Personalized medicine in major depressive disorder -- opportunities and pitfalls.

The sequencing of the human genome in the early days of this millennium was greeted with great fanfare as this accomplishment was expected to revolutionize medicine and result in individualized treatments based on the genetic make-up of the patient. The ultimate promise of personalized medicine would be fulfilled with the identification of disease biomarkers that would be widely available for use in diagnosis and treatment. Progress, however, has been slow in providing disease biomarkers or approved diagnostic tests.

Surgical correction of tracheo-oesophageal fistula and oesophageal atresia in infants with VACTERL association: a retrospective case-control study.

Introduction: VACTERL is a rare, non-random association comprising at least three major component features defined by the acronym, and including Vertebral anomalies, Anorectal malformations, Cardiac defects, Tracheo-oEsophageal fistula with or without oesophageal atresia (TOF/OA), Renal abnormalities and Limb anomalies. The aim of this study was to compare the post-operative outcomes following surgical correction of TOF/OA in infants with VACTERL and isolated TOF/OA.

Methods: A retrospective case-control study comparing infants with VACTERL (case group) versus infants with isolated TOF/OA (control group) that underwent surgical correction of TOF/OA at our centre between January 2006 and December 2011.

Brain organochlorines and Lewy pathology: the Honolulu-Asia Aging Study.

Although organochlorines have been reported more frequently in Parkinson's disease (PD) brains than in controls, the association with brain Lewy pathology is unknown. Honolulu-Asia Aging Study (HAAS) participants, exposed to organochlorines from a variety of sources during midlife, represent a population well suited to determining the relationship of brain organochlorines with Lewy pathology in decedents from the longitudinal HAAS. The study design included the measurement of 21 organochlorine levels in frozen occipital lobe samples from HAAS decedents.

Mechanism of protection of transepithelial barrier function by Lactobacillus salivarius: strain dependence and attenuation by bacteriocin production.

Enhanced barrier function is one mechanism whereby commensals and probiotic bacteria limit translocation of foreign antigens or pathogens in the gut. However, barrier protection is not exhibited by all probiotic or commensals and the strain-specific molecules involved remain to be clarified. We evaluated the effects of 33 individual Lactobacillus salivarius strains on the hydrogen peroxide (H(2)O(2))-induced barrier impairment in human epithelial Caco-2 cells.

Psychometric properties of the Strength and Difficulties Questionnaire from five European countries.

The Strength and Difficulties Questionnaire (SDQ) is a brief screening instrument for assessing emotional and behavioural problems in children and adolescents. This study examined the factor structure and validity of the self-report original English version of the SDQ and four of its many translations (German, Cypriot Greek, Swedish, and Italian). A total of 2418 adolescents from five European countries (Germany, Cyprus, England, Sweden, Italy), ages 12 to 17 years, participated.

Chronic exposure to corticosterone enhances the neuroinflammatory and neurotoxic responses to methamphetamine.

Up-regulation of proinflammatory cytokines and chemokines in brain ("neuroinflammation") accompanies neurological disease and neurotoxicity. Previously, we documented a striatal neuroinflammatory response to acute administration of a neurotoxic dose of methamphetamine (METH), i.e.

Alemtuzumab induction therapy in kidney transplantation: a systematic review and meta-analysis.

Background: Alemtuzumab (MabCampath or Campath; Genzyme, Cambridge, MA) is a CD52-specific monoclonal antibody that causes profound and sustained lymphocyte depletion. Its use as an induction therapy in organ transplantation is increasing. Since our last systematic review in 2006, where we identified the need for good-quality randomized controlled trials (RCTs), several RCTs have been published that examine its efficacy and safety in kidney transplantation.

Influence of adhesion and bacteriocin production by Lactobacillus salivarius on the intestinal epithelial cell transcriptional response.

Lactobacillus salivarius strain UCC118 is a human intestinal isolate that has been extensively studied for its potential probiotic effects in human and animal models. The objective of this study was to determine the effect of L. salivarius UCC118 on gene expression responses in the Caco-2 cell line to improve understanding of how the strain might modulate intestinal epithelial cell phenotypes.

Educating surgical patients to reduce the risk of venous thromboembolism: an audit of an effective strategy.

Objectives: Venous thromboembolism (VTE) causes approximately 25,000 deaths each year from hospital-acquired thrombosis in the UK. Patient understanding of risk factors and preventive measures is important in preventing VTE. This audit was designed to assess surgical patient awareness and understanding of VTE risk factors and prophylaxis.

Single mode lasers based on slots suitable for photonic integration.

The re-growth free single mode lasers based on etched slots suitable for photonic integration are presented in this paper. The fabricated 650 μm long laser exhibits a threshold current and a slope efficiency of about 32 mA and 0.12 mW/mA, respectively.

A novel host-responsive sensor mediates virulence and type III secretion during Pseudomonas aeruginosa-host cell interactions.

Sensitive sensory mechanisms are instrumental in affording Pseudomonas aeruginosa the capacity to establish diverse yet severe human infections, which can manifest themselves in long-term untreatable disease. The ability of P. aeruginosa to tightly regulate gene expression and virulence factor production, in response to activation of these sensory components, enables the pathogen to sustain infection despite the host immune response and aggressive antibiotic treatment.

Hydrogel optimization towards fibroblast-friendly biomimetic coatings for implantable devices.

In this paper we present our investigations related to the optimization of hydrogels for the coating/packaging of biomedical devices. In order for hydrogels to be a viable interface/packaging material, a number of conditions must be met. We outline the tailoring of the mechanical properties of a HEMA based hydrogel by exploiting the influence of individual hydrogel components to achieve these requirements.

Preservation solutions for static cold storage of kidney allografts: a systematic review and meta-analysis.

Static cold storage is the most prevalent method for renal allograft preservation. Several solutions have been designed to counteract the detrimental effects of cold ischemia and reperfusion. The aim of this study was to appraise the evidence for the currently available preservation solutions.

Early alterations of brain cellular energy homeostasis in Huntington disease models.

Brain energy deficit has been a suggested cause of Huntington disease (HD), but ATP depletion has not reliably been shown in preclinical models, possibly because of the immediate post-mortem changes in cellular energy metabolism. To examine a potential role of a low energy state in HD, we measured, for the first time in a neurodegenerative model, brain levels of high energy phosphates using microwave fixation, which instantaneously inactivates brain enzymatic activities and preserves in vivo levels of analytes. We studied HD transgenic R6/2 mice at ages 4, 8, and 12 weeks.

Trimethyltin-induced neurotoxicity: gene expression pathway analysis, q-RT-PCR and immunoblotting reveal early effects associated with hippocampal damage and gliosis.

Damage to the CNS results in a complex series of molecular and cellular changes involving the affected targets and the ensuing glial reaction. The initial gene expression events that underlie these cellular responses may serve as early biomarkers of neurotoxicity. Here, we examined gene expression profiles during the initial phase of hippocampal damage resulting from systemic exposure of rats to the organometallic neurotoxicant, trimethyltin (TMT, 8.

Lactobacillus: host-microbe relationships.

Lactobacilli are a subdominant component of the human intestinal microbiota that are also found in other body sites, certain foods, and nutrient-rich niches in the free environment. They represent the types of microorganisms that mammalian immune systems have learned not to react to, which is recognized as a potential driving force in the evolution of the human immune system. Co-evolution of lactobacilli and animals provides a rational basis to postulate an association with health benefits.

Time-dependent slowly-reversible inhibition of monoamine oxidase A by N-substituted 1,2,3,6-tetrahydropyridines.

A novel class of N-substituted tetrahydropyridine derivatives was found to have multiple kinetic mechanisms of monoamine oxidase A inhibition. Eleven structurally similar tetrahydropyridine derivatives were synthesized and evaluated as inhibitors of MAO-A and MAO-B. The most potent MAO-A inhibitor in the series, 2,4-dichlorophenoxypropyl analog 12, displayed time-dependent mixed noncompetitive inhibition.

A Japanese form of social anxiety (taijin kyofusho): frequency and correlates in two generations of the same family.

Background: One specific type of social anxiety, occurring primarily in Japanese culture, is called taijin kyofusho. Taijin kyofusho is characterized by an intense fear that one's body parts or functions displease, embarrass or are offensive to others.

Aim: The main aim of the present study was to compare the frequency and correlates of taijin kyofusho symptoms (TKS) in Japanese adolescents and their parents.

Low oxygen induces the type III secretion system in Pseudomonas aeruginosa via modulation of the small RNAs rsmZ and rsmY.

A steep oxygen gradient within the mucus of the cystic fibrosis (CF) lung combined with the biofilm mode of bacterial growth forces respiratory pathogens to adapt to varying oxygen availability. This study presents the novel finding that the Pseudomonas aeruginosa response to limiting oxygen stress includes induction of its type III secretion system (T3SS), which subsequently contributes towards host cell cytotoxicity. In P.

Organophosphates dysregulate dopamine signaling, glutamatergic neurotransmission, and induce neuronal injury markers in striatum.

The neurological effects of organophosphate (OP) pesticides, commonly used on foods and in households, are an important public health concern. Furthermore, subclinical exposure to combinations of organophosphates is implicated in Gulf War illness. Here, we characterized the effects of the broadly used insecticide chlorpyrifos (CPF) on dopamine and glutamatergic neurotransmission effectors in corticostriatal motor/reward circuitry.

Recommendations for patient selection in spinal cord stimulation.

Studies have shown that spinal cord stimulation (SCS) can reduce chronic pain by at least 50% over prolonged periods, improve function and quality-of-life, reduce requirements for healthcare resources and enable return to work in appropriately selected patients. However, SCS does not provide pain relief in all patients and is an expensive, labor intensive and invasive procedure with complications and ongoing management that requires specialists with specific skills and judgment. Multidisciplinary selection of appropriate patients for SCS is essential to achieve maximal benefit from the procedure.

Gestational lead exposure selectively decreases retinal dopamine amacrine cells and dopamine content in adult mice.

Gestational lead exposure (GLE) produces supernormal scotopic electroretinograms (ERG) in children, monkeys and rats, and a novel retinal phenotype characterized by an increased number of rod photoreceptors and bipolar cells in adult mice and rats. Since the loss of dopaminergic amacrine cells (DA ACs) in GLE monkeys and rats contributes to supernormal ERGs, the retinal DA system was analyzed in mice following GLE. C57BL/6 female mice were exposed to low (27 ppm), moderate (55 ppm) or high (109 ppm) lead throughout gestation and until postnatal day 10 (PN10).

Effects of repeated treatment with phosphodiesterase-4 inhibitors on cAMP signaling, hippocampal cell proliferation, and behavior in the forced-swim test.

The effects of repeated treatment with the phosphodiesterase-4 (PDE4) inhibitors rolipram, piclamilast, and 4-(2-(3-(cyclopentyloxy)-4-methoxyphenyl)-2-phenylethyl)pyridine (CDP840), which differ in their interactions with high- and low-affinity binding conformers of the enzyme, were contrasted to those of acute treatment on cAMP signaling, hippocampal cell proliferation, and immobility in the forced-swim test in rats. Repeated treatment with rolipram (1 and 3 mg/kg), piclamilast (0.3 and 1 mg/kg), or CDP840 (10 and 30 mg/kg) for 16 days increased cAMP and phosphorylation of cAMP response element binding protein (pCREB) in hippocampus and prefrontal cortex.

Anxiety symptoms among adolescents in Japan and England: their relationship with self-construals and social support.

Background: Most of our knowledge about anxiety in adolescents has come from studies conducted in Western countries. Little is known about the extent to which these results can be generalized to those who live in other cultures. The main aim of this study was to compare the frequency and correlates of anxiety symptoms among adolescents in Japan and England.