1-(2-Hydr­oxy-5-methyl­phen­yl)-3-(3-methylthiophen-2-yl)prop-2-en-1-one

In the structure of the title compound, C15H14O2S, the benzene ring is nearly coplanar with the thio­phene ring. The hydroxy group substituted at C2 position is in an antiperi­planar conformation with respect to the phenyl ring. The crystal structure exhibits weak intramolecular O—H⋯O hydrogen bonding

Identification of genes important for cutaneous function revealed by a large scale reverse genetic screen in the mouse.

The skin is a highly regenerative organ which plays critical roles in protecting the body and sensing its environment. Consequently, morbidity and mortality associated with skin defects represent a significant health issue. To identify genes important in skin development and homeostasis, we have applied a high throughput, multi-parameter phenotype screen to the conditional targeted mutant mice generated by the Wellcome Trust Sanger Institute's Mouse Genetics Project (Sanger-MGP). A total of 562 different mouse lines were subjected to a variety of tests assessing cutaneous expression, macroscopic clinical disease, histological change, hair follicle cycling, and aberrant marker expression. Cutaneous lesions were associated with mutations in 23 different genes. Many of these were not previously associated with skin disease in the organ (Mysm1, Vangl1, Trpc4ap, Nom1, Sparc, Farp2, and Prkab1), while others were ascribed new cutaneous functions on the basis of the screening approach (Krt76, Lrig1, Myo5a, Nsun2, and Nf1). The integration of these skin specific screening protocols into the Sanger-MGP primary phenotyping pipelines marks the largest reported reverse genetic screen undertaken in any organ and defines approaches to maximise the productivity of future projects of this nature, while flagging genes for further characterisation

PACAP-38 induces neuronal differentiation of human SH-SY5Y neuroblastoma cells via cAMP-mediated activation of ERK and p38 MAP kinases1

The intracellular signaling pathways mediating the neurotrophic actions of pituitary adenylate cyclase-activating polypeptide (PACAP) were investigated in human neuroblastoma SH-SY5Y cells. Previously, we showed that SH-SY5Y cells express the PAC1 and VIP/PACAP receptor type 2 (VPAC2) receptors, and that the robust cAMP production in response to PACAP and vasoactive intestinal peptide (VIP) was mediated by PAC1 receptors (Lutz et al. 2006). Here, we investigated the ability of PACAP-38 to differentiate SH-SY5Y cells by measuring morphological changes and the expression of neuronal markers. PACAP-38 caused a concentration-dependent increase in the number of neurite-bearing cells and an up-regulation in the expression of the neuronal proteins Bcl-2, growth-associated protein-43 (GAP-43) and choline acetyltransferase: VIP was less effective than PACAP-38 and the VPAC2 receptor-specific agonist, Ro 25-1553, had no effect. The effects of PACAP-38 and VIP were blocked by the PAC1 receptor antagonist, PACAP6-38. As observed with PACAP-38, the adenylyl cyclase activator, forskolin, also induced an increase in the number of neurite-bearing cells and an up-regulation in the expression of Bcl-2 and GAP-43. PACAP-induced differentiation was prevented by the adenylyl cyclase inhibitor, 2′,5′-dideoxyadenosine (DDA), but not the protein kinase A (PKA) inhibitor, H89, or by siRNA-mediated knock-down of the PKA catalytic subunit. PACAP-38 and forskolin stimulated the activation of extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MAP; p38 MAP kinase) and c-Jun N-terminal kinase (JNK). PACAP-induced neuritogenesis was blocked by the MEK1 inhibitor PD98059 and partially by the p38 MAP kinase inhibitor SB203580. Activation of exchange protein directly activated by cAMP (Epac) partially mimicked the effects of PACAP-38, and led to the phosphorylation of ERK but not p38 MAP kinase. These results provide evidence that the neurotrophic effects of PACAP-38 on human SH-SY5Y neuroblastoma cells are mediated by the PAC1 receptor through a cAMP-dependent but PKA-independent mechanism, and furthermore suggest that this involves Epac-dependent activation of ERK as well as activation of the p38 MAP kinase signaling pathway

The impact of xerostomia on oral-health-related quality of life among younger adults

BACKGROUND: Recent research has suggested that chronic dry mouth affects the day-to-day lives of older people living in institutions. The condition has usually been considered to be a feature of old age, but recent work by our team produced the somewhat surprising finding that 10% of people in their early thirties are affected. This raises the issue of whether dry mouth is a trivial condition or a more substantial threat to quality of life among younger people. The objective of this study was to examine the association between xerostomia and oral-health-related quality of life among young adults while controlling for clinical oral health status and other potential confounding factors. METHODS: Cross-sectional analysis of data from a longstanding prospective observational study of a Dunedin (New Zealand) birth cohort: clinical dental examinations and questionnaires were used at age 32. The main measures were xerostomia (the subjective feeling of dry mouth, measured with a single question) and oral-health-related quality of life (OHRQoL) measured using the short-form Oral Health Impact Profile (OHIP-14). RESULTS: Of the 923 participants (48.9% female), one in ten were categorised as 'xerostomic', with no apparent gender difference. There was a strong association between xerostomia and OHRQoL (across all OHIP-14 domains) which persisted after multivariate analysis to control for clinical characteristics, gender, smoking status and personality characteristics (negative emotionality and positive emotionality). CONCLUSION: Xerostomia is not a trivial condition; it appears to have marked and consistent effects on sufferers' day-to-day lives

Targeting of Slc25a21 is associated with orofacial defects and otitis media due to disrupted expression of a neighbouring gene.

Homozygosity for Slc25a21(tm1a(KOMP)Wtsi) results in mice exhibiting orofacial abnormalities, alterations in carpal and rugae structures, hearing impairment and inflammation in the middle ear. In humans it has been hypothesised that the 2-oxoadipate mitochondrial carrier coded by SLC25A21 may be involved in the disease 2-oxoadipate acidaemia. Unexpectedly, no 2-oxoadipate acidaemia-like symptoms were observed in animals homozygous for Slc25a21(tm1a(KOMP)Wtsi) despite confirmation that this allele reduces Slc25a21 expression by 71.3%. To study the complete knockout, an allelic series was generated using the loxP and FRT sites typical of a Knockout Mouse Project allele. After removal of the critical exon and neomycin selection cassette, Slc25a21 knockout mice homozygous for the Slc25a21(tm1b(KOMP)Wtsi) and Slc25a21(tm1d(KOMP)Wtsi) alleles were phenotypically indistinguishable from wild-type. This led us to explore the genomic environment of Slc25a21 and to discover that expression of Pax9, located 3' of the target gene, was reduced in homozygous Slc25a21(tm1a(KOMP)Wtsi) mice. We hypothesize that the presence of the selection cassette is the cause of the down regulation of Pax9 observed. The phenotypes we observed in homozygous Slc25a21(tm1a(KOMP)Wtsi) mice were broadly consistent with a hypomorphic Pax9 allele with the exception of otitis media and hearing impairment which may be a novel consequence of Pax9 down regulation. We explore the ramifications associated with this particular targeted mutation and emphasise the need to interpret phenotypes taking into consideration all potential underlying genetic mechanisms

The relationship between childhood body weight and dental caries experience:an umbrella systematic review protocol

Abstract Background Obesity and dental caries are global public health problems which can impact in childhood and throughout the life course. In simple terms, childhood dental caries and body weight are linked via the common risk factor of diet. An association between dental caries and obesity has been described in a number of studies and reviews. However, similarly, a relationship has also been noted between low body weight and caries experience in children. This protocol will provide the framework for an umbrella review to address the following question: Does the available evidence support a relationship between dental caries experience and body weight in the child population? Methods This review protocol outlines the process to carry out an umbrella systematic review which will synthesise previous reviews of childhood dental caries experience and body weight. An umbrella review methodology will be used to examine the methodological and reporting quality of existing reviews. Discussion The final umbrella review aims to aggregate the available evidence in order to provide a summary for policymakers and to inform healthcare interventions. Systematic review registration PROSPERO CRD4201604730

Fear causes tears - Perineal injuries in home birth settings. A Swedish interview study

<p>Abstract</p> <p>Background</p> <p>Perineal injury is a serious complication of vaginal delivery that has a severe impact on the quality of life of healthy women. The prevalence of perineal injuries among women who give birth in hospital has increased over the last decade, while it is lower among women who give birth at home. The aim of this study was to describe the practice of midwives in home birth settings with the focus on the occurrence of perineal injuries.</p> <p>Methods</p> <p>Twenty midwives who had assisted home births for between one and 29 years were interviewed using an interview guide. The midwives also had experience of working in a hospital delivery ward. All the interviews were tape-recorded and transcribed. Content analysis was used.</p> <p>Results</p> <p>The overall theme was "No rushing and tearing about", describing the midwives' focus on the natural process taking its time. The subcategories 1) preparing for the birth; 2) going along with the physiological process; 3) creating a sense of security; 4) the critical moment and 5) midwifery skills illuminate the management of labor as experienced by the midwives when assisting births at home.</p> <p>Conclusions</p> <p>Midwives who assist women who give birth at home take many things into account in order to minimize the risk of complications during birth. Protection of the woman's perineum is an act of awareness that is not limited to the actual moment of the pushing phase but starts earlier, along with the communication between the midwife and the woman.</p

The role of melatonin in the pathogenesis of adolescent idiopathic scoliosis (AIS)

The cause of adolescent idiopathic scoliosis (AIS) in humans remains obscure and probably multifactorial. At present, there is no proven method or test available to identify children or adolescent at risk of developing AIS or identify which of the affected individuals are at risk of progression. Reported associations are linked in pathogenesis rather than etiologic factors. Melatonin may play a role in the pathogenesis of scoliosis (neuroendocrine hypothesis), but at present, the data available cannot clearly show the role of melatonin in producing scoliosis in humans. The data regarding human melatonin levels are mixed at best, and the melatonin deficiency as a causative factor in the etiology of scoliosis cannot be supported. It will be an important issue of future research to investigate the role of melatonin in human biology, the clinical efficacy, and safety of melatonin under different pathological situations. Research is needed to better define the role of all factors in AIS development