medical records, using an adaptation of "Global Trigger Tool" methodology, as well as the (MBDS) registered on the same patients. Once the AE were identified, they were classified according to damage and to the extent to which these could have been avoided. The area under the curve (ROC) were used to determine the discriminatory power of the tools. The Hanley and Mcneil test was used to compare both tools. AE prevalence was 36.8%. The TT detected 89.9% of all AE, while the MBDS detected 28.48%. The TT provides more information on the nature and characteristics of the AE. The area under the curve was 0.89 for the TT and 0.66 for the MBDS. These differences were statistically significant (P<.001). The Trigger tool detects three times more adverse events than the MBDS registry. The prevalence of adverse events in General Surgery is higher than that estimated in other studies.


Efficient and simple genetic engineering of enteroids using mouse isolated crypts for investigating intestinal functions.
Intestinal epithelial cells separate subepithelial tissues from luminal environment formed with food, incoming pathogens, and resident intestinal microbiota, etc., and elicit various intestinal function. Enteroid, a three-dimensional culture system of small intestinal epithelial cells, has been widely used for analyzing the intestinal function, further a transgenic enteroid was developed to investigate the molecular mechanisms. However, conventional transgenic enteroid production method, which transfer gene into single stem cells, has limitations including low efficiency and time-consuming. Here we show that by gene transfer into small intestinal isolated crypts maintaining stem cell niche, a transgenic enteroid was obtained quickly and efficiently. Isolated crypts were transfected by lentiviral vector without separating into single cells, and transgenic enteroid composed of all lineages of intestinal epithelial cells was generated at day 7 with yield of 56%, maintaining the intestinal function in drug transport and innate immunity. Our efficient and simple transgenic enteroid generation method enables high-throughput investigation of intestinal epithelial cells and contributes to understanding intestinal function.


Genetic diversity and silencing suppression effects of Rice yellow mottle virus and the P1 protein.
PTGS (post-transcriptional gene silencing) is used to counter pathogenic invasions, particularly viruses. In return, many plant viruses produce proteins which suppress silencing directed against their RNA. The diversity of silencing suppression at the species level in natural hosts is unknown. We investigated the functional diversity of silencing suppression among isolates of the African RYMV (Rice yellow mottle virus) in rice. The RYMV-P1 protein is responsible for cell-to-cell movement and is a silencing suppressor. Transgenic gus-silencing rice lines were used to investigate intra-specific and serogroup silencing suppression diversity at two different levels: that of the virion and the P1 silencing suppressor protein. Our data provide evidence that silencing suppression is a universal phenomenon for RYMV species. However, we found considerable diversity in their ability to suppress silencing which was not linked to RYMV phylogeny, or pathogenicity. At the level of the silencing suppressor P1 alone, we found similar results to those previously found at the virion level. In addition, we showed that cell-to-cell movement of P1 was crucial for the efficiency of silencing suppression. Mutagenesis of P1 demonstrated a strong link between some amino acids and silencing suppression features with, one on the hand, the conserved amino acids C95 and C64 involved in cell-to-cell movement and the strength of suppression, respectively, and on the other hand, the non conserved F88 was involved in the strength of silencing suppression. We demonstrated that intra-species diversity of silencing suppression is highly variable and by mutagenesis of P1 we established the first link between silencing suppression and genetic diversity. These results are potentially important for understanding virus-host interactions.


RubisCO Early Oxygenase Activity: A Kinetic and Evolutionary Perspective.
RubisCO (D-ribulose 1,5-bisphosphate carboxylase/oxygenase) is Earth's main enzyme responsible for CO2 fixation via carboxylation of ribulose-1,5-bisphosphate (RuBP) into organic matter. Besides the carboxylation reaction, RubisCO also catalyzes the oxygenation of RuBP by O2 , which is probably as old as its carboxylation properties. Based on molecular phylogeny, the occurrence of the reactive oxygen species (ROS)-removing system and kinetic properties of different RubisCO forms, we postulated that RubisCO oxygenase activity appeared in local microoxic areas, yet before the appearance of oxygenic photosynthesis. Here, in reviewing the literature, we present a novel hypothesis: the RubisCO early oxygenase activity hypothesis. This hypothesis may be compared with the exaptation hypothesis, according to which latent RubisCO oxygenase properties emerged later during the oxygenation of the Earth's atmosphere. The reconstruction of ancestral RubisCO forms using ancestral sequence reconstruction (ASR) techniques, as a promising way for testing of RubisCO early oxygenase activity hypothesis, is presented.


Dichotic listening in 126 left-handed children: ear advantages, familial sinistrality and sex differences.
In the present study we report data on dichotic listening (DL) performance in 126 left-handed children. Four specific questions were addressed: (1) What is the percentage of left-handers in a large sample of children in Sweden? (2) What is the distribution of children showing a right ear (REA), left ear (LEA), and no ear (NEA) advantage in DL? (3) What is the relationship between ear advantage and familial sinistrality in children? (4) Are there sex differences among left-handed children, and if so, are these differences also reflected in DL performance? The results showed that the left-handers constituted 8.1% of the total sample of the screened subjects. The DL results showed 65.0% REA, 25.4% LEA, and 9.6% NEA. Of the subjects, 45.2% had left-handed relatives. Overall, there were more boys than girls in the sample (65.1% vs 34.9%). It is concluded that the present data match the sodium-Amytal data on left-handed adults with about 2/3 of a left-handed population with left hemisphere language dominance.


Screening of behaviorally active compounds based on the interaction between two chemosensory proteins and mung bean volatiles in Callosobruchus chinensis.
Chemosensory proteins (CSPs) are involved in the earliest steps of the olfactory process by binding and transporting odorants and play a crucial role in the insect's search for food and egg-laying sites. In the present study, the tissue expression profiles showed that both CchiCSP3 and CchiCSP5 of Callosobruchus chinensis were highly expressed in the adult antennae. Subsequently, the recombinant CchiCSP3 and CchiCSP5 proteins were analysed using fluorescence competitive binding assays, and both showed binding affinities for the three mung bean volatiles. Molecular docking and site-directed mutagenesis revealed four key amino acid residues in CchiCSP3 (L47, W80, Y81, and L84) and CchiCSP5 (Y28, K46, L49, and I72). Electroantennogram (EAG) and dual-choice biobehavioral assays showed that the antennae of adult C. chinensis were electrophysiologically active in response to stimulation with all three behaviorally active compounds and that octyl 4-methoxycinnamate and β-ionone had a significant luring effect on adult C. chinensis, whereas vanillin had a significant avoidance effect. Our study screened three effective behaviorally active compounds based on the involvement of two CchiCSPs in the recognition of mung bean volatiles, providing an opportunity to develop an alternative control strategy using behavioral disruptors to limit the impact of pests.


Method for the simultaneous determination of retinol and beta-carotene concentrations in human tissues and plasma.
To understand differential tissue distribution of retinoids and carotenoids, as it might influence biological processes in humans, we developed and demonstrated a method for measuring them in selected human tissues. The method includes internal standards and a secondary reference standard to eliminate the need for external standard calibration and to minimize sample-handling errors. Tissues were digested (saponified) in ethanolic KOH. Retinol and beta-carotene were extracted with organic solvent containing internal standards. Analytes were separated using isocratic liquid chromatography and quantified at 325 nm for retinol and 450 nm for beta-carotene. Plasma was analyzed in a similar way but without saponification. Retinal-O-ethyloxime and beta-apo-12'-carotenal-O-t-butyloxime served as internal standards. Plasma, breast, and fat from breast surgery patients and colon, liver, muscle, and fat from colon surgery patients were analyzed. Within-day relative standard deviations (RSDs) for plasma were <0.04 for beta-carotene and <0.03 for retinol, between-day RSDs were <0.05 for beta-carotene and <0.04 for retinol. Saponification ensured complete extraction of retinol and beta-carotene and removal of triglycerides that "foul" chromatographic columns. It seems retinol and beta-carotene concentrations in tissues and blood of cancer patients are the same or higher than those in corresponding tissues of patients without these cancers.


Structural basis for respiratory syncytial virus and human metapneumovirus neutralization.
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) continue to be a global burden to infants, the elderly, and immunocompromised individuals. In the past ten years, there has been substantial progress in the development of new vaccine candidates and therapies against these viruses. These advancements were guided by the structural elucidation of the major surface glycoproteins for these viruses, the fusion (F) protein and attachment (G) protein. The identification of immunodominant epitopes on the RSV F and hMPV F proteins has expanded current knowledge on antibody-mediated immune responses, which has led to new approaches for vaccine and therapeutic development through the stabilization of pre-fusion constructs of the F protein and pre-fusion-specific monoclonal antibodies with high potency and efficacy. In this review, we describe structural characteristics of known antigenic sites on the RSV and hMPV proteins, their influence on the immune response, and current progress in vaccine and therapeutic development.


Advocating for Breast Heath Education for College-Age Students.
Awareness of the risk factors associated with breast cancer can alleviate fear and anxiety, and can lead people to pursue prevention. This article describes a university's annual breast health education event focused on breast health awareness and breast cancer education. Community health organizations and student organizations serve as exhibitors and provide students with opportunities to test their knowledge and dispel myths. Over the past 5 years this event has reached more than 2,000 students. Initiatives such as this event provide health educators with an opportunity to reach this highly vulnerable population.


Synthesis of Organometallic Oligonucleotides through Oximation with Metalated Benzaldehydes.
A phthaloyl-protected aminooxymethyl-C-2'-deoxyriboside building block has been prepared and incorporated in the middle of an oligodeoxyribonucleotide. Removal of the phthaloyl protection followed by on-support oximation with either mercurated or palladated benzaldehydes yielded oligonucleotides bearing the respective benzaldoxime metallacycles.


The acquired immune deficiency syndrome: problems associated with the management of Pneumocystis carinii pneumonia.
Four fatal and two non-fatal cases of pneumonia caused by Pneumocystis carinii and one case of co-trimoxazole-responsive interstitial pneumonia, all in homosexual patients with the acquired immune deficiency syndrome, are described. The lack of clinical signs in the chest and of abnormal radiological findings at presentation in three of the six patients with P. carinii infection, the rapidly progressive course of the disease, as well as the need for early diagnosis and treatment are stressed. The possibility of chemoprophylaxis against P. carinii is discussed.


A hospital at home case report: Prolonged amphotericin B therapy via elastomeric pump.
Hospital at home is an alternative means of providing inpatient care for a patient requiring prolonged liposomal amphotericin B therapy. Hospital at home is a unique care model that allows patients to receive inpatient hospital care within the comfort of their home and can be seen as an alternative care site for patients with complex treatment regimens that may require prolonged hospitalization. Hospital systems have increasingly begun incorporating hospital at home programs into their inpatient service lines. We present the case of a patient with disseminated histoplasmosis requiring a prolonged course of intravenous liposomal amphotericin B therapy. Because of the complex administration and stability of this medication, care is often provided in an inpatient setting. The Vanderbilt University Medical Center Hospital at Home team was able to coordinate resources and services to allow for this patient to receive acute hospital care at home and continue to receive amphotericin B infusion. This experience spotlights how hospital at home can be considered for patients requiring ongoing inpatient care for prolonged intravenous treatment courses.


Mono and two-dimensional 500-MHz characterization of synthetic bombesin and related peptides in DMSO and DMSO-water.
The proton nmr characterization of bombesin (BBS) and of two peptide fragments corresponding to the (1-6) and (6-14) sequences has been carried out at 500 MHz in dimethyl sulfoxide (DMSO-d6) using two-dimensional (2D) homo and 1H-13C heterocorrelated techniques. All resonances in the nmr spectra have been assigned and several coupling constants have been measured. The backbone J alpha CH-NH coupling constants are quite similar and around 7.8-8.2 Hz, pointing to an unfolded structure in DMSO-d6. The possibility of secondary structures in highly viscous mixtures of DMSO-d6-water was investigated. The existence of sequential nuclear Overhauser enhancement (NOE) effects in the C-terminal nonapeptide section may indicate a preferential site for secondary structuring.


New record of a Mesozoic gondwanatherian mammaliaform from Southern Patagonia.
Gondwanatheria is an enigmatic mammaliaform clade distributed in the Cretaceous and Paleogene of South America, Africa, Madagascar, India and Antarctica. The Mesozoic record in South America is restricted to the Latest Cretaceous of Río Negro and Chubut provinces, Argentina and Magallanes Region of southern Chile. The aim of the present contribution is to describe a new specimen of gondwanatherian mammaliaforms from beds belonging to the Maastrichtian Chorrillo Formation, cropping out 30 km SW of El Calafate, Santa Cruz Province, Argentina. It is represented by a single molariform referable to the species Magallanodon baikashkenke with which it shares a unique combination of characters. Analysis of the unique combination of characters exhibited by Magallanodon shed doubts on the monophyly of Ferugliotheriidae and suggest that South American taxa may be closely related to each other. The wide geographical distribution and occurrence of gondwanatherians on geological units of diverse origins suggest that they were capable of facing disparate environmental conditions.


Accumulation and distribution of organochlorines (PCBs and DDTs) in various organs of Stenella coeruleoalba and a Tursiops truncatus from Mediterranean littoral environment (France).
The objective of the present study is to determine the levels of contamination by PCBs, DDT and its metabolites in dolphins failed on the coasts of the Mediterranean sea. Samples are represented by six Stenella coeruleoalba and a Tursiops truncatus collected in 2000 and 2003. The studies are achieved on the blubber, the heart, the liver, the kidney, the muscle and the lung. The concentrations of PCBs and DDT are very high in all tissues and organs analyzed. For the PCBs, the concentrations vary between 43,838 and 110,343 microg/kg lipid basis in the blubber, 601 and 39444 microg/kg dried weight in the liver, 1375 and 34512 microg/kg dried weight in the muscle, 3151 and 17082 microg/kg dried weight in the heart, 674 and 12365 microg/kg dried weight in the kidney and finally between 648 and 4118 microg/kg dried weight in the lung. These values are comparable to those previously obtained in our laboratory and by other authors during the years 1990 on the Mediterranean environment. Significant differences in concentrations are noted in tissues and organs, neither according to the age, nor according to the gender. In all the analyzed samples, the contents in PCBs are higher than those of DDT. The average ratios of pp'-DDE/SigmaDDT are close to 0.6 which shows the metabolization of these compounds along the years. The examination of the profiles of congeners shows that the hexachlorinated molecules are dominating in all tissues and organs which supposes the different animals were especially exposed to Pyralen-type compounds of transformer (Dp6).


[Potentialities of a fluorescent method in determining the completeness of resection of the stomach in cancer].
Examined were 78 resected stomachs of the patients, operated on for infiltrative cancer. Before the operation, a fluorescent dye was injected to all the patients. Fluorescence was excited by light with a wavelength of 441 nm, and fixed at the wavelength of the dye fluorescence of 520 nm. In histologic study of the brightly fluorescing sites, it was established that in 3 cases, the resection was performed through the tumour, and in 4--a tumour was invading along the tela submucosa and muscular layer up to the margin of resection.


Asymmetric Brønsted Acid Catalyzed Substitution of Diaryl Methanols with Thiols and Alcohols for the Synthesis of Chiral Thioethers and Ethers.
An enantioselective addition of thiols and alcohols to aza-ortho-quinone methides, starting from diaryl methanols, was developed. The asymmetric additions occur under mild reaction conditions in the presence of chiral phosphoric acids and furnish the corresponding adducts with excellent yields and enantioselectivities.


Half sphere and single clip-bar retained implant supported silicone auricular prosthesis.
Implant supported auricular prosthesis can be retained by several mechanical means, one of them being the Hader bar and clip system. Conventionally two or more rider clips are used. This technique describes a modified Hader bar design to maintain retention while eliminating the requirement of a second clip, significantly bringing down cost.


Effectiveness of Poster and/or Mini-Lecture on Genetic Disorders and Birth Defects Related Knowledge among Secondary Level Students of Kaski, Nepal.
Almost seven percent of disease burden is due to genetic disorders and birth defects and they are associated to genetic as well as environmental factors. Prevention of such problems by making aware and increasing knowledge level with the help of health education during adolescence is cost-effective among others. In this context, current study proposed whether mini-lecture and/or poster is/are effective in changing adolescents' knowledge regarding genetic disorders and birth defects. Mini-lectures followed by posters on genetic disorders and birth defects were used for intervention group, whereas for control, only mini-lectures based on health promotion were delivered by trained personnel in nine through 12 grade students of conveniently selected two public schools of Kaski district using quasi-experimental design. Knowledge was assessed using a pretested inventory at baseline, after two weeks of mini-lectures and two more weeks after poster for intervention group, whereas, only at baseline and two weeks after mini-lectures for control. Statistical analysis was carried out to compare the intervention group of 133 students with that of control group of 154. Mean knowledge increments among control and intervention groups were 0.20 and 0.68 points respectively after mini-lecture. An addition of 0.84 points gained after the poster, yielding overall increment of 1.52 in intervention group. Inferential analysis showed that effect of control was not effective (p=0.60), whereas mini-lecture (p=0.032), poster (p=0.008) and both mini-lecture and poster (p<0.001) were effective. The mini-lecture and/or poster for grade nine through 12 are effective methods and media for bringing about changes in knowledge of adolescents regarding genetic disorders and birth defects.


Middle Meningeal Artery Aneurysm in a Giant Meningioma.
Nontraumatic perilesional aneurysms are thought to occur because of high-flow demands of feeding arteries and neoangiogenesis of hypervascular lesions, most commonly in vascular malformations, but they can rarely be associated with tumors as well. Most of these perilesional aneurysms are from intracranial vasculature associated with branches off the internal carotid artery. We report the unique case of a middle meningeal artery aneurysm associated with a giant convexity meningioma seen on a preoperative angiogram.


Individual and community level associates of contraceptive use in Ethiopia: a multilevel mixed effects analysis.
Family planning is one of the four pillars of safe motherhood initiative to reduce maternal death in developing countries. Despite progress in contraceptive use, unmet needs are wide open and fertility remains high. Ethiopia have a higher fertility rate which contributes to maternal and child health destitution, putting pressure on the already weak health system. This study examined individual and community-level factors associated with contraceptive use in Ethiopia. Data from Ethiopian Demographic and Health Survey 2016 were used to identify individual and community level associated factors among reproductive-age women. Non-pregnant, fecund and sexually active women aged 15-49 were included. Six hundred forty-two communities and 6854 women were involved from this two-stage cluster sampled data. The analysis was done using two-level mixed-effects logistic regression to determine fixed effects of individual and community-level factors and random intercept of between characteristics. From the total eligible women for contraceptive use 2393 (34.9%) of them were users. Injectables were the commonest of all contraceptive methods. Various individual-level variables were associated with contraceptive use. Household wealth index, women's age, number of living children, husband's occupation, ever experience of a terminated pregnancy, current working status of the women, number of births in the last 3 years, and hearing of FP messages through different media were significantly associated individual-level variables after adjusting other factors. Community characteristics like region, place of residence, religion, and community-level wealth were the factors associated with contraceptive use. Both individual and community-level characteristics were significant predictors of use of contraceptives in Ethiopian women. Besides the individual-level factors, interventions should also consider community-level associates.


Head and whole-body jerking in guinea pigs are differentially modulated by 5-HT1A, 5-HT1B/1D and 5-HT2A receptor antagonists.
The present study examined the role of 5-hydroxytryptamine 5-HT receptor subtypes on 5-hydroxytryptamine- (5-HT-) mediated myoclonus in guinea pigs, evaluating head and whole-body jerking as two distinct behavioural responses. Myoclonus was induced by the 5-HT precursor L-5-hydroxytryptophan (L-5-HTP) and the non-selective 5-HT1A/1B/5-HT2 receptor agonist 5-methoxy-N,N-dimethyl-tryptamine (5-MeODMT). The selective 5-HT1A receptor antagonist WAY100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cycloh exanecarboxamide trihydrochloride) inhibited both head and whole-body jerking. The selective 5-HT1B/1D receptor antagonist GR127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1 ,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-carboxamide hemifumarate) only inhibited whole-body jerking, which resulted in unmasked head jerking. Co-administration of GR127935 and the selective 5-HT2A receptor antagonist MDL100.151 ((+/-)-alpha-(2,3-dimethoxyphenyl)-1-[-2-(4-fluorphenyl)ethyl]-4-+ ++piperidinmethanol) caused a complete inhibition of whole-body as well as head jerking. MDL100.151 had only limited effect on myoclonic jerking when given alone. The inhibitory effects of the 5-HT receptor antagonists on either L-5-HTP- or 5-MeODMT-induced myoclonus were found to be very similar. These data confirm a role for the 5-HT1A and 5-HT1B/1D receptors and suggest a role for 5-HT2A receptors in mediating myoclonus in guinea pigs. Moreover, the study shows that by considering head and whole-body jerking as two pharmacologically distinct behavioural responses, subtype specific 5-HT1A, 5-HT1B/1D and 5-HT2A receptor antagonists can be distinguished.


Interferometric scattering microscopy and its combination with single-molecule fluorescence imaging.
Interferometric scattering microscopy (iSCAT) is a light scattering-based imaging modality that offers a unique combination of imaging speed and precision for tracking nanoscopic labels and enables label-free optical sensing down to the single-molecule level. In contrast to fluorescence, iSCAT does not suffer from limitations associated with dye photochemistry and photophysics, or the requirement for fluorescent labeling. Here we present a protocol for constructing an iSCAT microscope from commercially available optical components and demonstrate its compatibility with simultaneously operating single-molecule, objective-type, total internal reflection fluorescence microscopy. Given an intermediate level of experience with optics and microscopy, for instance graduate-level familiarity with laser beam steering and optical components, this protocol can be completed in a time frame of 2 weeks.


Program to estimate parameters of linear systems without numerical differentiation.
This paper describes a computer program for estimating the parameters of a linear differential equation systen with constant coefficients by use of a nonlinear least-squares method. For minimization the sum of squares of an existing standard program, the Gauss-Newton gradient procedure, is employed. The differential equation system is solved by the Taylor expansion method. The advantage of this approach is that the derivatives with respect to the parameters are available without numerical differentiation. Therefore the inaccuracy inherent in numerical differentiation and the problem of choosing the modification of the parameters are eliminated. The given procedure is applicable for all the first order gradient methods. The presented method was tested with generated data from a four-compartmental model.


Neurocognitive predictors of food memory in healthy adults - A preregistered analysis.
Memory processes have long been known to determine food choices (Rozin & Zellner, 1985) but recognition memory of food and its cognitive, homeostatic and neuroanatomical predictors are still largely understudied. 60 healthy, overweight, non-restrictive eating adults (20 females) took part in a food wanting and subsequent food recognition and lure discrimination task at four time points after a standardized breakfast shake. With advanced tractography of 3 T diffusion-weighted imaging data, we investigated the influence of the uncinate fasciculus' (UF) brain microstructure on the interplay of food wanting and memory processes. The analysis was preregistered in detail and conducted with Bayesian multilevel regression modeling. Target recognition (d') and lure discrimination (LDI) performance of food tended to be higher than of art images while single image food memory accuracy evidently dominated art memory. On this single item level, wanting enhanced recognition accuracy and caloric content enhanced food memory accuracy. The enhancement by reward anticipation was most pronounced during memory encoding. Subjective hunger level did not predict performance on the memory task. The microstructure of the UF did neither evidently affect memory performance outcomes nor moderate the wanting enhancement of the recognition accuracy. Interestingly, female participants outperformed males on the memory task, and individuals with stronger neuroticism showed poorer memory performance. We shed light on to date understudied processes in food decision-making: reward anticipation influenced recognition accuracy and food memory was enhanced by higher caloric content, both effects might shape food decisions. Our findings indicate that brain microstructure does not affect food decision processes in adult populations with overweight. We suggest extending investigation of this interplay to brain activity as well as to populations with eating behaviour disorders.


Combined exercise training improved exercise capacity and lung inflammation in rats with hepatopulmonary syndrome.
Physical exercise training attenuates pulmonary inflammation, but its effects on impaired respiratory function caused by hepatopulmonary syndrome (HPS) have not been evaluated. We determined if the combination of moderate intensity aerobic and resistance training during HPS development modifies exercise capacity, respiratory system mechanics, and lung inflammation responses. Wistar rats were randomly divided into sham, HPS, and HPS + combined exercise training groups. Fifteen days after HPS induction, a moderate intensity aerobic plus resistance exercise training protocol was performed five times a week for 5 weeks on alternate days. Exercise capacity, respiratory system mechanics, lung inflammation, pulmonary morphology, and immunohistochemistry were evaluated. Overall, our findings indicated that combined exercise training efficiently increased the maximal running and resistance capacity of HPS animals. The training regimen reduced the expression of P2X7 in parenchymal leukocytes (P < 0.01), partially restored the expression of interleukin-10 in airway epithelium (P < 0.01), and increased the expression of TFPI in the airway epithelium (P < 0.01) as well as reduced its expression in parenchymal leukocytes (P < 0.01). However, exercise training did not attenuate HPS-induced respiratory mechanical derangements or lung tissue remodeling. Combined exercise training can elicit adaptation with regard to both maximal running capacity and maximum strength and modify the expression of P2X7 and TFPI in parenchymal leukocytes and that of IL-10 in airway epithelium.


Altitudinal variation in stomatal conductance, nitrogen content and leaf anatomy in different plant life forms in New Zealand.
This study is part of a series of investigations on the influence of altitude on structure and function of plant leaves. Unlike most other mountain areas, the Southern Alps of New Zealand provide localities where physiologically effective moisture stress occurs neither at high nor at low elevation, but the changes in temperature and radiation with elevation are similar or even steeper than in most other regions. In comparison with results from other mountains, where moisture may impair plant functioning at low elevation, this study allows an estimation of the relative role of water for the expression of various leaf features typically associated with alpine plants. Maximum leaf diffusive conductance (g), leaf nitrogen content (LN), stomatal density (n) and distribution, as well as area (A), thickness (d) and specific area (SLA) of leaves were studied. Three different plant life forms were investigated over their full altitudinal range (m): trees, represented by Nothofagus menziesii (1,200 m), ericaceous dwarf shrubs (1,700 m), and herbaceous plants of the genus Ranunculus (2,500 m). In all three life forms g, LN, and n increased, while SLA and A decreased with elevation. Recent investigations have found similar trends in other mountains from the temperate zone, but the changes are larger in New Zealand than elsewhere. Herbs show the greatest differences, followed by shrubs and then trees.It is concluded that g is dependent upon light climate rather than water supply, whereas SLA and related structural features appear to be controlled by the temperature regime, as they show similar altitudinal changes under different light and moisture gradients. The higher leaf nitrogen content found at high elevations in all three life forms, suggests that metabolic activity of mature leaves is not restricted by low nitrogen supply at high altitude. In general, the leaves of herbaceous plants show more pronounced structural and functional changes with altitude than the leaves of shrubs and trees.


Association Between Clozapine Plasma Concentrations and Treatment Response: A Systematic Review, Meta-analysis and Individual Participant Data Meta-analysis.
Although therapeutic drug monitoring of clozapine is recommended, its optimisation is often adjusted only on the basis of dosage. The aim of this study was to assess the link between clozapine plasma concentrations and clinical response by a meta-analysis of published studies and by an individual participant data meta-analysis. We conducted a computerised search of bibliographic databases (EMBASE, PubMed, Clinical Trials, and Web of Science) to identify studies that assessed the relationship between clozapine serum or plasma concentrations and clinical efficacy. Using pooled data, we investigated the association between improvement of clinical outcome and clozapine or norclozapine plasma concentrations, the sum of clozapine and norclozapine plasma concentrations, and the coefficient of variation of clozapine plasma concentrations. Using available individual data, we assessed the relationship between clozapine plasma concentrations and clinical response (changes in the Brief Psychiatric Rating Scale score) and identified a threshold level for a favourable clinical response. Fifteen studies satisfied inclusion criteria. Our meta-analysis showed that responders had clozapine plasma concentrations that were, on average, 117 ng/mL higher than non-responders. The patients with plasma clozapine concentrations above the thresholds identified in each study had a higher likelihood of responding (odds ratio = 2.94, p < 0.001). Norclozapine plasma concentrations were not associated with a clinical response. The meta-analysis of individual data supported this result and confirmed the link between clozapine concentrations and a change in the Brief Psychiatric Rating Scale score and/or the probability of clinical response. Finally, with the analysis of the coefficient of variation of clozapine plasma concentrations, we found that a greater inter-individual fluctuation in plasma concentrations was associated with a loss of clinical response. Our work confirmed that, in contrast to clozapine doses, clozapine plasma concentrations were related to a favourable clinical response, with a mean difference between responders and non-responders of 117 ng/mL. A threshold for a treatment response of 407 ng/mL was determined, with a high discriminatory capacity, and a sensitivity and specificity of 71% and 89.1%, respectively.


Comparison of artificial intelligence algorithms and their ranking for the prediction of genetic merit in sheep.
As the amount of data on farms grows, it is important to evaluate the potential of artificial intelligence for making farming predictions. Considering all this, this study was undertaken to evaluate various machine learning (ML) algorithms using 52-year data for sheep. Data preparation was done before analysis. Breeding values were estimated using Best Linear Unbiased Prediction. 12 ML algorithms were evaluated for their ability to predict the breeding values. The variance inflation factor for all features selected through principal component analysis (PCA) was 1. The correlation coefficients between true and predicted values for artificial neural networks, Bayesian ridge regression, classification and regression trees, gradient boosting algorithm, K nearest neighbours, multivariate adaptive regression splines (MARS) algorithm, polynomial regression, principal component regression (PCR), random forests, support vector machines, XGBoost algorithm were 0.852, 0.742, 0.869, 0.915, 0.781, 0.746, 0.742, 0.746, 0.917, 0.777, 0.915 respectively for breeding value prediction. Random forests had the highest correlation coefficients. Among the prediction equations generated using OLS, the highest coefficient of determination was 0.569. A total of 12 machine learning models were developed from the prediction of breeding values in sheep in the present study. It may be said that machine learning techniques can perform predictions with reasonable accuracies and can thus be viable alternatives to conventional strategies for breeding value prediction.


Sonographic demonstration of portal venous gas in necrotizing enterocolitis.
Portal vein gas embolism was demonstrated by ultrasound in a preterm infant with necrotizing enterocolitis. This sign could not be detected radiographically. It is speculated that portal venous gas occurs more frequently than hitherto inferred from radiological studies. This observation points to the value of ultrasonography in providing early objective evidence in support of the diagnosis of NEC. The favourable outcome for the patient proves that portal venous gas embolism is not necessarily associated with a fulminant course of enterocolitis.


Subcellular distribution of hypothalamic prolactin-like immunoreactivity.
Prompted by interest in immunohistochemical reports of prolactin-like immunoreactivity (PLI) in the rat hypothalamus, we investigated and have reported that an immunoreactive and bioactive prolactin-like material can be extracted from the rat hypothalamus. In the present communication the subcellular distribution of this protein is reported. Using a sensitive and specific radioimmunoassay for rat prolactin and a standardized procedure for subcellular fractionation of neuronal tissue, we have found that 90% of hypothalamic PLI is particulate-bound with only 10% remaining in the S4 or cytosolic fraction. Almost 80% of the particulate-bound PLI is found in the P2 fraction containing myelin, synaptosomes and mitochondria. When P2 is further fractioned on a discontinuous sucrose density gradient, approximately 66% of the P2-associated PLI was found in subfractions rich in synaptosomes and poor in myelin and mitochondria. Such findings support the probability that hypothalamic PLI functions trans-synaptically as a neuromodulator in the brain.


Individual and joint toxicity effects of Cu, Cr(III), and Cr(VI) on pakchoi: a comparison between solution and soil cultures.
The single and joint toxicity effects of Cu, Cr(III), and Cr(VI) on the root elongation of pakchoi in solution and soil were investigated. The median effective concentration (EC(50)) was determined to examine the toxic thresholds of the test elements. The results showed that individual contamination by Cu, Cr(III), or Cr(VI) can inhibit the root elongation of pakchoi. The EC(50) values of the test elements were 2.02 mg/L and 195.8 mg/kg, 62.2 mg/L and 1,773 mg/kg, and 6.88 mg/L and 8.08 mg/kg in solution and soil, respectively. Toxic unit (TU) was introduced to determine the outcome in combined tests, and different behaviors were observed in both solution and soil. The coexistence of Cu and Cr(III) in solution exhibited an antagonistic effect (EC(50mix) = 1.76 TU(mix)), whereas a synergistic effect was observed in soil (EC(50mix) = 0.76 TU(mix)). In contrast, combined Cu-Cr(VI) showed a less than additive toxicity both in solution and soil, with EC(50mix) values of 3.31 and 1.24 TU(mix). In conclusion, the coexistence of toxicity in Cu-Cr(III) and Cu-Cr(VI) differs from the toxicity exhibited individually by Cu, Cr(III), and Cr(VI). Heavy metal interaction also changes depending on the medium.


Does China's increasing coupling of 'urban population' and 'urban area' growth indicators reflect a growing social and economic sustainability?
Over the last four decades, China has experienced rapid parallel economic development and urbanization, leading to internal mass -migrations of its people from increasingly marginalized rural areas to urban centers where job opportunities and wealth are now concentrated. We compare the relative temporal growth trends in population-related and land-(i.e., area-) related urbanization systems to evaluate China's urbanization in the context of the 'New-Type' Urbanization Program (2014-2020). Based on coupling coordination models, we observed that the two systems were overall slightly decoupled since spatial urban expansion commonly outgrew urban population growth, but the degree of coordination between the two parameters was increasing. Employing exploratory spatial data analysis, we revealed that a high degree of coupling coordination has spread from Eastern to Western provinces. Urban planning and land policies have contributed to an increasing urban vegetation cover and the control of excessive urban land expansions. While China's urbanization appears to have become increasingly sustainable due to the increasing degree of coupling coordination between its subsystems, ongoing urban expansions require strong oversight to limit the environmental impacts of the country's sprawling mega-cities.


Sources of Vibrio mimicus contamination of turtle eggs.
Vibrio mimicus contamination of sand increased significantly during the arrival of the olive ridley sea turtles (Lepidochelys olivacea) at Ostional anidation beach, Costa Rica. Statistical analysis supports that eggs are contaminated with V. mimicus by contact with the sand nest. V. mimicus was isolated from eggs of all nests tested, and ctxA+ strains were found in 31% of the nests, all of which were near the estuary.


[Association between the characteristics of the neighborhood environment and physical activity].
To assess the relationship between the physical and social attributes of the neighborhood environment and levels of total physical activity (PA), leisure time PA, and active commuting PA in adults. The present cross-sectional study comprised 1500 adults (51.1% women) aged 15-74 years from the Autonomous Region of Madrid (Spain). Data were collected through a structured telephone interview. PA was assessed using the Global Physical Activity Questionnaire, version 2. Neighborhood attributes were assessed with the Environmental Module of the International Physical Activity Prevalence Study. The factors associated with a higher probability of achieving moderate to high levels of total PA and active commuting PA were living in high density residential areas, the presence of shops close to the residential area, public transport stops 10-15 minutes away from the home, and the existence of sidewalks in most of the neighborhood's streets (all p <0,05). The factors associated with moderate to high leisure time PA levels were the presence of active people in the residential area and the presence of low-cost recreational facilities (both p <0,05). Our findings suggest that most of the physical and social attributes of the neighborhood environment examined in this study are associated with total and active commuting PA, whereas only certain neighborhood attributes seem to be associated with leisure time PA.


Environmental-sanitary risk analysis procedure applied to artificial turf sports fields.
Owing to the extensive use of artificial turfs worldwide, over the past 10 years there has been much discussion about the possible health and environmental problems originating from styrene-butadiene recycled rubber. In this paper, the authors performed a Tier 2 environmental-sanitary risk analysis on five artificial turf sports fields located in the city of Turin (Italy) with the aid of RISC4 software. Two receptors (adult player and child player) and three routes of exposure (direct contact with crumb rubber, contact with rainwater soaking the rubber mat, inhalation of dusts and gases from the artificial turf fields) were considered in the conceptual model. For all the fields and for all the routes, the cumulative carcinogenic risk proved to be lower than 10(-6) and the cumulative non-carcinogenic risk lower than 1. The outdoor inhalation of dusts and gases was the main route of exposure for both carcinogenic and non-carcinogenic substances. The results given by the inhalation pathway were compared with those of a risk assessment carried out on citizens breathing gases and dusts from traffic emissions every day in Turin. For both classes of substances and for both receptors, the inhalation of atmospheric dusts and gases from vehicular traffic gave risk values of one order of magnitude higher than those due to playing soccer on an artificial field.


The development of quality indicators to improve psychosocial care in dementia.
The evidence for the effectiveness of psychosocial interventions in dementia care is growing but the implementation of available evidence is not automatic. Our objective was to develop valid quality indicators (QIs) for psychosocial dementia care that facilitate the implementation process in various countries and settings. A RAND-modified Delphi technique was used to develop a potential set of QIs. Two multidisciplinary, international expert panels were involved in achieving content and face validity. Consensus on the final set was reached after a conference meeting where a third panel of dementia experts discussed measurability and applicability of the potential set. A retrospective cohort study was conducted to study the feasibility of using the final set in day care centers, hospitals, and nursing homes in Spain and The Netherlands. A total of 104 recommendations were selected from guidelines and systematic reviews and appraised for their contribution to improving the quality of dementia care by 49 dementia experts. Twenty-five experts attended the conference meeting and reached consensus on a set of 12 QIs representing the key elements of effective psychosocial care, such as shared decision-making and interventions tailored to needs and preferences. Data from 153 patient records showed that all but one QI subitem were applicable to all three settings in both countries. Our multidisciplinary and multinational strategy resulted in a set of unique QIs that aims exclusively at assessing the quality of psychosocial dementia care. Following implementation, these QIs will assist dementia care professionals to individualize and tailor psychosocial interventions.


Accurate determination of node and arc multiplicities in de bruijn graphs using conditional random fields.
De Bruijn graphs are key data structures for the analysis of next-generation sequencing data. They efficiently represent the overlap between reads and hence, also the underlying genome sequence. However, sequencing errors and repeated subsequences render the identification of the true underlying sequence difficult. A key step in this process is the inference of the multiplicities of nodes and arcs in the graph. These multiplicities correspond to the number of times each k-mer (resp. k+1-mer) implied by a node (resp. arc) is present in the genomic sequence. Determining multiplicities thus reveals the repeat structure and presence of sequencing errors. Multiplicities of nodes/arcs in the de Bruijn graph are reflected in their coverage, however, coverage variability and coverage biases render their determination ambiguous. Current methods to determine node/arc multiplicities base their decisions solely on the information in nodes and arcs individually, under-utilising the information present in the sequencing data. To improve the accuracy with which node and arc multiplicities in a de Bruijn graph are inferred, we developed a conditional random field (CRF) model to efficiently combine the coverage information within each node/arc individually with the information of surrounding nodes and arcs. Multiplicities are thus collectively assigned in a more consistent manner. We demonstrate that the CRF model yields significant improvements in accuracy and a more robust expectation-maximisation parameter estimation. True k-mers can be distinguished from erroneous k-mers with a higher F1 score than existing methods. A C++11 implementation is available at https://github.com/biointec/detox under the GNU AGPL v3.0 license.


Comparative effectiveness and cost-effectiveness analysis of a urine metabolomics test vs. alternative colorectal cancer screening strategies.
Despite the success of provincial screening programs, colorectal cancer (CRC) is still the third most common cancer in Canada and the second most common cause of cancer-related death. Fecal-based tests, such as fecal occult blood test (FOBT) and fecal immunochemical test (FIT), form the foundation of the provincial CRC screening programs in Canada. However, those tests have low sensitivity for CRC precursors, adenomatous polyps and have low adherence. This study evaluated the effectiveness and cost-effectiveness of a new urine metabolomic-based test (UMT) that detects adenomatous polyps and CRC. A Markov model was designed using data from the literature and provincial healthcare databases for Canadian at average risk for CRC; calibration was performed against statistics data. Screening strategies included the following: FOBT every year, FIT every year, colonoscopy every 10 years, and UMT every year. The costs, quality adjusted life years (QALY) gained, and incremental cost-effectiveness ratios (ICERs) for each strategy were estimated and compared. Compared with no screening, a UMT strategy reduced CRC mortality by 49.9% and gained 0.15 life years per person at $42,325/life year gained in the base case analysis. FOBT reduced CRC mortality by 14.9% and gained 0.04 life years per person at $25,011/life year gained. FIT reduced CRC mortality by 35.8% and gained 0.11 life years per person at $25,500/life year while colonoscopy reduced CRC mortality by 24.7% and gained 0.08 life years per person at $50,875/life year. A UMT strategy might be a cost-effective strategy when used in programmatic CRC screening programs.


[The effect of mildronate and related substances on levels of thyroid hormones and some intermediates of lipid and carbohidrate metabolism in the hyperthyroid and hypothyroid rats].
We have investigated effects of Mildronate, gamma-butyrobetaine (GBB) and their combination ("Neomildronate") on the plasma levels of thyroid gland hormones and some intermediates of basal metabolism (free fatty acids, triglycerides, glucose) in rats with different dysfunctions of thyroid gland, including idiopathic hyperfunction and hypofunction induced by propylthiouracil or L-carnitin administration. Histological investigation of the thyroid gland was also performed. Intraperitoneal injections of Mildronate (150 mg/kg) during 20 days to Wistar male rats with elevated level of thyroid hormones and basal metabolism normalized thyroxine level and parameters of lipid metabolism. Mildronate, GBB and their combination did not affect the natural resurgence of rats with experimental hypofunction induced by propylthiouracil or L-carnitin administration. The possible biochemical role of given treatment in regulation of thyroid gland function is discussed.


Regulatory innate lymphoid cells suppress innate immunity and reduce renal ischemia/reperfusion injury.
Innate lymphoid cells are a recently recognized group of immune cells with critical roles in tissue homeostasis and inflammation. Regulatory innate lymphoid cells are a newly identified subset of innate lymphoid cells, which play a suppressive role in the innate immune response, favoring the resolution of intestinal inflammation. However, the expression and role of regulatory innate lymphoid cells in kidney has not been reported. Here, we show that regulatory innate lymphoid cells are present in both human and mouse kidney, express similar surface markers and form a similar proportion of total kidney innate lymphoid cells. Regulatory innate lymphoid cells from kidney were expanded in vitro with a combination of IL-2, IL-7 and transforming growth factor-β. These cells exhibited immunosuppressive effects on innate immune cells via secretion of IL-10 and transforming growth factor-β. Moreover, treatment with IL-2/IL-2 antibody complexes (IL-2C) promoted expansion of regulatory innate lymphoid cells in vivo, and prevent renal ischemia/reperfusion injury in Rag-/- mice that lack adaptive immune cells including Tregs. Depletion of regulatory innate lymphoid cells with anti-CD25 antibody abolished the beneficial effects of IL-2C in the Rag-/- mice. Adoptive transfer of ex vivo expanded regulatory innate lymphoid cells improved renal function and attenuated histologic damage when given before or after induction of ischemia/reperfusion injury in association with reduction of neutrophil infiltration and induction of reparative M2 macrophages in kidney. Thus, our study shows that regulatory innate lymphoid cells suppress innate renal inflammation and ischemia/reperfusion injury.


Targeted disruption of Col8a1 and Col8a2 genes in mice leads to anterior segment abnormalities in the eye.
Collagen VIII is localized in subendothelial and subepithelial extracellular matrices. It is a major component of Descemet's membrane, a thick basement membrane under the corneal endothelium, where it forms a hexagonal lattice structure; a similar structure, albeit less extensive, may be formed in other basement membranes. We have examined the function of collagen VIII in mice by targeted inactivation of the genes encoding the two polypeptide subunits, Col8a1 and Col8a2. Analysis of these mice reveals no major structural defects in most organs, but demonstrates that type VIII collagen is required for normal anterior eye development, particularly the formation of a corneal stroma with the appropriate number of fibroblastic cell layers and Descemet's membrane of appropriate thickness. Complete lack of type VIII collagen leads to dysgenesis of the anterior segment of the eye: a globoid, keratoglobus-like protrusion of the anterior chamber with a thin corneal stroma. Descemet's membrane is markedly thinned. The corneal endothelial cells are enlarged and reduced in number, and show a decreased ability to proliferate in response to different growth factors in vitro. An important function of collagen VIII may therefore be to generate a peri- or subcellular matrix environment that permits or stimulates cell proliferation.


Impact of anaerobiosis strategy and bioreactor geometry on the biochemical response of Clostridium butyricum VPI 1718 during 1,3-propanediol fermentation.
The impact of anaerobiosis strategy on 1,3-propanediol production during cultivation of Clostridium butyricum VPI 1718 in different size bioreactors was studied. In batch trials with N2 gas infusion, the fermentation was successfully accomplished, regardless of initial glycerol concentration imposed and bioreactor geometry. However, in the absence of N2 continual sparging, significant variations concerning the biochemical response of the strain were observed. Specifically, at 1-L bioreactor, the absence of N2 infusion at high initial glycerol concentration induced lactate dehydrogenase activity and thus lactic acid synthesis, probably due to partial blockage of phosphoroclastic reaction caused by insufficient self-generated anaerobiosis environment. During fed-batch cultivation with continual N2 sparging, the strain produced ∼71 g L(-1) of 1,3-propanediol, whereas under self-generated anaerobiosis, 1,3-propanediol pathway was evidently restricted, as only 30.5 g L(-1) of 1,3-propanediol were finally produced. Apparently, N2 infusion strategy paired with bioreactor geometry can alter the biochemical behavior of the particular strain.


Early dysfunctions of fronto-parietal praxis networks in Parkinson's disease.
In Parkinson's disease (PD) the prevalence of apraxia increases with disease severity implying that patients in early stages may already have subclinical deficits. The aim of this exploratory fMRI study was to investigate if subclinical aberrations of the praxis network are already present in patients with early PD. In previous functional imaging literature only data on basal motor functions in PD exists. Thirteen patients with mild parkinsonian symptoms and without clinically diagnosed apraxia and 14 healthy controls entered this study. During fMRI participants performed a pantomime task in which they imitated the use of visually presented objects. Patients were measured ON and OFF dopaminergic therapy to evaluate a potential medication effect on praxis abilities and related brain functions. Although none of the patients was apraxic according to De Renzi ideomotor scores (range 62-72), patients OFF showed significantly lower praxis scores than controls. Patients exhibited significant hyperactivation in left fronto-parietal core areas of the praxis network. Frontal activations were clearly dominant in patients and were correlated with lower individual praxis scores. We conclude that early PD patients already show characteristic signs of praxis network dysfunctions and rely on specific hyperactivations to avoid clinically evident apraxic symptoms. Subclinical apraxic deficits were shown to correlate with an activation shift from left parietal to left frontal areas implying a prospective individual imaging marker for incipient apraxia.


Solution and solid-phase synthesis of potent inhibitors of hepatitis C virus NS3 proteinase.
A versatile route for the synthesis of homochiral alpha-ketoamide analogues of amino acids is described. Incorporation of this functionality into peptide sequences using either solution or solid-phase chemistry resulted in potent inhibitors of the Hepatitis C Virus NS3 proteinase.


Promoting enjoyment and self-belief through work rehabilitation.
There has been a resurgence of interest in work rehabilitation in recent years. A variety of service models are in operation in a number of countries, all, to varying degrees, assisting mental-health clients achieve an optimum level of employment participation. However, little research has been conducted to examine how (and if) such schemes are structured to promote psycosocial rehabilitation. To explore such issues, the author carried out a pilot case study of a work-rehabilitation organization in Lincolnshire, United Kingdom. Two of the main themes, that emerged during the study, Hedonic Experiences and Self-Efficacy, are discussed in this article.


Synthesis and contractile activity of new acetylenic and allenic analogues of leukotrienes C4 and D4: importance of the Z-11,12 double bond.
The (5S,6R) isomers of new acetylenic and allenic analogues of leukotrienes C4 and D4 were synthesized for comparative pharmacological studies on intestinal smooth muscle preparations. These new analogues are poor spasmogenic agonists, the replacement of the 11,12-ene with a relatively more stable triple bond causing an important reduction in intrinsic activity. They did not show any significant antagonist activity. Unexpectedly, these results prove that the 11,12 portion in the triene structure of the lipophilic chain is critical for an agonist activity.


Infra-red and Raman spectroscopic study of tetra-substituted bis(phthalocyaninato) rare earth complexes peripherally substituted with tert-butyl derivatives.
The infra-red spectroscopic data for a series of 13 homoleptic substituted bis(phthalocyaninato) rare earth complexes with tervalent rare earths M(III)(TBPc)(2) [M=Y, Pr, ..., Lu except La, Ce and Pm; TBPc=dianion of 3(4),12(13),21(22),30(31)-tetra(tert-butyl)-phthalocyanine] have been collected with resolution of 2 cm(-1). Raman spectroscopic properties in the range of 500-1,800 cm(-1) for these double-deckers M(III)(TBPc)(2) have been collected using laser excitation sources emitting at 632.8 nm. Both the IR and Raman spectra for M(III)(TBPc)(2) are more complicated than those of homoleptic bis(phthalocyaninato) rare earth analogues due to the decreased molecular symmetry of these double-decker compounds. For this series, the IR typical marker band of (TBPc)(-) appears as an intense absorption at 1,314-1,319 cm(-1), attributed to the pyrrole stretching. Under excitation at 632.8 nm that is in close resonance with the main Q absorption band of phthalocyanine ligand, typical Raman marker band of the monoanion radical (TBPc)(-) was observed at 1,515-1,530 cm(-1) resulting from aza CN stretching. Both techniques reveal that the frequencies of pyrrole stretching, isoindole breathing and aza stretchings depend on the rare earth ionic size, shifting to higher energy along with the lanthanide contraction due to the increased ring-ring interaction across the series.