Plasma p-tau217 predicts cognitive impairments up to ten years before onset in normal older adults.

Importance: Positron emission tomography (PET) biomarkers are the gold standard for detection of Alzheimer amyloid and tau . Such imaging can identify cognitively unimpaired (CU) individuals who will subsequently develop cognitive impartment (CI). Plasma biomarkers would be more practical than PET or even cerebrospinal fluid (CSF) assays in clinical settings.

A systematic review of the potential consequences of abnormal serum levels of vitamin B6 in people living with Parkinson's disease.

The prevalences of polyneuropathy and epilepsy are higher in people living with Parkinson's disease (PwPD) when compared to older adults. Vitamin B6 is widely available and affordable. PwPD are at higher risk of having abnormal serum levels of vitamin B6, which are associated with polyneuropathy and epilepsy that are potentially preventable and treatable.

From design to action: participatory approach to capacity building needs for local overdose response plans.

Background: In response to the rise in opioid-related deaths, communities across Ontario have developed opioid or overdose response plans to address issues at the local level. Public Health Ontario (PHO) leads the Community Opioid / Overdose Capacity Building (COM-CAP) project, which aims to reduce overdose-related harms at the community level by working with communities to identify, develop, and evaluate capacity building supports for local needs around overdose planning. The 'From Design to Action' co-design workshop used a participatory design approach to engage communities in identifying the requirements for capacity building support.

Web-Based Co-design in Health Care: Considerations for Renewed Participation.

The COVID-19 pandemic has shifted the work environment to a new reality of remote work and virtual collaboration. This shift has occurred in various work settings with an impact on spaces, approaches, applied techniques, and tools. This has resulted in the broad use of virtual tools in the health care sector to avoid physical encounters and in-person interactions that will likely outlast the COVID-19 pandemic.

Live births in women with recurrent hydatidiform mole and two NLRP7 mutations.

Hydatidiform mole (HM) is an aberrant human pregnancy with abnormal embryonic development and excessive proliferation of the trophoblast. Recessive mutations in NLRP7 are responsible for recurrent HM (RHM). Women with recessive NLRP7 mutations fail to have normal pregnancies from spontaneous conceptions with the exception of three out of 131 reported patients.

Comprehensive genotype-phenotype correlations between NLRP7 mutations and the balance between embryonic tissue differentiation and trophoblastic proliferation.

Background: Hydatidiform mole (HM) is a human pregnancy with excessive trophoblastic proliferation and abnormal embryonic development that may be sporadic or recurrent. In the sporadic form, the HM phenotype is driven by an abnormal ratio of paternal to maternal genomes, whereas in the recurrent form, the HM phenotype is caused by maternal-recessive mutations, mostly in NLRP7, despite the diploid biparental origin of the HM tissues. In this study, we characterised the expression of the imprinted, maternally expressed gene, CDKN1C (p57(KIP2)), the genotype, and the histopathology of 36 products of conception (POC) from patients with two defective alleles in NLRP7 and looked for potential correlations between the nature of the mutations in the patients and the various HM features.

Suggestion overrides automatic audiovisual integration.

Cognitive scientists routinely distinguish between controlled and automatic mental processes. Through learning, practice, and exposure, controlled processes can become automatic; however, whether automatic processes can become deautomatized - recuperated under the purview of control - remains unclear. Here we show that a suggestion derails a deeply ingrained process involving involuntary audiovisual integration.

Absence of KHDC3L mutations in Chinese patients with recurrent and sporadic hydatidiform moles.

To date, two maternal-effect genes have been shown to play causal roles in recurrent hydatidiform moles (RHMs). NLRP7, a major gene for this condition, codes for a nucleotide-binding oligomerization domain-like receptor and is mutated in 48 to 60% of patients with RHMs. KHDC3L is a recently identified gene that is mutated in 14% of NLRP7-negative patients.

Report of four new patients with protein-truncating mutations in C6orf221/KHDC3L and colocalization with NLRP7.

To date, two maternal-effect genes have been shown to have causative roles in recurrent hydatidiform moles (RHMs); NLRP7 that is mutated in 48-60% of patients with RHMs and C6orf221 (HUGO-approved nomenclature is now KHDC3L), a recently identified gene, that is mutated in 14% of patients with RHMs who are negative for NLRP7 mutations. We sequenced KHDC3L in 97 patients with RHMs and reproductive loss who are mostly negative for NLRP7 mutations. We identified three unrelated patients, each homozygous for one of the two protein-truncating mutations, a novel 4-bp deletion resulting in a frameshift, c.

Placebos in clinical practice: comparing attitudes, beliefs, and patterns of use between academic psychiatrists and nonpsychiatrists.

Controversial and ethically tenuous, the use of placebos is central to medicine but even more pivotal to psychosocial therapies. Scholars, researchers, and practitioners largely disagree about the conceptualization of placebos. While different professionals often confound the meanings of placebo effects with placebo responses, physicians continue to prescribe placebos as part of clinical practice.

Comparative ICE genomics: insights into the evolution of the SXT/R391 family of ICEs.

Integrating and conjugative elements (ICEs) are one of the three principal types of self-transmissible mobile genetic elements in bacteria. ICEs, like plasmids, transfer via conjugation; but unlike plasmids and similar to many phages, these elements integrate into and replicate along with the host chromosome. Members of the SXT/R391 family of ICEs have been isolated from several species of gram-negative bacteria, including Vibrio cholerae, the cause of cholera, where they have been important vectors for disseminating genes conferring resistance to antibiotics.

Clinical and molecular phenotype of Aicardi-Goutieres syndrome.

Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3'-->5' exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease.

Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutières syndrome and mimic congenital viral brain infection.

Aicardi-Goutières syndrome (AGS) is an autosomal recessive neurological disorder, the clinical and immunological features of which parallel those of congenital viral infection. Here we define the composition of the human ribonuclease H2 enzyme complex and show that AGS can result from mutations in the genes encoding any one of its three subunits. Our findings demonstrate a role for ribonuclease H in human neurological disease and suggest an unanticipated relationship between ribonuclease H2 and the antiviral immune response that warrants further investigation.

Antagonistic properties of two recombinant strains of Streptomyces melanosporofaciens obtained by intraspecific protoplast fusion.

Intraspecific protoplast fusion was used to produce stable prototrophic recombinants of Streptomyces melanosporofaciens EF-76, a biocontrol agent of plant disease producing geldanamycin. Two recombinant strains (FP-54 and FP-60) that differed with regard to their antagonistic properties against Bacillus cereus ATCC 14579, Streptomyces scabies EF-35 and Phytophthora fragariae var. rubi 390 were characterized.

Characterization of bifidobacteria by random DNA amplification.

RAPD conditions were optimized to generate reproducible banding patterns by testing primers, thermocyclers and overall reproducibility in repeat DNA analysis and separate DNA extractions. Five primers were chosen on the basis of band intensity and distribution (between 2 and 10 bands) which clearly distinguished among strains of Bifidobacterium adolescentis, B. animalis, B.

Glucanolytic Actinomycetes Antagonistic to Phytophthora fragariae var. rubi, the Causal Agent of Raspberry Root Rot.

A collection of about 200 actinomycete strains was screened for the ability to grow on fragmented Phytophthora mycelium and to produce metabolites that inhibit Phytophthora growth. Thirteen strains were selected, and all produced (beta)-1,3-, (beta)-1,4-, and (beta)-1,6-glucanases. These enzymes could hydrolyze glucans from Phytophthora cell walls and cause lysis of Phytophthora cells.

Saccharopolyspora hirsuta 367 encodes clustered genes similar to ketoacyl synthase, ketoacyl reductase, acyl carrier protein, and biotin carboxyl carrier protein.

The actI gene, encoding a component of the actinorhodin polyketide synthase of Streptomyces coelicolor, was used to identify and clone a homologous 11.7 kb BamHI DNA fragment from Saccharopolyspora hirsuta 367. The cloned fragment complemented actinorhodin production in a strain of Streptomyces coelicolor bearing a mutant actI gene.

A cloned replicon of Saccharopolyspora phages JHJ-1 and JHJ-3 is stably maintained as a plasmid in various actinomycetes.

A replicon of phage JHJ-1 (and JHJ-3) was cloned. The autonomously replicating phage element was maintained as a medium-copy-number shuttle plasmid in many actinomycetes, and was efficiently transmitted to spores without antibiotic selection. One gene was shown to be expressed in a vector containing the JHJ-3 replicon.

Construction of a shuttle lacZ alpha-based Escherichia coli-actinomycetes vector containing the phage JHJ-3 replicon.

Using the broad replicating range JHJ-3 phage replicon, a shuttle vector for Escherichia coli and actinomycetes has been constructed. The vector, pOJ31, bears the lacZ alpha fragment allowing a blue/white gene cloning system. pOJ31 also contains a polylinker of 15 unique cloning sites and the phage T7 promoter.

Biological characterization of induced phages from Saccharopolyspora hirsuta 367 and comparison with phage JHJ-1.

Phages JHJ-2 and JHJ-3 were isolated from Saccharopolyspora hirsuta 367 UC 8106 following induction with mitomycin C and amplified on S. hirsuta NRRL B-5792. Their properties were compared with those of phage JHJ-1, isolated previously from S.

Doppler umbilical artery velocimetry in fetuses with polyhydramnios.

Polyhydramnios is a condition of multiple etiologies, many of a benign nature, but some of which are incompatible with life. To evaluate Doppler velocimetry results as a prognostic parameter in these fetuses, we reviewed all of our cases of polyhydramnios that underwent Doppler analysis in the third trimester. Fifty-four fetuses were studied.

Amniotic fluid index: an appropriate predictor of perinatal outcome.

Qualitative amniotic fluid volume determination is a routine part of the fetal biophysical profile score. Quantitative amniotic fluid volume measurement, however, is not a factor in the determination of the standard biophysical profile score. This study is a retrospective analysis of antepartum assessment of amniotic fluid volumes and their relationship to neonatal outcomes.