Effects of grape seed extract, lutein, and fish oil on responses of canine lens epithelial cells in vitro.
OBJECTIVE To determine the effects of grape seed extract (GSE), lutein, and fish oil containing omega-3 fatty acids on oxidative stress, migration, proliferation, and viability of lens epithelial cells (LECs). SAMPLE Lens capsules or cultured LECs obtained from canine cadavers. PROCEDURES An antioxidant reductive capacity assay was used to determine reducing capability of each substance. The LECs were cultured and incubated with various substances, including N-acetyl cysteine (NAC), when appropriate, and dimethyl sulfoxide (DMSO) as positive and vehicle control substances, respectively. A dichlorofluorescein assay was used to evaluate reactive oxygen species (ROS) production, and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to determine cell viability. Ex vivo posterior capsule opacification (PCO) was used to evaluate LEC migration and proliferation. RESULTS Antioxidant reductive effects of GSE surpassed those of NAC, lutein, and fish oil containing omega-3 fatty acids. The GSE reduced ROS production in LECs, compared with the DMSO vehicle control, whereas lutein was pro-oxidative. All test substances reduced cell viability. Ex vivo PCO was not altered by GSE, was decreased by lutein, and was increased by fish oil containing omega-3 fatty acids, compared with results for the DMSO vehicle control. CONCLUSIONS AND CLINICAL RELEVANCE Only GSE had significant antioxidant capabilities and reduced ROS production; however, no effect on ex vivo PCO was detected. Fish oil containing omega-3 fatty acids increased ex vivo PCO. No conclusions could be made regarding antioxidant effects of these substances on LECs. These findings suggested that the substances will not decrease PCO.


An integrated passive micromixer-magnetic separation-capillary electrophoresis microdevice for rapid and multiplex pathogen detection at the single-cell level.
Here we report an integrated microdevice consisting of an efficient passive mixer, a magnetic separation chamber, and a capillary electrophoretic microchannel in which DNA barcode assay, target pathogen separation, and barcode DNA capillary electrophoretic analysis were performed sequentially within 30 min for multiplex pathogen detection at the single-cell level. The intestine-shaped serpentine 3D micromixer provides a high mixing rate to generate magnetic particle-pathogenic bacteria-DNA barcode labelled AuNP complexes quantitatively. After magnetic separation and purification of those complexes, the barcode DNA strands were released and analyzed by the microfluidic capillary electrophoresis within 5 min. The size of the barcode DNA strand was controlled depending on the target bacteria (Staphylococcus aureus, Escherichia coli O157:H7, and Salmonella typhimurium), and the different elution time of the barcode DNA peak in the electropherogram allows us to recognize the target pathogen with ease in the monoplex as well as in the multiplex analysis. In addition, the quantity of the DNA barcode strand (∼10(4)) per AuNP is enough to be observed in the laser-induced confocal fluorescence detector, thereby making single-cell analysis possible. This novel integrated microdevice enables us to perform rapid, sensitive, and multiplex pathogen detection with sample-in-answer-out capability to be applied for biosafety testing, environmental screening, and clinical trials.


Relapsing MS patients' experiences with glatiramer acetate treatment: a phenomenological study.
This study examined the experiences of a group of patients with relapsing multiple sclerosis who received glatiramer acetate for the treatment of their illness. Heideggerian phenomenologic research methods drove the data analysis process with the Atlas Qualitative Data Analysis software program. The sample was a diverse group of 20 men and women 39-64 years of age who had been diagnosed with MS 1-21 years and taking glatiramer acetate 1-7 years. Several participants had been on other treatments; they related their reasons for choosing this treatment and how they manage to persist with taking the daily injections. The themes included choosing glatiramer acetate, self-managing care, injecting, healthy lifestyle, side effects, support, and participant advice to others. Patients with relapsing MS experience a complex process of adjustment when they are diagnosed with the disease and come to the decision to start aggressively treating the illness. They view glatiramer acetate as an integral part of the formula to maintain control over their bodies and manage the disease. Taking the glatiramer acetate injection every day becomes easier as time goes on. They reported that side effects were minimal and manageable.


Early prediction of medication refractoriness in children with idiopathic epilepsy based on scalp EEG analysis.
Refractory epilepsy often has deleterious effects on an individual's health and quality of life. Early identification of patients whose seizures are refractory to antiepileptic drugs is important in considering the use of alternative treatments. Although idiopathic epilepsy is regarded as having a significantly lower risk factor of developing refractory epilepsy, still a subset of patients with idiopathic epilepsy might be refractory to medical treatment. In this study, we developed an effective method to predict the refractoriness of idiopathic epilepsy. Sixteen EEG segments from 12 well-controlled patients and 14 EEG segments from 11 refractory patients were analyzed at the time of first EEG recordings before antiepileptic drug treatment. Ten crucial EEG feature descriptors were selected for classification. Three of 10 were related to decorrelation time, and four of 10 were related to relative power of delta/gamma. There were significantly higher values in these seven feature descriptors in the well-controlled group as compared to the refractory group. On the contrary, the remaining three feature descriptors related to spectral edge frequency, kurtosis, and energy of wavelet coefficients demonstrated significantly lower values in the well-controlled group as compared to the refractory group. The analyses yielded a weighted precision rate of 94.2%, and a 93.3% recall rate. Therefore, the developed method is a useful tool in identifying the possibility of developing refractory epilepsy in patients with idiopathic epilepsy.


Scleromyxedema associated with esophageal aperistalsis and dermal eosinophilia.
Scleromyxedema (generalized lichen myxedematosus) is a rare variant of papular mucinosis characterized clinically by generalized waxy papules and marked cutaneous induration. Histologically, there is fibromucinous infiltration of the superficial dermis. Most patients also have had a monoclonal serum protein of cathodal mobility. The case to be presented is remarkable for the following reasons: 1. the presence of esophageal aperistalsis; 2. the presence of prominent dermal eosinophilia; and 3. the absence of a serum monoclonal paraprotein.


Uncorrected Refractive Error and Distance Visual Acuity in Children Aged 6 to 14 Years.
This study presents the relationship between distance visual acuity and a range of uncorrected refractive errors, a complex association that is fundamental to clinical eye care and the identification of children needing refractive correction. This study aimed to analyze data from the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study to describe the relationship between distance uncorrected refractive error and visual acuity in children. Subjects were 2212 children (51.2% female) 6 to 14 years of age (mean ± standard deviation, 10.2 ± 2.1 years) participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study between 2000 and 2010. Uncorrected distance visual acuity was measured using a high-contrast projected logMAR chart. Cycloplegic refractive error was measured using the Grand Seiko WR-5100K autorefractor. The ability of logMAR acuity to detect various categories of refractive error was examined using receiver operating characteristic curves. Isoacuity curves show that increasing myopic spherical refractive errors, increasing astigmatic refractive errors, or a combination of both reduces distance visual acuity. Visual acuity was reduced by approximately 0.5 minutes of MAR per 0.30 to 0.40 D of spherical refractive error and by approximately 0.5 minutes of MAR per 0.60 to 0.90 D of astigmatism. Higher uncorrected hyperopic refractive error had little effect on distance visual acuity. Receiver operating characteristic curve analysis suggests that a logMAR distance acuity of 0.20 to 0.32 provides the best balance between sensitivity and specificity for detecting refractive errors other than hyperopia. Distance acuity alone was ineffective for detecting hyperopic refractive errors. Higher myopic and/or astigmatic refractive errors were associated with predictable reductions in uncorrected distance visual acuity. The reduction in acuity per diopter of cylindrical error was about half that for spherical myopic error. Although distance acuity may be a useful adjunct to the detection of myopic spherocylindrical refractive errors, accommodation presumably prevents acuity from assisting in the detection of hyperopia. Alternate procedures need to be used to detect hyperopia.


Prehospital Mass Casualty Incident Response to a Fire in a Nursing Home in Milan, Italy: Actions Taken and Shortcomings.
On July 7, 2023, at 1:21 am, a fire was declared in a retirement home in Milan, Italy. The number of casualties (n = 87) according to the Simple Triage and Rapid Treatment (START) triage system was categorized as 65 green, 14 yellow, 2 red, and 6 black; 75% were women, and the mean age was 85.1 years (± 9). Most patients were unable to walk. A total of 30 basic life support (BLS) ambulances, 3 advanced cardiac life support (ACLS) teams on fast cars, 2 buses, and 1 coordination team were deployed. A scoop and run approach was adopted with patients being transported to 15 health care facilities. The event was terminated at 5:43 am. Though the local mass casualty incident (MCI) response plan was correctly applied, the evacuation of the building was difficult due to the age and comorbidities of the patients. START failed to correctly identify patients categorized as minor. Communication problems arose on site that led to the late evacuation of critical patients.


Deoxyhypusine Modification of Eukaryotic Translation Initiation Factor 5A (eIF5A) Is Essential for Trypanosoma brucei Growth and for Expression of Polyprolyl-containing Proteins.
The eukaryotic protozoan parasite Trypanosoma brucei is the causative agent of human African trypanosomiasis. Polyamine biosynthesis is essential in T. brucei, and the polyamine spermidine is required for synthesis of a novel cofactor called trypanothione and for deoxyhypusine modification of eukaryotic translation initiation factor 5A (eIF5A). eIF5A promotes translation of proteins containing polyprolyl tracts in mammals and yeast. To evaluate the function of eIF5A in T. brucei, we used RNA interference (RNAi) to knock down eIF5A levels and found that it is essential for T. brucei growth. The RNAi-induced growth defect was complemented by expression of wild-type human eIF5A but not by a Lys-50 mutant that blocks modification by deoxyhypusine. Bioinformatics analysis showed that 15% of the T. brucei proteome contains 3 or more consecutive prolines and that actin-related proteins and cysteine proteases were highly enriched in the group. Steady-state protein levels of representative proteins containing 9 consecutive prolines that are involved in actin assembly (formin and CAP/Srv2p) were significantly reduced by knockdown of eIF5A. Several T. brucei polyprolyl proteins are involved in flagellar assembly. Knockdown of TbeIF5A led to abnormal cell morphologies and detached flagella, suggesting that eIF5A is important for translation of proteins needed for these processes. Potential specialized functions for eIF5A in T. brucei in translation of variable surface glycoproteins were also uncovered. Inhibitors of deoxyhypusination would be expected to cause a pleomorphic effect on multiple cell processes, suggesting that deoxyhypusine/hypusine biosynthesis could be a promising drug target in not just T. brucei but in other eukaryotic pathogens.


Physiologically-Mediated Self/Non-Self Root Discrimination in Trifolium repens has Mixed Effects on Plant Performance.
Recent studies suggest that plant roots can avoid competition with other roots of the same plant, but the mechanism behind this behavior is yet largely unclear and their effects on plant performance hardly studied. We grew combinations of two ramets of Trifolium repens in a single pot that were either intact, disconnected for a shorter or longer time, or that belonged to different genotypes. Interconnected ramets developed lower root length and mass than any other combination of ramets, supporting the notion that self/non-self discrimination in T. repens was based entirely on physiological coordination between different roots that develop on the same plant, rather than biochemical allorecognition. These responses were consistent among eight field-collected genotypes, suggesting that self/non-self discrimination is a common feature in wild populations of white clover. There were no significant treatment x genotype interactions suggesting that genetic variation for self/non-self discrimination may be limited. Self-interactions resulted in lower to similar shoot biomass and number of ramets, but higher flowering probabilities, compared to non-self interactions. Thus, our results demonstrated that the performance consequences of self/non-self discrimination may be more complicated than previously thought.


Antagonizing the α4β1 integrin, but not α4β7, inhibits leukocytic infiltration of the central nervous system in rhesus monkey experimental autoimmune encephalomyelitis.
The immune system is characterized by the preferential migration of lymphocytes through specific tissues (i.e., tissue tropism). Tissue tropism is mediated, in part, by the α(4) integrins expressed by T lymphocytes. The α(4)β(1) integrin mediates migration of memory T lymphocytes into the CNS, whereas the α(4)β(7) integrin mediates migration preferentially into gastrointestinal tissue. This paradigm was established primarily from investigations in rodents; thus, the objective of this investigation was to determine if blocking the α(4)β(7) integrin exclusively would affect migration of T lymphocytes into the CNS of primates. The effects of the dual α(4)β(1) and α(4)β(7) antagonist natalizumab were compared with those of the α(4)β(7) antagonist vedolizumab on experimental autoimmune encephalomyelitis in the rhesus monkey. Animals received an initial i.v. bolus of placebo, natalizumab (30 mg/kg), or vedolizumab (30 mg/kg) before intracutaneous immunization with recombinant human myelin oligodendrocyte glycoprotein and then Ab once weekly thereafter. Natalizumab prevented CNS inflammation and demyelination significantly (p < 0.05), compared with time-matched placebo control animals, whereas vedolizumab did not inhibit these effects, despite saturating the α(4)β(7) integrin in each animal for the duration of the investigation. These results demonstrate that blocking α(4)β(7) exclusively does not inhibit immune surveillance of the CNS in primates.


Ultrafast gaseous "half-wave plate".
We demonstrate that filaments generated by ultrashort laser pulses can induce a remarkably large birefringence in Argon over its whole length, resulting in an ultrafast "half-wave plate" for a copropagating probe beam. This birefringence originates from the difference between the nonlinear refractive indices induced by the filament on the axes parallel and orthogonal to its polarization. An angle of 45 degrees between the filament and the probe polarizations allows the realization of ultrafast Kerr-gates, with a switching time ultimately limited by the duration of the filamenting pulse.


Expression and purification of the cynR regulatory gene product: CynR is a DNA-binding protein.
The CynR protein, a member of the LysR family, positively regulates the Escherichia coli cyn operon and negatively autoregulates its own transcription. By S1 mapping analysis, the in vivo cynR transcription start site was located 63 bp upstream of the cynTSX operon transcription start site. Topologically, the cynR and cynTSX promoters overlap and direct transcription in opposite directions. The CynR translation initiation codon was identified by oligonucleotide-directed mutagenesis, and the CynR coding sequence was cloned under the control of a T7 phage promoter. The CynR protein was stably expressed at a high level with a T7 RNA polymerase-T7 phage promoter system. Purification by ion-exchange chromatography, affinity chromatography, and ammonium sulfate fractionation yielded pure CynR protein. Gel shift assays confirmed that CynR is a DNA-binding protein like the other members of the LysR family. The CynR regulatory protein binds specifically to a 136-bp DNA fragment encompassing both the cynR and the cynTSX promoters.


Small molecule modulation of p75 neurotrophin receptor functions.
Ligand-independent and/or proNGF-induced p75(NTR) signaling has emerged as a potential major contributor to a number of pathological states, including axotomy-induced death, motor neuron degeneration, neuronal degeneration in Alzheimer's disease and oligodendrocyte death following spinal cord injury. A long standing goal in the neurotrophin field has been the development of non-peptide, small molecules capable of functioning as specific ligands at neurotrophin receptors such as p75(NTR) to promote desired biological outcomes. Synthetic peptides modeled on neurotrophin protein domains have been found to bind to and activate various neurotrophin receptors, raising the possibility that active, non-peptide, small molecule ligands might also be identified; however, traditional high-throughput screening approaches have been largely ineffective in identifying such compounds. Using pharmacophores derived from the structure of loop 1 of nerve growth factor, non-peptide, small molecules that function as p75(NTR) ligands to promote survival and block proNGF-induced death have recently been identified. Small molecule p75(NTR) ligands, with high potency and specificity, may provide novel therapeutic approaches for neurodegenerative diseases, neurotrauma and other pathologic states.


Hydrogen Sulfide Prevents and Partially Reverses Ozone-Induced Features of Lung Inflammation and Emphysema in Mice.
Hydrogen sulfide (H2S), a novel signaling gasotransmitter in the respiratory system, may have antiinflammatory properties in the lung. We examined the preventive and therapeutic effects of H2S on ozone-induced features of lung inflammation and emphysema. C57/BL6 mice were exposed to ozone or filtered air over 6 weeks. Sodium hydrogen sulfide (NaHS), an H2S donor, was administered to the mice either before ozone exposure (preventive effect) or after completion of 6 weeks of ozone exposure (therapeutic effect). The ozone-exposed mice developed emphysema, measured by micro-computed tomography and histology, airflow limitation, measured by the forced maneuver system, and increased lung inflammation with augmented IL-1β, IL-18, and matrix metalloproteinase-9 (MMP-9) gene expression. Ozone-induced changes were associated with increased Nod-like receptor pyrin domain containing 3 (NLRP3)-caspase-1 activation and p38 mitogen-activated protein kinase phosphorylation and decreased Akt phosphorylation. NaHS both prevented and reversed lung inflammation and emphysematous changes in alveolar space. In contrast, NaHS prevented, but did not reverse, ozone-induced airflow limitation and bronchial structural remodeling. In conclusion, NaHS administration prevented and partially reversed ozone-induced features of lung inflammation and emphysema via regulation of the NLRP3-caspase-1, p38 mitogen-activated protein kinase, and Akt pathways.


Alcoholism and major depression in women. A twin study of the causes of comorbidity.
Although major depression (MD) and alcoholism co-occur in clinical and epidemiologic samples of women more often than expected by chance, the magnitude and causes of this comorbidity are uncertain. Personal interviews were conducted with 2163 female twins from a population-based twin registry. Bivariate twin analysis was performed using two definitions of MD and three definitions of alcoholism of varying diagnostic breadth. Odds ratios ranged from 2.7 to 6.0 and were consistently higher using narrower diagnostic criteria for either disorder. Twin analyses found (1) no evidence for familial environmental factors for either MD or alcoholism; (2) significant genetic correlations, ranging from +.4 to +.6, between MD and alcoholism, which were higher using narrower criteria for alcoholism; (3) significant individual-specific environmental correlations, ranging from +.2 to +.4, for all but one of the diagnostic combinations, which were higher using narrower criteria for MD. Comorbidity between MD and alcoholism in women is substantial and appears to result largely from genetic factors that influence the risk to both disorders, but common environmental risk factors also contribute. However, genetic factors exist that influence the liability to MD without influencing the risk for alcoholism and vice versa. Narrowing the diagnostic criteria for MD or alcoholism increases comorbidity, but for different reasons narrow diagnostic criteria for MD increase the environmental sources of comorbidity while narrow diagnostic criteria for alcoholism increase the genetic sources of comorbidity.


Focus on vitamin D and the adrenal gland.
The main role of vitamin D is to maintain calcium and phosphorus homeostasis, thus preserving bone health. However, recent evidences have demonstrated that vitamin D may also play a role in a variety of nonskeletal disorders such as endocrine diseases and in particular type 1 diabetes, type 2 diabetes, adrenal diseases, and the polycystic ovary syndrome. Despite controversial results on an association of low vitamin D levels with cortisol and aldosterone overproduction, encouraging in vitro findings have been reported on vitamin D effects in adrenocortical cancer cells. The focus of this review is the role of vitamin D in adrenal diseases and the results of vitamin D supplementation studies in patients. Although many studies support a beneficial role of vitamin D in adrenal disease, randomized controlled trials and mechanistic studies are required to provide more insight into the efficacy and safety of vitamin D as a therapeutic tool.


Arabidopsis AtSerpin1, crystal structure and in vivo interaction with its target protease RESPONSIVE TO DESICCATION-21 (RD21).
In animals, protease inhibitors of the serpin family are associated with many physiological processes, including blood coagulation and innate immunity. Serpins feature a reactive center loop (RCL), which displays a protease target sequence as a bait. RCL cleavage results in an irreversible, covalent serpin-protease complex. AtSerpin1 is an Arabidopsis protease inhibitor that is expressed ubiquitously throughout the plant. The x-ray crystal structure of recombinant AtSerpin1 in its native stressed conformation was determined at 2.2 A. The electrostatic surface potential below the RCL was found to be highly positive, whereas the breach region critical for RCL insertion is an unusually open structure. AtSerpin1 accumulates in plants as a full-length and a cleaved form. Fractionation of seedling extracts by nonreducing SDS-PAGE revealed the presence of an additional slower migrating complex that was absent when leaves were treated with the specific cysteine protease inhibitor L-trans-epoxysuccinyl-L-leucylamido (4-guanidino)butane. Significantly, RESPONSIVE TO DESICCATION-21 (RD21) was the major protease labeled with the L-trans-epoxysuccinyl-L-leucylamido (4-guanidino)butane derivative DCG-04 in wild type extracts but not in extracts of mutant plants constitutively overexpressing AtSerpin1, indicating competition. Fractionation by nonreducing SDS-PAGE followed by immunoblotting with RD21-specific antibody revealed that the protease accumulated both as a free enzyme and in a complex with AtSerpin1. Importantly, both RD21 and AtSerpin1 knock-out mutants lacked the serpin-protease complex. The results establish that the major Arabidopsis plant serpin interacts with RD21. This is the first report of the structure and in vivo interaction of a plant serpin with its target protease.


Public health guidelines should recommend reducing saturated fat consumption as much as possible: Debate Consensus.
There is ongoing debate as to whether public health guidelines should advocate reducing SFA consumption as much as possible to reduce the risk of chronic diseases, especially cardiovascular disease (CVD). In considering both sides of this question, we identified a number of points of agreement, most notably that the overall dietary patterns in which SFAs are consumed are of greater significance for cardiometabolic and general health than SFA intake alone. Nevertheless, there remained significant disagreements, centered largely on the interpretation of evidence bearing on 4 major questions: 1) does reducing dietary SFAs lower the incidence of CVD, 2) is the LDL-cholesterol reduction with lower SFA intake predictive of reduced CVD risk, 3) do dietary SFAs affect factors other than LDL cholesterol that may impact CVD risk, and 4) is there a sufficient rationale for setting a target for maximally reducing dietary SFAs? Finally, we identified specific research needs for addressing knowledge gaps that have contributed to the controversies.


Arthroscopic repair of humeral avulsion of glenohumeral ligament lesion: anterior and posterior techniques.
Humeral avulsion of the inferior glenohumeral ligament complex is an unusual pathology, often implicated in traumatic shoulder instability. Traditional open techniques involve at least partial detachment of the subscapularis, and arthroscopic techniques are limited by neurovascular boundaries. The technique described here presents an anterior and posterior arthroscopic approach that can be used individually or in combination to treat different types of humeral avulsion of the inferior glenohumeral ligament lesions. The anterior approach is based on anatomic guidelines described in the literature. The posterior approach is based on the arthroscopic and cadaveric anatomic studies described by one of the authors (D.N.B.); use of the recently described axillary pouch portal (Bhatia portal) permits safe arthroscopic instrumentation access in the entire inferior glenohumeral recess and provides adequate access to the posteroinferior aspect of the humeral head. The differential mattress stitch technique ensures secure fixation of the avulsed ligaments and eliminates excessive capsular redundancy. Technical tips to avoid complications are discussed, and a detailed rehabilitation protocol is presented.


Functional and structural properties of pyridoxal reductase (PdxI) from Escherichia coli: a pivotal enzyme in the vitamin B6 salvage pathway.
Pyridoxine 4-dehydrogenase (PdxI), a NADPH-dependent pyridoxal reductase, is one of the key players in the Escherichia coli pyridoxal 5'-phosphate (PLP) salvage pathway. This enzyme, which catalyses the reduction of pyridoxal into pyridoxine, causes pyridoxal to be converted into PLP via the formation of pyridoxine and pyridoxine phosphate. The structural and functional properties of PdxI were hitherto unknown, preventing a rational explanation of how and why this longer, detoured pathway occurs, given that, in E. coli, two pyridoxal kinases (PdxK and PdxY) exist that could convert pyridoxal directly into PLP. Here, we report a detailed characterisation of E. coli PdxI that explains this behaviour. The enzyme efficiently catalyses the reversible transformation of pyridoxal into pyridoxine, although the reduction direction is thermodynamically strongly favoured, following a compulsory-order ternary-complex mechanism. In vitro, the enzyme is also able to catalyse PLP reduction and use NADH as an electron donor, although with lower efficiency. As with all members of the aldo-keto reductase (AKR) superfamily, the enzyme has a TIM barrel fold; however, it shows some specific features, the most important of which is the presence of an Arg residue that replaces the catalytic tetrad His residue that is present in all AKRs and appears to be involved in substrate specificity. The above results, in conjunction with kinetic and static measurements of vitamins B6 in cell extracts of E. coli wild-type and knockout strains, shed light on the role of PdxI and both kinases in determining the pathway followed by pyridoxal in its conversion to PLP, which has a precise regulatory function.


Induced gonadotropin release in adrenocorticotropin-treated bulls and steers.
The effect of adrenocorticotropin hormone (ACTH) on plasma cortisol and on gonadotropin releasing hormone (GnRH)-induced release of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone was determined in nine Holstein bulls and 12 Holstein steers. Treatments consisted of animals receiving either GnRH (200 micrograms, Group G), ACTH (.45 IU/kg BW, Group A) or a combination of ACTH followed 2 h later by GnRH (Group AG). Group G steers and bulls had elevated plasma LH and FSH within .5 h after GnRH injection and plasma testosterone was increased by 1 h after GnRH injection in bulls. In Group A, plasma cortisol was elevated by .5 h after ACTH injection in both steers and bulls, but plasma LH and FSH were unaffected. In Group A bulls, testosterone was reduced after ACTH injection. In Group AG, ACTH caused an immediate increase in plasma cortisol in both steers and bulls, but did not affect the increase in either plasma LH or FSH in response to GnRH in steers. In Group AG bulls, ACTH did not prevent an increase in either plasma LH, FSH or testosterone in response to GnRH compared with basal concentrations. However, magnitude of systemic FSH response was reduced compared with response in Group G bulls, but plasma LH and testosterone were not reduced. The results indicate that ACTH caused an increase in plasma cortisol, but did not adversely affect LH or FSH response to GnRH in steers and bulls. Further, while testosterone was decreased after ACTH alone, neither ACTH nor resulting increased plasma cortisol resulted in decreased testosterone production in the bull after GnRH stimulation.


Function and survival of renal allografts from the same donor transplanted into kidney-only or kidney-pancreas recipients.
The aim of this study was to assess whether kidney-pancreas transplantation (KPT) compromises the prognosis of kidney transplantation (KT). This study included 368 paired recipients who received grafts from the same donor (184 KPT/184 KT), i.e., renal grafts with the same pretransplant functional and pathologic characteristics. KPT recipients (KPR) were significantly younger and included fewer African-Americans (22% vs. 6%, P=0.0005) than recipients of kidney alone (KR). During year 1 after transplant surgery, KPR were re-admitted more often than KR (4.2+/-2 vs. 2.8+/-2, P < 0.0001). The number of acute rejections (AR) and the serum creatinine were not significantly different in KR and KPR up to 3 years after transplant. After 44+/-29 months, 13% of KR and 17% of KPR died (NS), and 17% of KR and 16% of KPR lost their kidneys (NS). In KPR, reduced renal graft survival did not correlate with AR (P=0.44), but it correlated with: older donors, younger recipients, elevated serum creatinine at 6 months, pancreas loss, and the number of episodes of acute graft dysfunction evaluated by biopsy (multivariate analysis). By Cox, graft and patient survival were not significantly different in KR and KPR. However, the patient survival of KPR < 40 years of age was lower than that of KR (P=0.02). Renal biopsies (n=165) in 40 paired recipients showed no significant differences in AR, interstitial fibrosis, or vascular pathology. Renal graft function, structure, and survival are not different in KPR and KR, but the correlates of renal graft survival are different in these two groups of recipients.


Gender differentials in tuberculosis: the role of socio-economic and cultural factors.
This paper reviews current knowledge about the role that socio-economic and cultural factors play in determining gender differentials in tuberculosis (TB) and tuberculosis control. The studies reviewed suggest that socio-economic and cultural factors may be important in two ways: first, they may play a role in determining overall gender differences in rates of infection and progression to disease, and second, they may lead to gender differentials in barriers to detection and successful treatment of TB. Both have implications for successful TB control programmes. The literature reviewed in this paper suggests the following: Gender differentials in social and economic roles and activities may lead to differential exposure to tuberculosis bacilli; The general health/nutritional status of TB-infected persons affects their rate of progression to disease. In areas where women's health is worse than men's (especially in terms of nutrition and human immunodeficiency virus status), women's risk of disease may be increased; A number of studies suggest that responses to illness differ in women and men, and that barriers to early detection and treatment of TB vary (and are probably greater) for women than for men. Gender differences also exist in rates of compliance with treatment; The fear and stigma associated with TB seems to have a greater impact on women than on men, often placing them in an economically or socially precarious position. Because the health and welfare of children is closely linked to that of their mothers, TB in women can have serious repercussions for families and households. The review points to the many gaps that exist in our knowledge and understanding of gender differentials in TB and TB control, and argues for increased efforts to identify and address gender differentials in the control of TB.


Caries-preventive effectiveness of a fluoride varnish: a randomized controlled trial in adolescents with fixed orthodontic appliances.
The aim was to evaluate the efficacy of topical fluoride varnish applications on white spot lesion (WSL) formation in adolescents during treatment with fixed orthodontic appliances. The study design was a double-blinded randomized placebo-controlled trial with two parallel arms. The subjects were 273 consecutive 12- to 15-year-old children referred for maxillary treatment with fixed orthodontic appliances. The patients were randomly assigned to a test or a control group with topical applications of either a fluoride varnish (Fluor Protector) or a placebo varnish every 6th week during the treatment period. The outcome measures at debonding were incidence and progression of WSL on the upper incisors, cuspids and premolars as scored from digital photographs by 2 independent examiners. The attrition rate was 5%. The mean number of varnish applications was 10 (range 4-20) in both groups. The incidence of WSL during the treatment with fixed appliances was 7.4% in the fluoride varnish compared to 25.3% placebo group (p < 0.001). The mean progression score was significantly lower in the fluoride varnish group than in the placebo group, 0.8 +/- 2.0 vs. 2.6 +/- 2.8 (p < 0.001). The absolute risk reduction was 18% and the number needed to treat was calculated to 5.5. The results from the present study strongly suggest that regular topical fluoride varnish applications during treatment with fixed appliances may reduce the development of WSL adjacent to the bracket base. Application of fluoride varnish should be advocated as a routine measure in orthodontic practice.


Using the Internet to teach melanoma management guidelines to primary care physicians.
The aim of this study was to determine whether a brief Internet-based education programme could improve physicians' abilities to manage pigmented skin lesions. A pre-test-post-test assessment was used of subjects' knowledge of skin cancer, confidence in their management abilities and actual ability to recommend appropriate treatment for 20 hypothetical patients with pigmented skin lesions. The setting was the general medicine service of an academic medical centre. Seventeen volunteer medical students, house officers and faculty members took part in the study. Following the pre-test, subjects completed a 1-hour computer-based educational programme, distributed via the Internet, presenting a guideline for recognizing and managing potentially malignant pigmented skin lesions. The guideline was based on the ABCD rule and the Glasgow seven-point checklist. The educational programme had a positive effect on the subjects' overall skin cancer knowledge and had significantly positive effects on their confidence and ability to apply the management guideline. Based on the guideline criteria, the subjects made the correct management decision on the clinical scenarios 63.2% of the time before the programme and 74.1% of the time after the programme (P = 0.002). We were able to teach melanoma management guidelines to physicians and medical students using a brief, interactive computer programme distributed via the Internet. Such an approach is more cost-effective than classroom teaching and could be used to improve the clinical skills of practising physicians to recognize and manage early melanomas. This approach to distributed learning could also be used to teach other clinical guidelines to physicians.


Burn Patients Infected With Metallo-Beta-Lactamase-Producing Pseudomonas aeruginosa: Multidrug-Resistant Strains.
Metallo-beta-lactamase (MBL) producing Pseudomonas aeruginosa in the burn patients is a leading cause of morbidity and mortality and remains a serious health concern among the clinicians. The aim of this study was to detect MBL-producing P. aeruginosa in burn patients and determine multidrug-resistant (MDR) strains, and respective resistance patterns. In this cross-sectional study, 270 strains of P. aeruginosa were isolated from the burn patients referred to Ghotbeddin Burn Hospital, Shiraz, Iran. Among them, 55 MBL-producing P. aeruginosa strains were isolated from 55 patients hospitalized in burn unit. Minimum inhibitory concentrations (MICs) and MBLs were determined by the E-test method. Of the 55 burn cases, 29 (53%) were females and 26 (47%) males. Injured burn patients' ages ranged from 16 to 87 years, with maximum number of cases in the age group of 16 to 36 years (n, 40; 72.7%). Overall, 32 cases were accidental (60%), and 22 were suicidal burns (40%). Of the 55 burn patients, 17 cases were expired (30%). All deaths were due to chemical exposures. In antibiotic susceptibility testing by E-test method, ceftazidime was the most effective one and 35 isolates (63.5%) were resistant to all the 11 tested antibiotics. Routine microbiological surveillance and careful in vitro testing of antibiotics prior to prescription and strict adherence to hospital antibiotic policy may help to prevent, treat, and control MDR and pandrug-resistant (PDR) P. aeruginosa strains in burn units.


Changes in Physician Recommendations for Early Physical Activity After Pediatric Concussion: A Retrospective Study.
This study aimed to analyze changes in physical activity (PA) recommendations after pediatric concussions and examine the associations of patient and injury characteristics with physicians' PA recommendations. Retrospective observational study. Concussion clinics associated with a pediatric hospital. Patients aged 10 to 18 years with a concussion diagnosis, presenting to the concussion clinic within 14 days of the injury were included. A total of 4727 pediatric concussions and corresponding 4727 discharge instructions were analyzed. The independent variables for our study were time, injury characteristics (eg, mechanism and symptom scores), and patient characteristics (eg, demographics and comorbidities). Physician PA recommendations. From 2012 to 2019, the proportion of physicians recommending light activity at an initial visit increased from 11.1% to 52.6% (P < 0.05) within 1-week postinjury and from 16.9% to 64.0% during the second week postinjury (P < 0.05). A significantly increased odds of recommending "light activity" (odds ratio [OR] = 1.82, 95% confidence interval [CI], 1.39-2.40) and "noncontact PA" (OR = 2.21, 95% CI, 1.28-2.05), compared with "no activity" within 1-week postinjury, was observed in each consecutive year. In addition, higher symptom scores at the initial visit were associated with lower likelihood of recommending "light activity" or "noncontact PA." Physician recommendation of early, symptom-limited PA after a pediatric concussion has increased since 2012, which mirrors a shift in acute concussion management. Further research assessing how these PA recommendations may facilitate pediatric concussion recovery is warranted.


Effects of Tear Film Lipid Layer Thickness and Blinking Pattern on Tear Film Instability After Corneal Refractive Surgery.
To investigate associations between changes in tear film instability and the lipid layer thickness (LLT) and blink pattern after corneal refractive surgery (CRS). Forty patients were enrolled in this study. The LLT and blink pattern were evaluated 1 week before and 30 days after CRS using a novel interferometer and an ocular surface disease index (OSDI) questionnaire, and other tear film stability markers were also evaluated. Mean OSDI scores increased from 5.52 to 8.54 (P = 0.016), corneal fluorescence staining scores increased from 0.05 to 0.25 (P = 0.034), first noninvasive tear breakup time (NIBUT-F) decreased from 9.66 to 7.33 seconds (P = 0.014), and average noninvasive tear breakup time (NIBUT-Ave) decreased from 12.32 to 10.26 seconds (P = 0.047) 1 month after CRS. Meanwhile, mean total blink frequency in 20 seconds decreased significantly from 12.62 to 6.31 (P < 0.001); LLT did not change significantly (P = 0.447). The change in NIBUT-Ave was positively correlated with that in LLT (P = 0.003) and negatively correlated with that in the partial blink rate (P = 0.013). The changes in the OSDI questionnaire, NIBUT, LLT, and blink pattern were not different between the laser-assisted in situ keratomileusis and laser-assisted subepithelial keratomileusis groups. A decrease in tear film stability occurs 1 month after CRS, the change in the blink pattern and unchanged LLT preoperatively and postoperatively suggesting that these parameters play a role in maintaining tear film stability after CRS.


Effect of subinhibitory doses of rifaximin on in vitro Pseudomonas aeruginosa adherence and biofilm formation to biotic and abiotic surface models.
The adhesion of Pseudomonas aeruginosa to biotic and abiotic surfaces is responsible for the persistence and development of bacterial infection. To fill the gap in the knowledge regarding the relationship between rifaximin susceptibility and biofilm formation, and to investigate the effect of subinhibitory doses of rifaximin on the adhesion and biofilm formation. A total of 10 isolates of P. aeruginosa were obtained from 110 urine samples of urinary tract infection (UTI) patients. Biofilm formation on polystyrene microtiter plates, minimum inhibitory concentrations (MICs) of rifaximin against the 10 isolates of P. aeruginosa (Pa1-Pa10), the effect of sub-MICs of rifaximin (0.5 × MIC, 0.25 × MIC, 0.125 × MIC, and 0.06 × MIC) on biofilm formation by the Pa4 isolate to polystyrene microtiter plates, and the adhesion to human epithelial cells (HECs) in vitro were evaluated. The MICs of rifaximin against 10 isolates ranged from 62.5 μg/mL to 1000 μg/mL. The Pa4 isolate produced the highest level of biofilm formation, while the MIC of Pa4 was 125 μg/mL. There was no correlation between bacterial susceptibility to rifaximin and biofilm formation (r: -0.016; p > 0.05). Sub-MIC doses of rifaximin significantly reduced the biofilm formation on abiotic surfaces, while only 0.5 × MIC, 0.25 × MIC and 0.12 × MIC of rifaximin reduced the adhesion to HECs significantly (p < 0.05) in a dose-dependent manner. This pioneering study demonstrated the negative effect of sub-MIC doses of rifaximin on biofilm formation and adhesion to abiotic and biotic surfaces in vitro.


Carcinosarcoma of the colon: report of a case with morphological, ultrastructural and molecular analysis.
Carcinosarcoma of the colon is a rare histopathological entity with uncertain histogenesis, that shows both epithelial and mesenchymal malignant differentiation. Carcinosarcoma rarely affects the gastrointestinal tract and only few cases are reported in the colon. Herein we describe a carcinosarcoma of the ascending colon, with morphological, ultrastructural and molecular analysis. An 81-year-old man was hospitalised for asthenia, weight loss and iron-deficiency anaemia. The patient underwent colonoscopy and adenocarcinoma was diagnosed by endoscopic biopsy. A right hemicolectomy was performed and, during surgical operation, liver metastases were detected. Histological examination of the surgical specimen revealed areas of both carcinomatous and sarcomatous differentiation, completely separated by fibrous septae. The sarcomatous component exhibited areas of smooth muscle and osteoblastic differentiation, with focal osteoid material deposition. Molecular analysis conducted separately on the epithelial and mesenchymal components revealed the same p53 gene mutation (R282W in exon 8) and identical polymorphisms in p53 exon 4, in EGFR exons 20 and 21, and in c-kit exon 17. Microsatellite markers analysis revealed a common loss of heterozygosis on 18q. Overall, the data are consistent with a common origin of the two tumor components. The patient was treated with 8 cycles of oral capecitabine (1250 mg/m2 twice a day for 14 days repeated every 28 days) and two years after surgery is alive with liver metastases. Carcinosarcoma of the colon is a rare tumour with both epithelial and sarcomatous components. Molecular analysis of the current case suggests the histogenesis from a common cell progenitor.


A point mutation in the neu1 promoter recruits an ectopic repressor, Nkx3.2 and results in a mouse model of sialidase deficiency.
SM/J is an inbred mouse strain with a complex phenotype including small body size, impaired immune response and a tissue-specific sialidase deficiency. We identified a regulatory mutation, (-519G-->A) within the neu1 promoter which in reporter assays resulted in significantly reduced transcription. This mutation generates a consensus binding site for Nkx3 family transcription repressors. Recombinant Nkx3.2 bound strongly to and preferentially repressed transcription of the mutant promoter. This tissue-specific deficiency results in a retarded immune response and modulates leukocyte recruitment. Examination of the hepatic microcirculation in mutant mice revealed increased rolling and decreased adhesion of leukocytes. Our findings support a significant role for lysosomal sialidase in inflammation and highlight the significance of repressor-recruitment in genetic disease.


Preliminary Study of Axillary Lymphatic Drainage in Cutaneous Melanoma Patients: A Cross-Sectional Study.
Background: The axilla is a region of fundamental importance for the implications during oncological surgery, and there are many classifications of axillary lymph node subdivision: on the basis of studies on women with breast cancer, we used Clough's and Li's classification. However, currently we do not have a gold-standard classification regarding axillary lymphatic drainage in melanoma patients. Purpose: Our aim was to evaluate how these classifications could be adapted to sentinel lymph node evaluation in skin-melanoma patients and to look for a possible correlation between the most recent classifications of axillary lymph node location and Oeslner's classification, one of the most common anatomical classifications still widespread today. Methods: We analyzed data from 21 patients who underwent sentinel lymph node biopsy between January 2021 and January 2022. Results: Our study demonstrates that, to an extent, there is a possible difference in the use of the various classifications, hinting at possible limits of each. The data we obtained underline how cutaneous melanoma presents extremely heterogenous lymphatic drainage at the level of the axillary cavity. However, the limited data in our possession do not allow us to obtain, at the moment, results that are statistically significant, although we are continuing to enroll patients and collect data. Conclusions: Results of this study support the evidence that the common classifications used for breast cancer do not seem to be exhaustive. Therefore, a specific axillary lymph node classification is necessary in skin melanoma patients.


Life cycle assessment of solid waste management strategies in a chlor-alkali production facility.
The waste management of a chlor-alkali and calcium chloride industrial facility from southern Chile was the object of this study. The main solid waste materials generated in these processes are brine sediments and calcium chloride sediments, respectively. Both residues are mixed in the liquid phase and filtered in a press filter, obtaining a final low humidity solid waste, called 'mixed sediments', which is disposed of in an industrial landfill as non-hazardous waste. The aim of the present study was to compare by means of LCA, the current waste management option of the studied chlor-alkali facility, namely landfill disposal, with two new possible options: the reuse of the mixed sediments as mineral additive in compost and the use of brine sediments as an unconventional sorbent for the removal of heavy metals from wastewater. The functional unit was defined as 1 tonne of waste being managed. To perform this evaluation, software SimaPro 7.0 was used, selecting the Ecoindicator 99 and CML 2000 methodologies for impact evaluation. The obtained results indicate that the use of brine sediments as a novel material for the removal of heavy metals from wastewater (scenario 3) presented environmental benefits when compared with the waste management option of sediments landfilling (scenario 1). The avoided environmental loads, generated by the substitution of activated granular carbon and the removal of Cu and Zn from wastewater in the treatment process generated positive environmental impacts, enhancing the environmental performance of scenario 3.


Structural Dynamics of Tropical Moist Forest Gaps.
Gap phase dynamics are the dominant mode of forest turnover in tropical forests. However, gap processes are infrequently studied at the landscape scale. Airborne lidar data offer detailed information on three-dimensional forest structure, providing a means to characterize fine-scale (1 m) processes in tropical forests over large areas. Lidar-based estimates of forest structure (top down) differ from traditional field measurements (bottom up), and necessitate clear-cut definitions unencumbered by the wisdom of a field observer. We offer a new definition of a forest gap that is driven by forest dynamics and consistent with precise ranging measurements from airborne lidar data and tall, multi-layered tropical forest structure. We used 1000 ha of multi-temporal lidar data (2008, 2012) at two sites, the Tapajos National Forest and Ducke Reserve, to study gap dynamics in the Brazilian Amazon. Here, we identified dynamic gaps as contiguous areas of significant growth, that correspond to areas > 10 m2, with height <10 m. Applying the dynamic definition at both sites, we found over twice as much area in gap at Tapajos National Forest (4.8%) as compared to Ducke Reserve (2.0%). On average, gaps were smaller at Ducke Reserve and closed slightly more rapidly, with estimated height gains of 1.2 m y-1 versus 1.1 m y-1 at Tapajos. At the Tapajos site, height growth in gap centers was greater than the average height gain in gaps (1.3 m y-1 versus 1.1 m y-1). Rates of height growth between lidar acquisitions reflect the interplay between gap edge mortality, horizontal ingrowth and gap size at the two sites. We estimated that approximately 10% of gap area closed via horizontal ingrowth at Ducke Reserve as opposed to 6% at Tapajos National Forest. Height loss (interpreted as repeat damage and/or mortality) and horizontal ingrowth accounted for similar proportions of gap area at Ducke Reserve (13% and 10%, respectively). At Tapajos, height loss had a much stronger signal (23% versus 6%) within gaps. Both sites demonstrate limited gap contagiousness defined by an increase in the likelihood of mortality in the immediate vicinity (~6 m) of existing gaps.


An innovative program to provide methodological mentoring and to foster the development of robust research teams for K awardees: RAMP Mentors.
Within the Biostatistics, Epidemiology, and Research Design (BERD) component of the Northwestern University Clinical and Translational Sciences Institute, we created a mentoring program to complement training provided by the associated Multidisciplinary Career Development Program (KL2). Called Research design Analysis Methods Program (RAMP) Mentors, the program provides each KL2 scholar with individualized, hands-on mentoring in biostatistics, epidemiology, informatics, and related fields, with the goal of building multidisciplinary research teams. From 2015 to 2019, RAMP Mentors paired 8 KL2 scholars with 16 individually selected mentors. Mentors had funded/protected time to meet at least monthly with their scholar to provide advice and instruction on methods for ongoing research, including incorporating novel techniques. RAMP Mentors has been evaluated through focus groups and surveys. KL2 scholars reported high satisfaction with RAMP Mentors and confidence in their ability to establish and maintain methodologic collaborations. Compared with other Northwestern University K awardees, KL2 scholars reported higher confidence in obtaining research funding, including subsequent K or R awards, and selecting appropriate, up-to-date research methods. RAMP Mentors is a promising partnership between a BERD group and KL2 program, promoting methodologic education and building multidisciplinary research teams for junior investigators pursuing clinical and translational research.


Dietary antioxidants and Parkinson disease. The Rotterdam Study.
To investigate whether high dietary intake of antioxidants decreases the risk of Parkinson disease (PD). The community-based Rotterdam Study, the Netherlands. The cross-sectional study formed part of a large community-based study in which all participants were individually screened for parkinsonism and were administered a semiquantitative food frequency questionnaire. The study population consisted of 5342 independently living individuals without dementia between 55 and 95 years of age, including 31 participants with PD (Hoehn-Yahr stages 1-3). The odds ratio for PD was 0.5 (95% confidence interval [CI], 0.2-0.9) per 10-mg daily dietary vitamin E intake, 0.6 (95% CI, 0.3-1.3) per 1-mg beta carotene intake, 0.9 (95% CI, 0.4-1.9) per 100-mg vitamin C intake, and 0.9 (95% CI, 0.7-1.2) per 10-mg flavonoids intake, all adjusted for age, sex, smoking habits, and energy intake. The association with vitamin E intake was dose dependent (P for trend = .03). To assess whether the association was different in participants with more advanced disease, we excluded those with PD who had a Hoehn-Yahr stage of 2.5 or 3. This did not fundamentally alter the results. Our data suggest that a high intake of dietary vitamin E may protect against the occurrence of PD.


Efficacy of Δ9 -Tetrahydrocannabinol (THC) Alone or in Combination With a 1:1 Ratio of Cannabidiol (CBD) in Reversing the Spatial Learning Deficits in Old Mice.
Decline in cognitive performance, an aspect of the normal aging process, is influenced by the endocannabinoid system (ECS). Cannabinoid receptor 1 (CB1) signaling diminishes with advancing age in specific brain regions that regulate learning and memory and abolishing CB1 receptor signaling accelerates cognitive aging in mice. We recently demonstrated that prolonged exposure to low dose (3 mg/kg/day) Δ9-tetrahydrocannabinol (THC) improved the cognitive performances in old mice on par with young untreated mice. Here we investigated the potential influence of cannabidiol (CBD) on this THC effect, because preclinical and clinical studies indicate that the combination of THC and CBD often exhibits an enhanced therapeutic effect compared to THC alone. We first tested the effectiveness of a lower dose (1 mg/kg/day) THC, and then the efficacy of the combination of THC and CBD in 1:1 ratio, same as in the clinically approved medicine Sativex®. Our findings reveal that a 1 mg/kg/day THC dose still effectively improved spatial learning in aged mice. However, a 1:1 combination of THC and CBD failed to do so. The presence of CBD induced temporal changes in THC metabolism ensuing in a transient elevation of blood THC levels. However, as CBD metabolizes, the inhibitory effect on THC metabolism was alleviated, causing a rapid clearance of THC. Thus, the beneficial effects of THC seemed to wane off more swiftly in the presence of CBD, due to these metabolic effects. The findings indicate that THC-treatment alone is more efficient to improve spatial learning in aged mice than the 1:1 combination of THC and CBD.


The assembly pathway of the mitochondrial carrier translocase involves four preprotein translocases.
The mitochondrial inner membrane contains preprotein translocases that mediate insertion of hydrophobic proteins. Little is known about how the individual components of these inner membrane preprotein translocases combine to form multisubunit complexes. We have analyzed the assembly pathway of the three membrane-integral subunits Tim18, Tim22, and Tim54 of the twin-pore carrier translocase. Tim54 displayed the most complex pathway involving four preprotein translocases. The precursor is translocated across the intermembrane space in a supercomplex of outer and inner membrane translocases. The TIM10 complex, which translocates the precursor of Tim22 through the intermembrane space, functions in a new posttranslocational manner: in case of Tim54, it is required for the integration of Tim54 into the carrier translocase. Tim18, the function of which has been unknown so far, stimulates integration of Tim54 into the carrier translocase. We show that the carrier translocase is built via a modular process and that each subunit follows a different assembly route. Membrane insertion and assembly into the oligomeric complex are uncoupled for each precursor protein. We propose that the mitochondrial assembly machinery has adapted to the needs of each membrane-integral subunit and that the uncoupling of translocation and oligomerization is an important principle to ensure continuous import and assembly of protein complexes in a highly active membrane.


Medical management of nephrolithiasis in Dallas: update 1987.
With available medical treatment programs a remission of stone disease could be achieved in more than 80 per cent of the patients and a decrease in individual stone formation rate obtained in greater than 90 per cent. The need for stone removal may be reduced dramatically by an effective prophylactic program. There is some evidence that certain stones (even calcareous types) may undergo dissolution in vivo with appropriate therapy. Moreover, properly applied medical treatments may be capable of overcoming nonrenal manifestations as well as preventing new stone formation. Thus, the potential development of bone disease in patients with renal tubular acidosis may be averted by potassium citrate therapy. Despite these advantages it is clear that the medical treatment approach cannot provide total control of the disease. Stone disease generally presents with a surgical problem related to an already formed stone before medical diagnosis and selective treatment may be applied. Some patients, albeit a minority, are recalcitrant to medical treatment no matter how heroic. A satisfactory response to medical treatment requires continued compliance by the patient to the recommended treatment program and a commitment by the physician to provide long-term followup care. There is no cure, only prophylaxis. The increasing ease and decreasing cost of new approaches to stone removal, particularly with the advent of second generation extracorporeal lithotripsy, will undoubtedly cast a continuing uncertainty on the need for medical diagnosis and treatment. Several factors might influence the choice between surgical and medical approaches. One factor is the severity of stone disease. Patients with repeated episodes of stone formation might be more likely to adopt preventive therapy, whereas those with infrequent stone episodes may elect simply to have them removed upon their occurrence without medical treatment between episodes. Also, the possibility that lithotripsy may cause long-term hazards (for example development of hypertension) must be clarified. Another factor is the occurrence of extrarenal manifestations. In patients suffering from systemic disorders in which nephrolithiasis is only 1 manifestation (for example distal renal tubular acidosis) a medical approach may be justified exclusive of effects on stone formation. Finally, one must consider the relative practicality and cost between stone removal and a medical approach. It is likely that improvements and reductions in costs will occur with both approaches. It is hoped that urologists and internists work jointly to find an appropriate balance between the 2 approaches.(ABSTRACT TRUNCATED AT 400 WORDS)


The parkin mutant phenotype in the fly is largely rescued by metal-responsive transcription factor (MTF-1).
The gene for Parkin, an E3 ubiquitin ligase, is mutated in some familial forms of Parkinson's disease, a severe neurodegenerative disorder. A homozygous mutant of the Drosophila ortholog of human parkin is viable but results in severe motoric impairment including an inability to fly, female and male sterility, and a decreased life span. We show here that a double mutant of the genes for Parkin and the metal-responsive transcription factor 1 (MTF-1) is not viable. MTF-1, which is conserved from insects to mammals, is a key regulator of heavy metal homeostasis and detoxification and plays additional roles in other stress conditions, notably oxidative stress. In contrast to the synthetic lethality of the double mutant, elevated expression of MTF-1 dramatically ameliorates the parkin mutant phenotype, as evidenced by a prolonged life span, motoric improvement including short flight episodes, and female fertility. At the cellular level, muscle and mitochondrial structures are substantially improved. A beneficial effect is also seen with a transgene encoding human MTF-1. We propose that Parkin and MTF-1 provide complementary functions in metal homeostasis, oxidative stress and other cellular stress responses. Our findings also raise the possibility that MTF-1 gene polymorphisms in humans could affect the severity of Parkinson's disease.


Identification of candidate amino acids involved in the formation of pink-red pigments in onion (Allium cepa L.) juice and separation by HPLC.
The formation of pink-red pigments ("pinking") by various amino acids was investigated by reacting amino acids with compounds present in onion juice. The unknown pink-red pigments were generated and separated using high-performance liquid chromatography (HPLC) and a diode array detector (DAD) in the range of 200 to 700 nm. To generate pink-red pigments, we developed several reaction systems using garlic alliinase, purified 1-propenyl-L-cysteine sulfoxide (1-PeCSO), onion thiosulfinate, natural onion juice, and 21 free amino acids. The compound 1-PeCSO was a key compound associated with pinking in the presence of both the alliinase and amino acids. Numerous naturally occurring pink-red pigments were detected and separated from pink onion juice using the HPLC-DAD system at 515 nm. Most free amino acids, with the exceptions of histidine, serine, and cysteine, formed various pink-red pigments when reacted with onion thiosulfinate. This observation indicated that onion pinking is caused not by a single pigment, but by many. Furthermore, more than one color compound could be produced from a single amino acid; this explains, in part, why there were many pink-red compound peaks in the chromatogram of discolored natural onion juice. We presumed that the complexity of the pink-red pigments was due to the involvement of more than 21 natural amino acids as well as several derivatives of the color products produced from each amino acid. We observed that the pinking process in onion juice is very similar to that of the greening process in crushed garlic, emphasizing that both thiosulfinate from flavor precursors and free amino acids are absolutely required for the discoloration.


Gamma-glutamyl transferase: the silent partner?
Glutathione is one of the most abundant proteins in vivo involved in maintaining cellular homeostasis and is essential for the regulation of oxidant stress. Gamma-Glutamyl transferase (GGT) is the first enzyme of the gamma glutamyl cycle that regulates the antioxidant glutathione, hence it is a critical enzyme in glutathione homeostasis. Recent findings have indicated upregulation of GGT in inflammation, increasing antioxidant defence whilst potentially driving leukotriene-induced inflammation. GGT is a marker of future comorbid diseases consistent with inflammation (and oxidative stress) as a key central pathophysiological process. COPD reflects several distinct pathological phenotypes. Inflammation (and hence oxidative stress) is influenced by other factors such as bacterial colonisation and exacerbations. The increased incidence of other co-morbid conditions with systemic inflammation suggests that common pathophysiological processes are responsible. Active oxidant stress and hence the role of GGT may play a role in these processes. Future studies of systemic and local GGT function and genotypes in well characterised patients may lead to a better understanding of the processes involved and hence the development of new treatment strategies.


Effects of Probiotic Bacillus as an Alternative of Antibiotics on Digestive Enzymes Activity and Intestinal Integrity of Piglets.
The previous study in our team found that supplementation of probiotic Bacillus amyloliquefaciens (Ba) instead of antibiotics promote growth performance of piglets. Hence, the present study was carried out to further demonstrate the effect of Ba replacement of antibiotics on digestive and absorption enzyme activity and intestinal microbiota population of piglets. A total of 90 piglets were selected and divided into three groups: G1 group was fed with basal diet supplemented with 150 mg/Kg aureomycin, G2 group was fed with 1 × 108 cfu/Kg Ba and half dose of aureomycin, G3 group was used the diet with 2 × 108cfu/Kg Ba replaced aureomycin. Each treatment had three replications of 10 pigs per pen. Results indicated that Ba replacement significantly increased the activities of amylase, disaccharides and Na+/K+-ATPase. And chymotrypsin activity in different section of intestine was dramatically enhanced in half replacement of aureomycin with Ba. Moreover, Ba replacement maintained the intestinal integrity with the significantly decreased activity of DAO compared with aureomycin group. Besides, supplementation with Ba increased the β-diversity of intestinal microbiota. Taken together, the current study indicated that diet supplementation with Ba instead of aureomycin increased the growth performance of piglets by improving the digestive and absorb enzyme activities, enhancing the intestinal integrity and regulating the population of intestinal micrbiota.


Chloroquine-mediated radiosensitization is due to the destabilization of the lysosomal membrane and subsequent induction of cell death by necrosis.
The anti-malarial drug chloroquine (CQ) is also thought to be a potential radiation sensitizer. To gain a better understanding of how the lysomotropic CQ can potentiate the effects of ionizing radiation, we investigated the effects of CQ on lysosomal and mitochondrial membrane stability, the subcellular localization of ceramide, plasma membrane permeability, and the mode of cell death in response to irradiation. We found that CQ accumulated in the lysosomes and thus lysosomal volumes increased. As a result, both the lysosomal and plasma membranes were destabilized. After 7 Gy irradiation, most ceramide was associated with the lysosomes in the cells treated with CQ but not in the CQ-untreated control. The elevated levels of ceramide in the lysosomes of the CQ-treated cells appeared to further destabilize the lysosomal and plasma membranes of the cell. Both CQ-treated and -untreated cells had approximately the same rate of cell death by apoptosis after 7 Gy irradiation (P > 0.05, ns). However, in contrast to the CQ-untreated control, the CQ-treated cells underwent massive cell death by necrosis at 24-48 h after irradiation (P < 0.05). Taken together, our data support the idea that the increase in cytotoxic effects by the combination of CQ and radiation is due to radiation-mediated apoptosis and CQ-mediated necrosis.


Identification of Key Genes for Hepatitis Delta Virus-Related Hepatocellular Carcinoma by Bioinformatics Analysis.
It has been proposed that hepatitis delta virus (HDV) induces hepatic carcinogenesis by distinct molecular events compared with hepatocellular carcinoma (HCC) that is commonly induced by other hepatitis viruses. This study aimed to explore the underlying mechanism by identifying the key genes for HDV-HCC using bioinformatics analysis. The GSE107170 dataset was downloaded and the differentially expressed genes (DEGs) were obtained by the online tool GEO2R. Gene otology (GO) functional analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using R packages. The protein-protein interaction (PPI) network was constructed by Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Hub genes were selected by Cytoscape software according to degree algorithm. The hub genes were further validated in terms of expression and survival analysis based on public databases. A total of 93 commonly upregulated genes and 36 commonly downregulated genes were found. The top 5 upregulated hub genes were TFRC, ACTR2, ARPC1A, ARPC3, and ARPC2. The top 5 downregulated hub genes were CTNNB1, CCND1, CDKN1B, CDK4, and CDKN1A. In the validation analysis, the expressions of ARPC1A, ARPC3, and CDK4 were promoted in general liver cancer samples. Higher expressions of ARPC2 and CDK4 and lower expressions of CDKN1A, CCND1, and CDKN1B were associated with worse prognosis in general HCC patients. The present study identifies a series of key genes that may be involved in the carcinogenesis of HDV-HCC and used as prognostic factors.


Problematic Use of the Internet and Smartphones in University Students: 2006-2017.
It has been more than a decade since a concern about the addictive use of the Internet and mobile phones was first expressed, and its possible inclusion into the lists of mental disorders has recently become a popular topic of scientific discussion. Thus, it seems to be a fitting moment to investigate the prevalence of this issue over time. The aim of the present study was to analyze the prevalence of the perception of problematic Internet and smartphone use in young people over the period 2006-2017. To this end, a questionnaire on Internet use habits and two questionnaires on the negative consequences of Internet and smartphone use were administered to a sample of 792 university students. The scores were then compared with the results of former studies that had used these questionnaires. The perception of problematic Internet and mobile phone use has increased over the last decade, social networks are considered responsible for this increase, and females are perceived to be more affected than males. The current study shows how strong smartphone and Internet addiction and social media overlap. Participants from 2017 report higher negative consequences of both Internet and mobile phone use than those from 2006, but long-term observations show a decrease in problematic use after a sharp increase in 2013. We conclude that the diagnosis of technological addictions is influenced by both time and social and culture changes.


Stratifying risk of biliary complications in adult living donor liver transplantation by magnetic resonance cholangiography.
Accurate preoperative assessment of biliary anatomy in live donor hepatectomy may be helpful to assess the suitability of a graft and to stratify risk of biliary complications. A retrospective review of existing data among donor and recipients of 36 living donor transplants was performed to assess role of preoperative magnetic resonance cholangiography (MRC) for defining biliary anatomy and to stratify risk of biliary complications. Thirty-six living liver donors underwent MRC, and subsequently right lobectomy. Intraoperative cholangiography and biliary exploration revealed that 24 donors (66.6%) had conventional and 12 (33.3%) had aberrant biliary anatomy. Intraoperative cholangiography demonstrated a strong correlation with MRC (P=0.001) and intraoperative findings (P=0.001). MRC had specificity and positive predictive value of 100%. The risk of developing biliary complication was 5.9 times higher if the biliary anatomy was of any type other than A (P=0.03, CI 1.06-32.9) after controlling for donor age, recipient age, and type of anastomosis. MRC reliably identified variant biliary anatomy. The preoperative MRC demonstrated congruence with the intraoperative cholangiogram and with the intraoperative findings. MRC is helpful in predicting risk of biliary complications in recipients, and identifies donors who would otherwise be excluded intraoperatively by cholangiography, thus limiting the risk of an unnecessary operation.


The gut microbiome in sickle cell disease: Characterization and potential implications.
Sickle Cell Disease (SCD) is an inherited blood disorder that leads to hemolytic anemia, pain, organ damage and early mortality. It is characterized by polymerized deoxygenated hemoglobin, rigid sickle red blood cells and vaso-occlusive crises (VOC). Recurrent hypoxia-reperfusion injury in the gut of SCD patients could increase tissue injury, permeability, and bacterial translocation. In this context, the gut microbiome, a major player in health and disease, might have significant impact. This study sought to characterize the gut microbiome in SCD. Stool and saliva samples were collected from healthy controls (n = 14) and SCD subjects (n = 14). Stool samples were also collected from humanized SCD murine models including Berk, Townes and corresponding control mice. Amplified 16S rDNA was used for bacterial composition analysis using Next Generation Sequencing (NGS). Pairwise group analyses established differential bacterial groups at many taxonomy levels. Bacterial group abundance and differentials were established using DeSeq software. A major dysbiosis was observed in SCD patients. The Firmicutes/Bacteroidetes ratio was lower in these patients. The following bacterial families were more abundant in SCD patients: Acetobacteraceae, Acidaminococcaceae, Candidatus Saccharibacteria, Peptostreptococcaceae, Bifidobacteriaceae, Veillonellaceae, Actinomycetaceae, Clostridiales, Bacteroidacbactereae and Fusobacteriaceae. This dysbiosis translated into 420 different operational taxonomic units (OTUs). Townes SCD mice also displayed gut microbiome dysbiosis as seen in human SCD. A major dysbiosis was observed in SCD patients for bacteria that are known strong pro-inflammatory triggers. The Townes mouse showed dysbiosis as well and might serve as a good model to study gut microbiome modulation and its impact on SCD pathophysiology.


Deciphering the transcriptional regulatory logic of amino acid metabolism.
Although metabolic networks have been reconstructed on a genome scale, the corresponding reconstruction and integration of governing transcriptional regulatory networks has not been fully achieved. Here we reconstruct such an integrated network for amino acid metabolism in Escherichia coli. Analysis of ChIP-chip and gene expression data for the transcription factors ArgR, Lrp and TrpR showed that 19 out of 20 amino acid biosynthetic pathways are either directly or indirectly controlled by these regulators. Classifying the regulated genes into three functional categories of transport, biosynthesis and metabolism leads to the elucidation of regulatory motifs that constitute the integrated network's basic building blocks. The regulatory logic of these motifs was determined on the basis of relationships between transcription factor binding and changes in the amount of transcript in response to exogenous amino acids. Remarkably, the resulting logic shows how amino acids are differentiated as signaling and nutrient molecules, revealing the overarching regulatory principles of the amino acid stimulon.


Trait-mediated interactions: influence of prey size, density and experience.
1. The role of non-consumptive predator effects in structuring ecological communities has become an important area of study for ecologists. Numerous studies have shown that adaptive changes in prey in response to a predator can improve survival in subsequent encounters with that predator. 2. Prey-mediated changes in the shapes of predators' functional response surfaces determine the qualitative predictions of theoretical models. However, few studies have quantified the effects of adaptive prey responses on the shape of predator functional responses. 3. This study explores how prey density, size and previous predator experience interact to change the functional response curves of different-sized predators. 4. We use a response surface design to determine how previous exposure to small or large odonate predators affected the short-term survival of squirrel tree frog (Hyla squirella) tadpoles across a range of sizes and densities (i.e. the shape of odonate functional response curves). 5. Predator-induced tadpoles in a given size class did not differ in shape, although induction changed tadpole behaviour significantly. Induced tadpoles survived better in lethal encounters with either predator than did similar-sized predator-naive tadpoles. 6. Induction by either predator resulted in increased survival with both predators at a given size. However, different mechanisms led to increased survival for induced tadpoles. Attack rate for the small predators, whereas handling time increased for the large predators.


Gallbladder polyps: epidemiology, natural history and management.
Polypoid lesions of the gallbladder affect approximately 5% of the adult population. Most affected individuals are asymptomatic, and their gallbladder polyps are detected during abdominal ultrasonography performed for unrelated conditions. Although the majority of gallbladder polyps are benign, most commonly cholesterol polyps, malignant transformation is a concern. The differentiation of benign from malignant lesions can be challenging. Several features, including patient age, polyp size and number, and rapid growth of polyps, are important discriminating features between benign and malignant polyps. Based on the evidence highlighted in this review, the authors recommend resection in symptomatic patients, as well as in asymptomatic individuals over 50 years of age, or those whose polyps are solitary, greater than 10 mm in diameter, or associated with gallstones or polyp growth on serial ultrasonography. Novel imaging techniques, including endoscopic ultrasonography and enhanced computed tomography, may aid in the differential diagnosis of these lesions and permit expectant management.


Antigen Processing in the Endoplasmic Reticulum Is Monitored by Semi-Invariant αβ TCRs Specific for a Conserved Peptide-Qa-1b MHC Class Ib Ligand.
Ag processing in the endoplasmic reticulum (ER) by the ER aminopeptidase associated with Ag processing (ERAAP) is central to presentation of a normal peptide-MHC class I (MHC I) repertoire. Alternations in ERAAP function cause dramatic changes in the MHC I-presented peptides, which elicit potent immune responses. An unusual subset of CD8+ T cells monitor normal Ag processing by responding to a highly conserved FL9 peptide that is presented by Qa-1b, a nonclassical MHC Ib molecule (QFL) in ERAAP-deficient cells. To understand the structural basis for recognition of the conserved ligand, we analyzed the αβ TCRs of QFL-specific T cells. Individual cells in normal wild-type and TCRβ-transgenic mice were assessed for QFL-specific TCR α- and β-chains. The QFL-specific cells expressed a predominant semi-invariant TCR generated by DNA rearrangement of TRAV9d-3-TRAJ21 α-chain and TRBV5-TRBD1-TRBJ2-7 β-chain gene segments. Furthermore, the CDR3 regions of the α- as well as β-chains were required for QFL ligand recognition. Thus, the αβ TCRs used to recognize the peptide-Qa-1 ligand presented by ERAAP-deficient cells are semi-invariant and likely reflect a conserved mechanism for monitoring the fidelity of Ag processing in the ER.


Quality of life measures in glioma patients with different grades: A preliminary study.
Plethora of information exists in the literature on pathology of the glioma while prevailing research data on quality-of-life (QOL) of glioma patients marks dearth thus demanding more studies. In this study, we examined the QOL of different grades of glioma patients among the Chennai population in India. A total of 162 patients with different grades of glioma enrolled from August 2007 to February 2011, at their first contact to Department of Neurology and Neurosurgery, Government General Hospital, Chennai, India were included and their QOL was assessed by European Organization for Research and Treatment of Cancer Core QOL questionnaire (EORTC QLQc-30), EORTC brain cancer module (QLQ BN-20). Both low and high grade glioma (LGG and HGG) patients had poor mean scores in social functioning (87.0), physical functioning (82.0) and emotional functioning (75.2) and role functioning (58.9). The mean scores on cognitive functioning (61.9) and global QOL (60.3) were better. Age, Karnofsky performance status, World Health Organization grades showed significant associations with all functional scales. The percentage values were higher for symptoms of fatigue (76.9%), pain (71.5%), financial difficulties (77.6%) and appetite loss (38.46%) in both LGG and HGG. Similarly, with respect to QLQ-BN20 domains, HGG patients showed more symptoms than low grade with a significant correlation in communication deficit problems (P = 0.02), headache (P = 0.04), seizures (P < 0.01), hair loss (P < 0.05) than the other symptoms. This initial assessment suggests that an increasing burden of symptoms exists, with poor QOL and survival, which has become a major concern in different grades of glioma patients.


Sleep during the third trimester of pregnancy: the role of depression and anxiety.
Depression has been associated with sleep disturbances in pregnancy; however, no previous research has controlled the possible confounding effect of anxiety on this association. This study aims to analyze the effect of depression on sleep during the third trimester of pregnancy controlling for anxiety. The sample was composed by 143 depressed (n = 77) and non-depressed (n = 66) pregnant women who completed measures of depression, anxiety, and sleep. Differences between groups in sleep controlling for anxiety were found. Depressed pregnant women present higher number of nocturnal awakenings and spent more hours trying falling asleep during the night and the entire 24 h period. Present findings point out the effect of depression on sleep in late pregnancy, after controlling for anxiety.


Biological significance of urolithins, the gut microbial ellagic Acid-derived metabolites: the evidence so far.
The health benefits attributed to pomegranate have been associated with its high content in polyphenols, particularly ellagitannins. This is also the case for other ellagitannin-containing fruits and nuts including strawberry, raspberry, blackberry, walnuts, and muscadine grapes. The bioavailability of ellagitannins and ellagic acid is however very low. These molecules suffer extensive metabolism by the gut microbiota to produce urolithins that are much better absorbed. Urolithins circulate in plasma as glucuronide and sulfate conjugates at concentrations in the range of 0.2-20 μ M. It is therefore conceivable that the health effects of ellagitannin-containing products can be associated with these gut-produced urolithins, and thus the evaluation of the biological effects of these metabolites is essential. Recent research, mostly based on in vitro testing, has shown preliminary evidence of the anti-inflammatory, anticarcinogenic, antiglycative, antioxidant, and antimicrobial effects of urolithins, supporting their potential contribution to the health effects attributed to pomegranate and ellagitannin-rich foods. The number of in vivo studies is still limited, but they show preventive effects of urolithins on gut and systemic inflammation that encourage further research. Both in vivo and mechanistic studies are necessary to clarify the health effects of these metabolites. Attention should be paid when designing these mechanistic studies in order to use the physiologically relevant metabolites (urolithins in gut models and their conjugated derivatives in systemic models) at concentrations that can be reached in vivo.


Longitudinal study of social participation and well-being among persons with spinal cord injury and their partners (pro-WELL).
Social participation is an important determinant of well-being. Among persons with disabilities, and with spinal cord injury (SCI) in particular, opportunities for social participation are restricted and may impact well-being. The longitudinal pro-WELL study aims to investigate associations of 2 major domains of social participation with well-being: (1) availability and quality of close social relationships and (2) acting in core social roles (eg, paid work). The joint inclusion of persons with SCI and their partners is a major innovative aspect of this study enabling an in-depth analysis of interpersonal dynamics in coping with disability. Pro-WELL is a nested project of the Swiss Spinal Cord Injury Cohort Study (SwiSCI) and involves community-dwelling persons aged 30-65 with SCI and their partners living in Switzerland. Baseline data were collected from mid-2015 to early 2016 by telephone interviews and questionnaires. The first and second follow-up assessments are scheduled with a 6 months interval. The baseline sample consists of 133 persons with SCI and their partners. We provide an overview of baseline characteristics and well-being and describe recruitment outcomes and participation rates. A comprehensive non-response analysis demonstrates adequate representation of the source population with negligible selection bias regarding sociodemographic and lesion characteristics. The prospective data collection and analysis of month 6 and 12 assessments are ongoing and tests of the main research hypotheses will be performed. Findings will be disseminated through peer-reviewed journals and scientific conferences. A workshop and a newsletter on study findings are proposed to feed back findings to participants and other stakeholders.


[Postraumatic klüver-Bucy syndrome--description and comparison of two clinical cases].
Klüver-Bucy syndrome was described in the fifties of the 20th century as a group of neuropsychological symptoms, such as visual agnosia, "oral" tendency, hypermetamorphosis, changes in behaviour, hyper-sexuality (homo-, hetero-, autosexuality) and changes in dietary habits (anorexia, bulimia) that may develop in humans after bilateral damage or dysfunction of the medial temporal lobes. The cause of Klüver-Bucy syndrome may be an injury, central nervous system infection, especially herpetic, Pick disease, temporal epilepsy and paraneoplastic encephalopathy. The condition is very rare in children; its occurrence in childhood was described in a few cases only. Symptom intensity and their manifestation depend on numerous diversified factors. A comparative presentation of two clinical cases of Klüver-Bucy syndrome following severe head injuries accompanied by description of computed tomography scans. The diagnosis of the syndrome does not require the presence of all the axial symptoms. Both patients were treated with carbamazepine. Regression of neuropsychological symptoms took a different course in each child, despite their similar brain damage. Fully symptomatic Klüver-Bucy syndrome is very rare. The psychological status of patients with this disorder depends not only on the extent of the lesion, but also on pre-injury emotional and intellectual development and post-injury social stimulation.


Keys to unlock androgen receptor translocation.
The androgen receptor (AR) is tightly linked to prostate cancer, but the mechanisms by which AR transactivation is dysregulated during cancer progression are not fully explored. Dagar et al. examined AR translocation to the nucleus to identify a link between heat shock protein 90 (HSP90) and protein kinase A (PKA). Their findings provide a potential mechanism of the initiation of AR transactivation and potential targets for developing and refining treatments for prostate cancer.


Ultraviolet radiation-induced connective tissue changes in the skin of hairless mice.
Hairless mice (Skh/ hr1 ) were exposed to ultraviolet A (UVA; peak irradiance at 365 nm), or to ultraviolet B (UVB; peak irradiance at 313 nm) radiation. The animals received 12 treatments on alternate days. Connective tissue changes in the skin were monitored by assaying hydroxyproline and desmosine as an indication of collagen and elastin concentrations, respectively. The activities of prolyl hydroxylase and collagen glucosyl-transferase, enzymes participating in the biosynthesis of collagen, were also assayed. The concentration of elastin was significantly increased in mice treated with UVA or UVB. The concentration of collagen was unaffected by the treatments, but the activity of prolyl hydroxylase, reflecting collagen synthetic capacity, was decreased in UVA-treated mice. The collagen glucosyl-transferase activity was unchanged. Irradiation of purified human prolyl hydroxylase with UVA in vitro decreased the enzyme activity at higher doses, but UVB had no effect. The results indicate that definitive changes in the biochemistry of dermal connective tissues can be induced by exposure of mice to UV irradiation.


The association between cognitive impairment and functional outcome in hospitalised older patients: a systematic review and meta-analysis.
in hospitalised older adults, cognitive impairments are common and may be associated with functional outcomes. Our aim was to systematically review this association. we systematically searched MEDLINE, CINAHL, AMED and PsycINFO from inception to April 2016. Non-English language studies were filtered out at search stage. All types of studies were considered for inclusion except reviews, conference abstracts, dissertations and case studies. Population: community-dwelling or institutionalised older adults aged 65 years or more, who are acutely hospitalised and have information on history of dementia and/or cognitive scores on admission. Setting: acute hospital (excluding critical care and subacute or intermediate care). Outcome of interest: change in a measure of physical function or disability between pre-admission or admission, and discharge or post-discharge. This review was registered on PROSPERO (CRD42016035978). the search returned 5,988 unique articles, of which 34 met inclusion criteria. All studies were observational, with 30 prospective and 4 retrospective from 14 countries, recruiting from general medicine (n = 11), geriatric medicine (n = 11) and mixed (n = 12) wards. Twenty-six studies (54,637 participants) were suitable for the quantitative synthesis. The meta-analysis suggested that cognitive impairment was associated with functional decline in hospitalised older adults (risk ratio (RR): 1.64; 95% confidence interval (CI): 1.45-1.86; P < 0.01). Results were similar in subanalyses focusing on diagnosis of dementia (RR: 1.36; 95% CI: 1.05-1.76; P = 0.02; n= 2,248) or delirium (RR: 1.55; 95% CI: 1.31-1.83; P < 0.01; n= 1,677). cognitive impairments seem associated with functional decline in hospitalised older people. Causality cannot be inferred, and limitations include low quality of studies and possible confounding.


Gender differences in preschoolers' help-eliciting communication.
Gender differences in help-eliciting communication and the relationship of such utterances with ability were explored. A sample of 71 preschoolers (38 boys, 33 girls; mean age 4 years 3 months) were videotaped as they solved a difficult puzzle. Spontaneous talk was analyzed for orientation (to whom or to what an utterance referred) and for the frequency of utterances coded as help eliciting. Significant main effects for gender were observed, with more frequent help-eliciting utterances (HEUs) made by the girls than by the boys, particularly HEUs about themselves (self-disclosing). Although the girls' HEUs were not predictive of ability on the puzzle, the boys' were. No gender differences in puzzle-solving ability were observed. Findings are discussed with regard to problem solving and social/linguistic development.


Retronasal perception of odors.
We perceive odors orthonasally during sniffing; in contrast, we perceive odors retronasally during eating when they enter the nose through the pharynx. There are clear differences between orthonasal and retronasal olfaction in neuronal processing and perception, so that these two pathways convey two distinct sensory signals. The perception of foods is based on the interaction between ortho- and retronasal smell, taste, trigeminal activation and texture, so it is difficult to investigate one of these factors in isolation. Specific clinical aspects include effects of retronasal olfaction on satiation and swallowing.


Role of platelet membrane glycoprotein IIb-IIIa in agonist-induced tyrosine phosphorylation of platelet proteins.
Treatment of platelets with thrombin was shown previously to induce rapid changes in tyrosine phosphorylation of several platelet proteins. In this report, we demonstrate that a variety of agonists which induce platelet aggregation also stimulate tyrosine phosphorylation of three proteins with apparent molecular masses of 84, 95, and 97 kD. Since platelet aggregation requires the agonist-induced activation of an integrin receptor (GP IIb-IIIa) as well as the binding of fibrinogen to this receptor, we examined the relationship between tyrosine phosphorylation and the function of GP IIb-IIIa. When platelets were examined under conditions that either precluded the activation of GP IIb-IIIa (prior disruption of the complex by EGTA at 37 degrees C) or the binding of fibrinogen (addition of RGDS or an inhibitory mAb), tyrosine phosphorylation of the 84-, 95-, and 97-kD proteins was not observed. However, although both GP IIb-IIIa activation and fibrinogen binding were necessary for tyrosine phosphorylation, they were not sufficient since phosphorylation was observed only under conditions in which the activated platelets were stirred and allowed to aggregate. In contrast, tyrosine phosphorylation was not dependent on another major platelet response, dense granule secretion. Furthermore, granule secretion did not require tyrosine phosphorylation of this set of proteins. These experiments demonstrate that agonist-induced tyrosine phosphorylation is linked to the process of GP IIb-IIIa-mediated platelet aggregation. Thus, tyrosine phosphorylation may be required for events associated with platelet aggregation or for events that follow aggregation.


STENOTROPHOMONAS MALTOPHILIA ENDOPHTHALMITIS 1 MONTH AFTER INTRAVITREAL AFLIBERCEPT.
Endophthalmitis caused by Stenotrophomonas maltophilia is rare and has been described after cataract surgery and open globe injuries. We report a patient with endophthalmitis caused by this organism after uncomplicated intravitreal aflibercept injection. A 70-year-old man with a history of anti-vascular endothelial growth factor therapy for diabetic macular edema presented 23 days after aflibercept injection with clinical diagnosis of endophthalmitis. The patient initially had mild pain, conjunctival congestion, and anterior chamber cell; 2 days later, the patient returned with hand motion visual acuity, hypopyon, and dense vitritis. A tap and inject procedure was performed. The aqueous sample confirmed the presence of S. maltophilia. Antimicrobial testing showed susceptibility to ceftazidime which was used during the initial treatment. After resolution of the vitritis and hypopyon, the visual acuity returned to 20/70 at his 3-month follow-up examination. Stenotrophomonas maltophilia is a rare infectious agent associated with intravitreal injection and may present 1 month after treatment.


A variant of superficial ulnar artery.
An abnormally superficial course of the ulnar a. in the arm and forearm has long received the attention of anatomists and surgeons. In this study, such a case is reported and its importance from the viewpoint of reconstructive surgery stressed. The most striking findings were the origin of the superficial ulnar a. from the axillary a. and of the common interosseous a. from the radial a.