Partial heart transplantation (PHT) is a novel surgical approach that involves transplantation of only the part of the heart containing a valve. The rationale for this approach is to deliver growing ...heart valve implants that reduce the need for future re-operations in children. However, prior to clinical application of this approach, it was important to assess it in a preclinical model. To investigate PHT short-term outcomes and safety, we performed PHT in a piglet model. Yorkshire piglets (n = 14) were used for PHT of the pulmonary valve. Donor and recipient pairs were matched based on blood types. The piglets underwent PHT at an average age of 44 days (range 34-53). Post-operatively, the piglets were monitored for a period of two months. Of the 7 recipient piglets, one mortality occurred secondary to anesthesia complications while undergoing a routine echocardiogram on post-operative day 19. All piglets had appropriate weight gain and laboratory findings throughout the post-operative period indicating a general state of good health and rehabilitation after undergoing PHT. We conclude that PHT has good short-term survival in the swine model. PHT appears to be safe for clinical application.
Postural orthostatic tachycardia syndrome (POTS) is a chronic and often disabling disorder characterized by orthostatic intolerance with excessive heart rate increase without hypotension during ...upright posture. Patients often experience a constellation of other typical symptoms including fatigue, exercise intolerance and gastrointestinal distress. A typical patient with POTS is a female of child-bearing age, who often first displays symptoms in adolescence. The onset of POTS may be precipitated by immunological stressors such as a viral infection. A variety of pathophysiologies are involved in the abnormal postural tachycardia response; however, the pathophysiology of the syndrome is incompletely understood and undoubtedly multifaceted.
Clinicians and researchers focused on POTS convened at the National Institutes of Health in July 2019 to discuss the current state of understanding of the pathophysiology of POTS and to identify priorities for POTS research. This article, the first of two articles summarizing the information discussed at this meeting, summarizes the current understanding of this disorder and best practices for clinical care.
The evaluation of a patient with suspected POTS should seek to establish the diagnosis, identify co-morbid conditions, and exclude conditions that could cause or mimic the syndrome. Once diagnosed, management typically begins with patient education and non-pharmacologic treatment options. Various medications are often used to address specific symptoms, but there are currently no FDA-approved medications for the treatment of POTS, and evidence for many of the medications used to treat POTS is not robust.
Building on our recent discovery of the zinc signature phenomenon present in boar, bull, and human spermatozoa, we have further characterized the role of zinc ions in the spermatozoa's pathway to ...fertilization. In boar, the zinc signature differed between the three major boar ejaculate fractions, the initial pre-rich, the sperm-rich, and the post-sperm-rich fraction. These differences set in the sperm ejaculatory sequence establish two major sperm cohorts with marked differences in their sperm capacitation progress. On the subcellular level, we show that the capacitation-induced Zn-ion efflux allows for sperm release from oviductal glycans as analyzed with the oviductal epithelium mimicking glycan binding assay. Sperm zinc efflux also activates zinc-containing enzymes and proteases involved in sperm penetration of the zona pellucida, such as the inner acrosomal membrane matrix metalloproteinase 2 (MMP2). Both MMP2 and the 26S proteasome showed severely reduced activity in the presence of zinc ions, through studies using by gel zymography and the fluorogenic substrates, respectively. In the context of the fertilization-induced oocyte zinc spark and the ensuing oocyte-issued polyspermy-blocking zinc shield, the inhibitory effect of zinc on sperm-borne enzymes may contribute to the fast block of polyspermy. Altogether, our findings establish a new paradigm on the role of zinc ions in sperm function and pave the way for the optimization of animal semen analysis, artificial insemination (AI), and human male-factor infertility diagnostics.
Crown-like structures in breast adipose tissue (CLS-B), composed of necrotic adipocytes encircled by macrophages, are associated with obesity and hypothesized to worsen breast cancer prognosis; ...however, data are sparse, particularly in multi-racial populations.
We assessed specimens for CLS-B from 174 African-American and 168 White women with stage I-III breast cancer treated by mastectomy. Benign breast tissue from an uninvolved quadrant was immunohistochemically stained for CD68 to determine CLS-B presence and density (per cm
of adipose tissue). Demographic and lifestyle factors, collected via medical record review, were analyzed for associations with CLS-B using logistic regression. Multivariable Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between CLS-B and overall (OS) or progression-free (PFS) survival.
Detection of any CLS-B was similar between African-American (32%) and White (29%) patients with no evidence of an association between race and CLS-B in multivariable models (OR = 0.82, 95% CI = 0.49-1.36). Detection of CLS-B was associated with obesity (OR = 4.73, 95% CI = 2.48-9.01) and age ≥ 60 years at diagnosis (OR = 1.78, 95% CI = 0.99-3.21). There was some evidence of associations with parity and current smoking status. Detection of CLS-B was not associated with OS (HR = 1.02, 95% CI = 0.55-1.87) or PFS (HR = 0.99, 95% CI = 0.59-1.67).
Our results show a strong, positive association between BMI and CLS-B in non-tumor tissue similar to previous findings. Detection of CLS-B did not vary by race and was not associated with worse OS or PFS.
•Parent report of child receptive and expressive language and fine motor skills is generally consistent with direct assessment.•Child diagnosis does not influence consistency between parent report ...and direct testing.•When disagreement between sources exists, parents are more likely to report a skill as present than seen on direct testing.
There are unique challenges associated with measuring development in early childhood. Two primary sources of information are used: parent report and direct assessment. Each approach has strengths and weaknesses, particularly when used to identify and diagnose developmental delays. The present study aimed to evaluate consistency between parent report and direct assessment of child skills in toddlers with and without Autism Spectrum Disorder (ASD) across receptive language, expressive language, and fine motor domains.
109 children were evaluated at an average age of two years; data on child skills were collected via parent report and direct assessment. Children were classified into three groups (i.e., ASD, Other Developmental Disorder, or Typical Development) based on DSM-IV-TR diagnosis. Mixed design ANOVAs, with data source as a within subjects factor and diagnostic group as a between subjects factor, were used to assess agreement. Chi square tests of agreement were then used to examine correspondence at the item level.
Results suggested that parent report of language and fine motor skills did not significantly differ from direct assessment, and this finding held across diagnostic groups. Item level analyses revealed that, in most cases of significant disagreement, parents reported a skill as present, but it was not seen on direct testing.
Results indicate that parents are generally reliable reporters of child language and fine motor abilities in toddlerhood, even when their children have developmental disorders such as ASD. However, the fullest picture may be obtained by using both parent report and direct assessment.
Some children with autism spectrum disorders (ASDs) exhibit low mental age (Low-MA; i.e., cognitive functioning below 12 months). We examined diagnosis, symptom severity, and development in children ...with ASD-low MA (
n
= 25), autistic disorder (
n
= 111), and PDD-NOS (
n
= 82) at ages two and four. We predicted that some ASD-low MA children would demonstrate just intellectual impairment and not autism symptoms on follow-up, with social deficits at age two attributable to global delays. Instead, most ASD-low MA children (96%) had an ASD at follow-up, compared to children initially diagnosed with autistic disorder (86.5%) or PDD-NOS (73.2%). They showed the least developmental progress and highest symptom severity. Results support diagnosing ASDs in children functioning below a 12-month level.
ACC is a rare malignant tumor of the salivary glands. In this contemporary review, we explore advances in identification of targetable alterations and clinical trials testing these druggable targets. ...A search of relevant articles and abstracts from national meetings and three databases, including PubMed, Medline, and Web of Science, was performed. Following keyword search analysis and double peer review of abstracts to ensure appropriate fit, a total of 55 manuscripts were included in this review detailing advances in molecular targets for ACC. The most researched pathway associated with ACC is the MYB-NFIB translocation, found to lead to dysregulation of critical cellular pathways and thought to be a fundamental driver in a subset of ACC disease pathogenesis. Other notable molecular targets that have been studied include the cKIT receptor, the EGFR pathway, and NOTCH1, all with limited efficacy in clinical trials. The ongoing investigation of molecular abnormalities underpinning ACC that may be responsible for carcinogenesis is critical to identifying and developing novel targeted therapies.
We describe a remote access thyroidectomy technique: robotic thyroidectomy via posterior neck approach using the Da Vinci single port (Sp) robotic system. This approach is feasible and safe in the ...Western population.
Laryngoscope, 134:2779–2782, 2024
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