Experimental evidence for temporal uncoupling of brain Aβ deposition and neurodegenerative sequelae.

Brain Aβ deposition is a key early event in the pathogenesis of Alzheimer´s disease (AD), but the long presymptomatic phase and poor correlation between Aβ deposition and clinical symptoms remain puzzling. To elucidate the dependency of downstream pathologies on Aβ, we analyzed the trajectories of cerebral Aβ accumulation, Aβ seeding activity, and neurofilament light chain (NfL) in the CSF (a biomarker of neurodegeneration) in Aβ-precursor protein transgenic mice. We find that Aβ deposition increases linearly until it reaches an apparent plateau at a late age, while Aβ seeding activity increases more rapidly and reaches a plateau earlier, coinciding with the onset of a robust increase of CSF NfL.

Analysis of the Understanding and Worry about Lymphedema of Patients with Breast Cancer.

Background: Lymphedema is a potential lifelong sequela of breast cancer treatment. We sought to: (1) evaluate the worry and knowledge of patients about lymphedema, (2) quantify patients reporting lymphedema education and screening, and (3) determine willingness to participate in lymphedema screening and prevention programs.

Patients And Methods: A survey evaluating lymphedema-related knowledge and worry was sent to patients treated for stage 0-III breast cancer.

Acute targeting of pre-amyloid seeds in transgenic mice reduces Alzheimer-like pathology later in life.

Amyloid-β (Aβ) deposits are a relatively late consequence of Aβ aggregation in Alzheimer's disease. When pathogenic Aβ seeds begin to form, propagate and spread is not known, nor are they biochemically defined. We tested various antibodies for their ability to neutralize Aβ seeds before Aβ deposition becomes detectable in Aβ precursor protein-transgenic mice.

Multimodal analgesia after thyroid or parathyroid surgery: A randomized controlled trial.

Background: The opioid epidemic prompted reevaluation of surgeons' opioid prescribing practices. This study aimed to demonstrate noninferiority of a staged analgesic regimen after endocrine surgery.

Methods: We conducted a randomized controlled trial comparing analgesic regimens after thyroidectomy and/or parathyroidectomy.

A Review of Postoperative Pain Management for Thyroid and Parathyroid Surgery.

Background: Perioperative opioid use has been linked to abuse potential by patients, leading surgeons to scrutinize their postoperative prescribing practices. The goal of the study was to review analgesic regimens for patients undergoing thyroidectomy and parathyroidectomy and extrapolate changes that could be made to decrease opioid use while maintaining adequate pain control.

Materials And Methods: A literature review was performed.

Xenotransplantation of pre-pubertal ovarian cortex and prevention of follicle depletion with anti-Müllerian hormone (AMH).

Objective: To determine whether recombinant AMH (rAMH) could prevent post-transplant follicular depletion by acting on the stemness markers Oct-4, Sox2, and NANOG.

Materials And Methods: This was an experimental study where 12 ovariectomized nude mice were xenotransplanted with vitrified/warmed ovarian cortex obtained from a pre-pubertal girl and Alzet pumps delivering rAMH, or placebo (control), were inserted intra-abdominally. Previously vitrified/warmed ovarian cortex fragments were transplanted after 7 days and then harvested after 14 days from pump placement.

Anti-Müllerian Hormone (AMH) May Stall Ovarian Cortex Function Through Modulation of Hormone Receptors Other Than the AMH Receptor.

Objective: To test whether recombinant anti-Müllerian hormone (AMH) can inhibit ovarian cortex function by modulating the expression of other hormone receptors.

Materials And Methods: Pilot experimental study with ovarian cortex obtained from 5 patients. Immediately after explant, the ovarian cortex specimens were divided into 5 equal fragments.

A safe and effective management strategy for blunt cerebrovascular injury: Avoiding unnecessary anticoagulation and eliminating stroke.

Background: Few injuries have produced as much debate with respect to management as have blunt cerebrovascular injuries (BCVIs). Recent work (American Association for the Surgery of Trauma 2013) from our institution suggested that 64-channel multidetector computed tomographic angiography (CTA) could be the primary screening tool for BCVI. Consequently, our screening algorithm changed from digital subtraction angiography (DSA) to CTA, with DSA reserved for definitive diagnosis of BCVI following CTA-positive study results or unexplained neurologic findings.

Fertility biomarkers to estimate metabolic risks in women with polycystic ovary syndrome.

Purpose: We sought to evaluate the relationship between the polycystic ovary syndrome (PCOS)-defining characteristics and the risk of developing metabolic complications in women presenting with complaints of infertility and/or menstrual irregularities and subsequently diagnosed with PCOS.

Methods: This was a cross-sectional study. Women presenting with complaints of infertility and/or irregular menses and diagnosed with PCOS by the Rotterdam criteria, underwent endocrine, metabolic, and ultrasound assessment in the early follicular phase.

Tissue specific DNA methylation in normal human breast epithelium and in breast cancer.

Cancer is a heterogeneous and tissue-specific disease. Thus, the tissue of origin reflects on the natural history of the disease and dictates the therapeutic approach. It is suggested that tissue differentiation, mediated mostly by epigenetic modifications, could guide tissue-specific susceptibility and protective mechanisms against cancer.

Goserelin fosters bone elongation but does not prevent ovarian damage in cyclophosphamide-treated prepubertal mice.

Objective: To evaluate whether administration of goserelin, a gonadotropin-releasing hormone (GnRH) agonist, could prevent acute or chronic ovarian insufficiency from cyclophosphamide (CTX) administration to prepubertal mice.

Design: Animal study.

Setting: University center.

Somatic and reproductive development in pre-pubertal mice treated with cyclophosphamide and subsequent estrogen replacement.

We tested the hypothesis that chemotherapy would prevent the expected pubertal development of uterus, ovaries, and long bones, and that estrogen replacement subsequent to treatment with chemotherapy would restore uterine and bone development to expected sizes. Pre-pubertal female C57BL/6J mice (n = 78) were assigned to receive placebo (controls), 200 mg/kg (group A), or 120 mg/kg (group B) of cyclophosphamide (CTX) on postnatal day 18. Mice were subsequently randomized to receive estradiol placebo or long-release estradiol pellet insertion on day 22 (early estradiol dose), day 45 (mid estradiol dose), or day 67 (late estradiol dose) of life.

Serum markers of ovarian reserve and ovarian histology in adult mice treated with cyclophosphamide in pre-pubertal age.

Purpose: AMH is used to quantify the extent of follicular pool in postpubertal women, but its value after chemotherapy is unclear. We tested AMH as a marker of follicular reserve in adult mice treated with cyclophosphamide (CTX) in prepubertal age.

Methods: Mice received placebo or CTX at age 18 days.

Endometrial signaling pathways during ovarian stimulation for assisted reproduction technology.

Objective: To determine the effects of different hormonal levels on endometrial biochemical development during ovulation induction for assisted reproduction technology (ART) cycles.

Design: Prospective controlled study.

Setting: University center.

Somatic and reproductive outcomes in mice treated with cyclophosphamide in pre-pubertal age.

Disruption in the normal timing of female puberty, such as in pre-pubertal cancer treatments, can cause abnormal somatic development. We sought to evaluate the impact of cyclophosphamide (CTX) on the somatic, uterine, and ovarian, development of pre-pubertal mice. Pre-pubertal (day 18 of life) C57BL/6J female mice were randomized to receive placebo (group 1A and 1B), 200 mg/kg CTX (group 2A), or 120 mg/kg CTX (group 2B).

Serum DNA methylation for monitoring response to neoadjuvant chemotherapy in breast cancer patients.

Patients with large or nonoperable breast cancers often receive neoadjuvant chemotherapy to facilitate full resection of the tumor and enable conservation of the breast. However, currently available methods for evaluation of response during therapy are limited and the actual effect of the treatment is only recognized at surgery upon completion of chemotherapy. Timely assessment of response could allow individual tailoring of the treatment and save noneffective drugs and unnecessary toxicity.

Assessing the quality of democratic deliberation: a case study of public deliberation on the ethics of surrogate consent for research.

"Deliberative democracy" is an increasingly popular method for soliciting public input on health care policies. There are a number of ways of organizing deliberative democracy (DD) sessions, but they generally involve gathering a group of citizens, supplying them with information relevant to the policy in question, giving them time to interact with each other and with experts in the policy area, and collecting their informed and considered opinions. As the method has become more widely used, some have questioned the quality of the public input it generates.

Deliberative assessment of surrogate consent in dementia research.

Background: Research involving incapacitated persons with dementia entails complex scientific, legal, and ethical issues, making traditional surveys of layperson views on the ethics of such research challenging. We therefore assessed the impact of democratic deliberation (DD), involving balanced, detailed education and peer deliberation, on the views of those responsible for persons with dementia.

Methods: One hundred and seventy-eight community-recruited caregivers or primary decision-makers for persons with dementia were randomly assigned to either an all-day DD session group or a control group.

Fetal transfusion: the spectrum of clinical research in the past year.

Purpose Of Review: Our goal is to review recent articles that examine the current state of fetal transfusion therapy from technique to education.

Recent Findings: Even as technology facilitates physicians' diagnosis and treatment of rare disorders requiring fetal transfusion therapy, longstanding questions remain such as the use of intravascular versus intraperitoneal transfusion sites. However, the recent progress seen with molecular techniques, disease markers, and mathematical models demonstrates that despite unanswered questions, there is much to be hopeful about in improving our understanding of fetal transfusions and their application to a variety of diseases.

Effect of the ABO blood group on the proliferative and clonogenic capacity of umbilical cord stem cells.

Possible effects of the ABO blood group on the proliferative and self-renewal capacity of umbilical cord CD34+ cells were evaluated. A, B and O (all Rh D+) CD34+ cells isolated from three placental blood samples were cultured in four platforms with hematopoietic growth factors on a 3-dimensional biocompatible matrix. Results from this study suggest that proliferation of CD34+ cells with the O phenotype may be greater than that of cells with the A or B phenotypes.

Preferences for life-sustaining treatments in advance care planning and surrogate decision making.

Background: Surrogates and clinicians often make treatment decisions for decisionally incapacitated patients with limited knowledge of their preferences. This study examined patients' life-sustaining treatment preferences to facilitate advance care planning discussions and surrogate decision making.

Methods: We interviewed 342 participants from 7 groups: younger and older well adults; persons with chronic illness, terminal cancer, and acquired immunodeficiency syndrome (AIDS); stroke survivors; and nursing home residents.

Single nucleotide polymorphism map of five long-QT genes.

We screened a white population for single nucleotide polymorphisms (SNPs) in five long QT syndrome genes, namely, KCNQ1 (LQT1), HERG (LQT2), SCN5A (LQT3), KCNE1 (LQT5), and KCNE2 (LQT6). We found 35 SNPs, 10 of which have not been previously described. Ten SNPs were in KCNE1, six in HERG, eight in KCNQ1, four in KCNE2, and seven in SCN5A.

Serum- and glucocorticoid-regulated kinase (SGK1) gene and blood pressure.

The serum- and glucose-regulated kinase (SGK1) gene has recently been identified as an important aldosterone-induced protein kinase that mediates trafficking of the renal epithelial Na(+) channel (ENaC) to the cell membrane. Thus, SGK1 is an appealing candidate for blood pressure regulation and possibly essential hypertension. To test this hypothesis, we recruited monozygotic (126 pairs) and dizygotic (70 pairs) normotensive twin subjects and parents of dizygotic twins.