A modular microfluidic architecture for integrated biochemical analysis

Microfluidic laboratory-on-a-chip (LOC) systems based on a modular architecture are presented. The architecture is conceptualized on two levels: a single-chip level and a multiple-chip module (MCM) system level. At the individual chip level, a multilayer approach segregates components belonging to two fundamental categories: passive fluidic components (channels and reaction chambers) and active electromechanical control structures (sensors and actuators). This distinction is explicitly made to simplify the development process and minimize cost. Components belonging to these two categories are built separately on different physical layers and can communicate fluidically via cross-layer interconnects. The chip that hosts the electromechanical control structures is called the microfluidic breadboard (FBB). A single LOC module is constructed by attaching a chip comprised of a custom arrangement of fluid routing channels and reactors (passive chip) to the FBB. Many different LOC functions can be achieved by using different passive chips on an FBB with a standard resource configuration. Multiple modules can be interconnected to form a larger LOC system (MCM level). We demonstrated the utility of this architecture by developing systems for two separate biochemical applications: one for detection of protein markers of cancer and another for detection of metal ions. In the first case, free prostate-specific antigen was detected at 500 aM concentration by using a nanoparticle-based bio-bar-code protocol on a parallel MCM system. In the second case, we used a DNAzyme-based biosensor to identify the presence of Pb(2+) (lead) at a sensitivity of 500 nM in <1 nl of solution.     

Perineal body length and lacerations at delivery

OBJECTIVE: To define normal perineal body length during labor and determine if a shortened perineal body is associated with perineal lacerations or operative vaginal delivery. STUDY DESIGN: We reviewed charts of patients admitted for labor over a 4-month period. The perineal body was measured by the admitting physician and delivery outcomes obtained from inpatient records. Patients were excluded for malpresentation, multiple gestation, gestational age < 36 weeks, incomplete records and scheduled cesarean delivery. To determine if differences existed between patients with perineal body measurements available and those without, chi2 analysis was used, with P<.05 considered significant. Multiple logistic regression was used to control for confounding variables and determine if a shortened perineal body affected the incidence of operative vaginal delivery and significant lacerations at vaginal delivery. RESULTS: A total of 234 patients met our inclusion criteria; perineal body measurements were available for 133 (57%). The average perineal body length was 3.90 cm (+/-0.70). Patients with a perineal body of < or = 2.5 cm had a significantly higher chance of sustaining a third- or fourth-degree laceration (40% vs. 5.6%, P=.004). This risk remained after controlling for both operative vaginal delivery and episiotomy. The incidence of operative vaginal delivery was greater (28.5% vs. 9.2%, P =.006) for patients with a perineal body < or = 3.5 cm. CONCLUSION: There is an increased risk of significant lacerations and operative vaginal delivery in patients with a shortened perineal body.     

Brief report: health beliefs among survivors of childhood cancer

OBJECTIVE: To describe interest in cancer screening and tobacco-control procedures (nicotine-addiction susceptibility testing) among survivors of childhood cancer and to identify psychosocial modifying and readiness factors associated with survivors' interest, based on the children's health belief model. METHODS: Twenty-eight survivor-mother dyads were interviewed as part of a preliminary study (mean age of survivors = 15.4 years at time of interview, 10.1 years at time of diagnosis, and 12.0 years at end of treatment); interviews consisted of well-validated self-report items and measures of health beliefs. RESULTS: In sum, 57% and 61% of survivors were interested in screening and susceptibility testing, respectively. Survivors who rated themselves as more competent, more concerned about cancer, and more vulnerable to cancer were more interested in participating in screening. Regarding interest in nicotine-addiction susceptibility testing, survivors were more interested when they perceived greater vulnerability to the harm of smoking and when they had mothers who perceived themselves to be in better health. CONCLUSIONS: Preliminary data suggest that psychosocial modifying and readiness factors are associated with survivors' interest in cancer screening and tobacco-control procedures and that additional research in this area is warranted.     

Melanin-concentrating hormone receptor mutations and human obesity: functional analysis

Melanin-concentrating hormone (MCH), a neuropeptide highly expressed in the lateral hypothalamus, has an important role in the regulation of energy balance and body weight in rodents. We examined whether mutations in the two known MCH receptors might be associated with obesity-related phenotypes in humans. Among 106 subjects with severe early onset obesity and a history of hyperphagia, we found two missense variants in MCHR1: Y181H and R248Q. Neither of these was found in 192 normal weight controls. R248Q cosegregated with obesity across two generations; family data were unavailable for Y181H. When expressed in HEK293 cells, R248Q showed no evidence of constitutive activation or ligand hypersensitivity for extracellular signal-regulated kinase phosphorylation. In addition, R248Q showed no enhanced suppression of cAMP generation. Two common single-nucleotide polymorphisms were found to be in linkage disequilibrium: g.-114A>G and c.39C>T. No association between either of these single-nucleotide polymorphisms and obesity-related phenotypes was found among a population cohort of 541 whites. Only two rare noncoding variants were found in MCHR2. In conclusion, mutations in the MCH receptors are not commonly found in humans with severe early onset obesity. Clarification of the relationship of these variants to obesity must await study in other populations and/or in genetically modified mice.     

Eyelid replantation eight months after traumatic avulsion

We present a case in which a lower eyelid avulsed during trauma, was assumed to be lost, and was fortuitously discovered within a fistulous tract in the temporal fascia. The ectopic located lower eyelid was then replanted to its original location. The replanted lower eyelid and several lashes survived. We offer that in the rare instance when eyelid tissue cannot be immediately replanted after injury, temporary ectopic storage and future replantation may be a viable option.     

Treatment options for brain metastases in patients with non-small cell lung cancer

Opinion statement Brain metastases are a common complication for patients with non-small cell lung cancer and a significant cause of morbidity and mortality. In the past, treatment of brain metastases and lung cancer focused on symptom palliation with whole brain radiotherapy (WBRT) and steroids because of the grim outlook for patients. However, recent advances in technology and surgical techniques have created more options for the management of brain metastases, which include surgery, irradiation, stereotactic radiosurgery, and chemotherapy. These aggressive approaches have resulted in an improvement of neurologic outcomes and survival rates of patients with non-small cell lung cancer. Central nervous system (CNS) metastases can be divided into three groups: solitary CNS metastases with controlled or controllable primary disease, oligometastatic disease (fewer than three metastases), and multiple metastases. For patients with solitary CNS metastases, long-term survival is possible. A radical treatment approach involving surgical resection or radiosurgery, followed by WBRT, is recommended. For patients with oligometastatic disease, surgical resection or radiosurgery is considered in selected cases and WBRT is indicated. For patients with multiple metastases, WBRT is recommended. For patients with oligometastatic disease and patients with multiple metastases, recent evidence indicates that systemically effective chemotherapy may produce responses and can be instituted safely before radiotherapy. The treatment timing of chemotherapy and radiotherapy should be individualized.