Reinventing Nuclear Histo-score Utilizing Inherent Morphologic Cutoffs: Blue-brown Color H-score (BBC-HS).

Immunohistochemistry (IHC) is a testing methodology that is widely used for large number of diagnostic, prognostic, and predictive biomarkers. Although IHC is a qualitative methodology, in addition to threshold-based stratification (positive vs. negative), the increasing levels of expression of some of these biomarkers often lead to more intense staining, which published evidence linked to specific diagnosis, prognosis, and responses to therapy.

The Association of Placental Abruption and Pediatric Neurological Outcome: A Systematic Review and Meta-Analysis.

Placental histopathology provides insights, or "snapshots", into relevant antenatal factors that could elevate the risk of perinatal brain injury. We present a systematic review and meta-analysis comparing frequencies of adverse neurological outcomes in infants born to women with placental abruption versus without abruption. Records were sourced from MEDLINE, Embase, and the CENTRAL Trials Registry from 1946 to December 2019.

Apparent Homozygosity for a gr/gr AZFc Deletion in A 47,XYY Man with Oligozoospermia and Secondary Infertility.

Background: Approximately 1 in 1000 men have a 47,XYY karyotype. Previous publications have presented cases of infertile XYY men and have suggested that the additional Y chromosome may cause disrupted meiosis leading to sperm apoptosis. The purpose of the current study was to determine whether XYY men are over-represented in infertility cohorts.

Identifying susceptibility genes for primary ovarian insufficiency on the high-risk genetic background of a fragile X premutation.

Objective: To identify modifying genes that explains the risk of fragile X-associated primary ovarian insufficiency (FXPOI).

Design: Gene-based, case/control association study, followed by a functional screen of highly ranked genes using a Drosophila model.

Setting: Participants were recruited from academic and clinical settings.

Biorelevant and screening dissolution methods for minocycline hydrochloride microspheres intended for periodontal administration.

Currently, there is no compendial-level method to assess dissolution of particulate systems administered in the periodontal pocket. This work seeks to develop dissolution methods for extended release poly(lactic-co-glycolic acid) (PLGA) microspheres applied in the periodontal pocket. Arestin®, PLGA microspheres containing minocycline hydrochloride (MIN), is indicated for reduction of pocket depth in adult periodontitis.

Expansions and contractions of the FMR1 CGG repeat in 5,508 transmissions of normal, intermediate, and premutation alleles.

Instability of the FMR1 repeat, commonly observed in transmissions of premutation alleles (55-200 repeats), is influenced by the size of the repeat, its internal structure and the sex of the transmitting parent. We assessed these three factors in unstable transmissions of 14/3,335 normal (~5 to 44 repeats), 54/293 intermediate (45-54 repeats), and 1561/1,880 premutation alleles. While most unstable transmissions led to expansions, contractions to smaller repeats were observed in all size classes.

Report of a workshop on ensuring sustainable access to safe blood in developing countries: International Blood Safety Forum, March 24, 2017.

On March 24, 2017, more than 90 experts in blood safety and international development from blood centers, industry, government, and international and nongovernmental organizations gathered in Arlington, Virginia, for the Third International Blood Safety Forum, cosponsored by America's Blood Centers and Global Healing. This report summarizes presentations and major conclusions. The meeting explored ways to increase access to affordable, safe blood for low- and lower-middle-income countries (LMICs) in an era when funding from the US President's Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund has been redirected from preventing the spread of human immunodeficiency virus (HIV) to diagnosing and treating the 25 million-plus people living with HIV in LMICs.

Investigating Ebola virus pathogenicity using molecular dynamics.

Background: Ebolaviruses have been known to cause deadly disease in humans for 40 years and have recently been demonstrated in West Africa to be able to cause large outbreaks. Four Ebolavirus species cause severe disease associated with high mortality in humans. Reston viruses are the only Ebolaviruses that do not cause disease in humans.

Development of Genetic Testing for Fragile X Syndrome and Associated Disorders, and Estimates of the Prevalence of FMR1 Expansion Mutations.

The identification of a trinucleotide (CGG) expansion as the chief mechanism of mutation in Fragile X syndrome in 1991 heralded a new chapter in molecular diagnostic genetics and generated a new perspective on mutational mechanisms in human genetic disease, which rapidly became a central paradigm ("dynamic mutation") as more and more of the common hereditary neurodevelopmental disorders were ascribed to this novel class of mutation. The progressive expansion of a CGG repeat in the gene from "premutation" to "full mutation" provided an explanation for the "Sherman paradox," just as similar expansion mechanisms in other genes explained the phenomenon of "anticipation" in their pathogenesis. Later, premutations were unexpectedly found associated with two other distinct phenotypes: primary ovarian insufficiency and tremor-ataxia syndrome.

Multiplex families with epilepsy: Success of clinical and molecular genetic characterization.

Objective: To analyze the clinical syndromes and inheritance patterns of multiplex families with epilepsy toward the ultimate aim of uncovering the underlying molecular genetic basis.

Methods: Following the referral of families with 2 or more relatives with epilepsy, individuals were classified into epilepsy syndromes. Families were classified into syndromes where at least 2 family members had a specific diagnosis.

Population-based estimates of the prevalence of FMR1 expansion mutations in women with early menopause and primary ovarian insufficiency.

Purpose: Primary ovarian insufficiency before the age of 40 years affects 1% of the female population and is characterized by permanent cessation of menstruation. Genetic causes include FMR1 expansion mutations. Previous studies have estimated mutation prevalence in clinical referrals for primary ovarian insufficiency, but these are likely to be biased as compared with cases in the general population.

Spontaneous hemorrhagic Descemet membrane detachment causing pupillary block.

Purpose: To present a unique case of a 65-year-old man using warfarin who presented with acute unilateral loss of vision due to hemorrhagic Descemet membrane detachment (DMD) with pupillary block and elevated intraocular pressure and its subsequent treatment and challenges.

Method: Case report.

Results: Clinical examination showed a visual acuity of finger counting, central DMD with near contact to the iris and premembrane hemorrhage, an intraocular pressure (IOP) of 19 mmHg, and normal pupillary reaction.

New neuropathological findings in Unverricht-Lundborg disease: neuronal intranuclear and cytoplasmic inclusions.

Unverricht-Lundborg disease (EPM1A), also known as Baltic myoclonus, is the most common form of progressive myoclonic epilepsy. It is inherited as an autosomal recessive trait, due to mutations in the Cystatin-B gene promoter region. Although there is much work on rodent models of this disease, there is very little published neuropathology in patients with EPM1A.

Intermediate sized CGG repeats are not a common cause of idiopathic premature ovarian failure.

Background: It is recognized that FMR1 premutation expansions are associated with premature ovarian failure (POF), but the role of smaller repeats at the boundary of premutation and normal is less clear.

Methods: We have therefore investigated the incidence of these intermediate sized FMR1 CGG repeats (35-58 repeats) in a series of 366 women ascertained because of menopause before the age of 40.

Results: We found no significant difference in the incidence of intermediates in cases compared with controls.

Fragile XE: an important differential diagnosis.

Fragile X is a common cause of mental retardation in boys that can also affect girls. We present the case of a 21-year-old woman with Fragile X E (FRAXE) with learning difficulty, behavioural problems and epilepsy. Her diagnosis was made after investigations spanning several years, highlighting the importance of considering FRAXE and the benefits of reviewing genetic test results in the light of advancing technology.

Safety, risk acceptability, and morality.

The primary aim of this article is to develop and defend a conceptual analysis of safety. The article begins by considering two previous analyses of safety in terms of risk acceptability. It is argued that these analyses fail because the notion of risk acceptability is more subjective than safety, as risk acceptability takes into account potential benefits in a way that safety does not.

The development of a quality assessment tool for ambulance patient care records.

A retrospective cohort study of the 2002 Victorian prehospital emergency care documentation completed by ambulance paramedics had the objectives: (i) to design and implement a quality assessment tool to determine the quality of the ambulance patient care record (PCR)information; and (ii) to identify critical demographic and clinical items on the ambulance PCR that needed improvement. The study outcomes included a functioning quality assessment tool and associated user guide for prehospital use, and the identification of three critical PCR components requiring improvement. Ninety percent of PCRs passed the quality assessment; 10% (approximately 5 300) contained measurably poor or incomplete documentation.

Observation of an excess of fragile-X premutations in a population of males referred with spinocerebellar ataxia.

Premutations of the fragile-X (FRAXA) gene were thought to have no clinical effects until recent reports of an increased incidence of premature ovarian failure in females and a late-onset neurological disorder in males. These patients were identified from families including typical fragile-X males with a full mutation. By analysing a cohort of patients with neurodegenerative disorders referred for genetic analysis of spinocerebellar ataxia genes, we have found that 3 of 59 males carry the premutation.

Expansion of the fragile X CGG repeat in females with premutation or intermediate alleles.

The CGG repeat in the 5' untranslated region of the fragile X mental retardation 1 gene (FMR1) exhibits remarkable instability upon transmission from mothers with premutation alleles. A collaboration of 13 laboratories in eight countries was established to examine four issues concerning FMR1 CGG-repeat instability among females with premutation (approximately 55-200 repeats) and intermediate (approximately 46-60 repeats) alleles. Our central findings were as follows: (1) The smallest premutation alleles that expanded to a full mutation (>200 repeats) in one generation contained 59 repeats; sequence analysis of the 59-repeat alleles from these two females revealed no AGG interruptions within the FMR1 CGG repeat.