Surgical margins in head and neck cancer: A contemporary review

Adequate resection margins are critical to the treatment decisions and prognosis of patients with head and neck squamous cell carcinoma (HNSCC). However, there are numerous controversies regarding reporting and interpretation of the status of resection margins. Fundamental issues relating to the basic definition of margin adequacy, uniform reporting standards for margins, optimal method of specimen dissection, and the role of intraoperative frozen section evaluation, all require further clarification and standardization. Future horizons for margin surveillance offer the possible use of novel methods such as “molecular margins” and contact microscopic endoscopy, However, the limitations of these approaches need to be understood. The goal of this review was to evaluate these issues to define a more rational, standardized approach for achieving resection margin adequacy for patients with HNSCC undergoing curative resection. © 2012 Wiley Periodicals, Inc. Head Neck, 2013     

EMTALA obligations for psychiatric patients

The Emergency Medical Treatment and Labor Act (EMTALA) was passed in 1986 and governs the obligations of licensed hospitals that participate in the Medicare program with respect to patients with emergency medical conditions. Psychiatric units and facilities often believe that it does not apply to them, or they are cavalier in their efforts to comply with it. If the entity is a licensed hospital, or operates within a licensed hospital, that participates in Medicare, the Act is fully applicable to them. Such entities disregard EMTALA at their peril.     

Influence of thiopurine S‐methyltransferase polymorphisms in mercaptopurine pharmacokinetics in healthy volunteers

Mercaptopurine is a drug commonly used in the treatment of different types of cancer, especially acute lymphoblastic leukaemia, and autoimmune diseases such as ulcerative colitis or Crohn's disease and in patients receiving organ transplants. It is metabolized by three cytosolic enzymes. One of them, thiopurine S‐methyltransferase (TPMT), is responsible for catalysing the methylation reaction of mercaptopurine to 6‐methylmercaptopurine, thus inactivating the drug. Individuals with TPMT loss‐of‐function alleles (*2, *3A, *3B or *3C) can be extremely sensitive to the effect of mercaptopurine, since it can be accumulated, therefore producing haematological toxicity. The objective of this study was to evaluate the role of TPMT polymorphisms on the pharmacokinetics of mercaptopurine. For that purpose, we used collected pharmacokinetic data from 48 healthy volunteers (all males) who received a single oral dose of mercaptopurine 50 mg in two bioequivalence studies. The volunteers were subsequently genotyped for TPMT *2, *3A, *3B and *3C alleles by real‐time PCR. There were four carriers (8.3%) of TPMT*2 and TPMT*3A alleles. Mercaptopurine elimination was affected by TPMT loss‐of‐function polymorphisms, since heterozygous subjects show 18% higher half‐life compared to wild‐type individuals. This fact is consistent with the expected since the presence of loss‐of‐function alleles decreases TPMT enzymatic activity and, thus, affects mercaptopurine elimination. Moreover, mercaptopurine pharmacokinetic parameters were different among races, since Latins showed higher plasma concentrations and lower clearance compared to Caucasians. This fact might be due to a different distribution of polymorphisms in genes, other than TPMT, that also influence the pharmacokinetics of mercaptopurine.     

New Workforce Development in Dementia Care: Screening for “Caring”: Preliminary Data

The United States has a significant shortage of trained geriatricians and of nurses, social workers, and paraprofessionals educated to care for elderly adults. As the aging population continues to grow, providing high‐quality care will require new models that better address the many needs of aging individuals and their caregivers, using cost‐effective strategies. Responding to this need, the Indiana University Center for Aging Research implementation scientists developed, tested, and are now scaling up a successful collaborative care coordination model for older adults with dementia, depression, or both: the Aging Brain Care program. This model now includes a newly created frontline care provider position, the Care Coordinator Assistant. The Care Coordinator Assistant works with individuals and caregivers to monitor biopsychosocial needs and deliver evidence‐based and individualized care protocols, with close supervision from the registered nurse Care Coordinator. Recognizing that current hiring practices for frontline providers were insufficient to screen for critical abilities expected in this new position, including the ability to express “caring” and empathy, a new screening process was created building on the Multiple Mini Interview (MMI) format. The Care Coordinator Assistant MMI comprised six stations, each created to simulate challenging scenarios that will be frequently encountered and to assess important candidate abilities. Overall, the six‐station MMI, with two to three items per station, provided factorially valid measures and good predictive ability. The process did not appear to be overly burdensome for candidates, and interviewers noted that it was helpful in discriminating between candidates.     

FAM65B is a membrane-associated protein of hair cell stereocilia required for hearing

In a large consanguineous Turkish kindred with recessive nonsyndromic, prelingual, profound hearing loss, we identified in the gene FAM65B (MIM611410) a splice site mutation (c.102-1G>A) that perfectly cosegregates with the phenotype in the family. The mutation leads to exon skipping and deletion of 52-amino acid residues of a PX membrane localization domain. FAM65B is known to be involved in myotube formation and in regulation of cell adhesion, polarization, and migration. We show that wild-type Fam65b is expressed during embryonic and postnatal development stages in murine cochlea, and that the protein localizes to the plasma membranes of the stereocilia of inner and outer hair cells of the inner ear. The wild-type protein targets the plasma membrane, whereas the mutant protein accumulates in cytoplasmic inclusion bodies and does not reach the membrane. In zebrafish, knockdown of fam65b leads to significant reduction of numbers of saccular hair cells and neuromasts and to hearing loss. We conclude that FAM65B is a plasma membrane-associated protein of hair cell stereocilia that is essential for hearing.Hearing loss is the most common sensory problem, affecting approximately 1 in 500 newborns. Most cases are the consequence of mutations in single genes with specific functions in the inner ear (1) (http://hereditaryhearingloss.org). Hearing depends on the ability of the inner ear to convert acoustic waves into electrical signals. This process originates in the stereocilia, actin-rich structures that project from the apical pole of cochlear hair cells and are interconnected in the shape of a staircase to form the hair bundle. Most of the ∼50 hair-bundle proteins identified so far are the products of genes that when mutated lead to hearing loss (2). Thus, the genetic approach has played a major role in elucidating the molecular components of normal hearing.Here we present Family With Sequence Similarity 65, Member B (FAM65B, MIM611410) as a previously unrecognized, plasma membrane-associated protein of hair cell stereocilia. The critical role of FAM65B in human hearing was revealed by genetic analysis of a large family with hereditary deafness. In the zebrafish, knocking down the ortholog of FAM65B led to sensorineural hearing loss.