Retinopathy of prematurity

Over the last decade major advances have been made in the understanding of the pathogenesis and evolution of retinopathy of prematurity (ROP). The increased survival of very small premature infants in modern neonatal intensive care units has led to the resurgence of this potentially blinding disease. ROP appears to be a multifactorial disease, the prevention of which is probably impossible even now, with the most accurate methods of blood gas monitoring and oxygen restriction. In addition to oxygen, there are a number of significant risk factors, such as birth weight and gestational age, ventilator hours, hyper and hypocarbia, hypoxia and acidosis, xanthine therapy and probably bright light. Current data suggest that the level of antioxidants in the immature retina is relatively low and therefore oxygen radicals which accumulate in the preterm baby's retina may play an important role in the pathogenesis of ROP. The treatment of the disease in both its "active" and "cicatricial" stages emphasizes the need for a new classification which could serve as a common international language through which results may be compared. Vitamin E was suggested in some studies to be helpful in preventing the severe stages of the disease, but its efficacy has yet to be proved. Treatment modalities such as photocoagulation, cryotherapy and vitrectomy are being tried as a means of therapy in the more advanced stages of the disease. Preliminary results of a large multicenter study support the efficacy of cryotherapy.     

Exploring the Phenomenon of Spiritual Care Between Hospital Chaplains and Hospital Based Healthcare Providers

Hospital chaplaincy and spiritual care services are important to patients’ medical care and well-being; however, little is known about healthcare providers’ experiences receiving spiritual support. A phenomenological study examined the shared experience of spiritual care between hospital chaplains and hospital-based healthcare providers (HBHPs). Six distinct themes emerged from the in-depth interviews: Awareness of chaplain availability, chaplains focus on building relationships with providers and staff, chaplains are integrated in varying degrees on certain hospital units, chaplains meet providers’ personal and professional needs, providers appreciate chaplains, and barriers to expanding hospital chaplains’ services. While HBHPs appreciated the care received and were able to provide better patient care as a result, participants reported that administrators may not recognize the true value of the care provided. Implications from this study are applied to hospital chaplaincy clinical, research, and training opportunities.     

Preliminary field trial of a radioimmunoassay for the diagnosis of malaria

A radioimmunoassay (RIA) has been developed for the detection of Plasmodium falciparum in infected blood. The assay is based on the ability of solubilized, infected red blood cells (RBC) (P. falciparum "antigen") to combine with anti-P. falciparum antibodies and thus prevent the subsequent interaction of the latter with "antigen"-coated microtiter plates. A preliminary trial was carried out in Thailand to determine the usefulness of the RIA for the immunodiagnosis of malaria. Blood samples from malarious and non-malarious patients were examined both by standard microscopy and by RIA. Efficient solubilization of the parasites proved to be a major requirement for the successful performance of the RIA. Sonication or freezing and thawing, which were perfectly satisfactory for the solubilization of cultured, infected RBC, were found to be totally inadequate when applied to RBC taken from patients. However, parasites in RBC from patients could be solubilized efficiently by treatment with detergents (e.g., NP40, Triton X-100, etc.). Of the 108 blood samples tested, 23 were found positive for falciparum parasitemia by microscopy and 39 by RIA. One sample from a patient with patent falciparum parasitemia and three with patent vivax parasitemia were negative by RIA. Ten of the samples positive only by RIA belonged to patients with recent malarial infection, as shown by microscopy. Thus, the RIA detected almost all of the patients with microscopic evidence of falciparum malaria. The proportion of false positives in the RIA test was low.     

Molecular diagnosis of resistance to antimalarial drugs during epidemics and in war zones

Plasmodium falciparum mutations pfcrt K76T and the dhfr/dhps "quintuple mutant" are molecular markers of resistance to chloroquine and sulfadoxine-pyrimethamine, respectively. During an epidemic of P. falciparum malaria in an area of political unrest in northern Mali, where standard efficacy studies have been impossible, we measured the prevalence of these markers in a cross-sectional survey. In 80% of cases of infection, pfcrt K76T was detected, but none of the cases carried the dhfr/dhps quintuple mutant. On the basis of these results, chloroquine was replaced by sulfadoxine-pyrimethamine in control efforts. This example illustrates how molecular markers for drug resistance can provide timely data that inform malaria-control policy during epidemics and other emergency situations.     

Biomechanics of milk extraction during breast-feeding

How do infants extract milk during breast-feeding? We have resolved a century-long scientific controversy, whether it is sucking of the milk by subatmospheric pressure or mouthing of the nipple–areola complex to induce a peristaltic-like extraction mechanism. Breast-feeding is a dynamic process, which requires coupling between periodic motions of the infant’s jaws, undulation of the tongue, and the breast milk ejection reflex. The physical mechanisms executed by the infant have been intriguing topics. We used an objective and dynamic analysis of ultrasound (US) movie clips acquired during breast-feeding to explore the tongue dynamic characteristics. Then, we developed a new 3D biophysical model of the breast and lactiferous tubes that enables the mimicking of dynamic characteristics observed in US imaging during breast-feeding, and thereby, exploration of the biomechanical aspects of breast-feeding. We have shown, for the first time to our knowledge, that latch-on to draw the nipple–areola complex into the infant mouth, as well as milk extraction during breast-feeding, require development of time-varying subatmospheric pressures within the infant’s oral cavity. Analysis of the US movies clearly demonstrated that tongue motility during breast-feeding was fairly periodic. The anterior tongue, which is wedged between the nipple–areola complex and the lower lips, moves as a rigid body with the cycling motion of the mandible, while the posterior section of the tongue undulates in a pattern similar to a propagating peristaltic wave, which is essential for swallowing.Breast-feeding is strongly publicized and encouraged by many societies and communities. It is well accepted that breast milk provides the infant both nutrients and immunities required for growth and development during the first months after birth. It is less known that breast-fed infants exercise and prepare their orofacial muscles for future tasks of speaking and chewing (1), and also have higher oxygen saturation than bottle-fed infants (2). Breast-feeding is the outcome of a dynamic synchronization between oscillation of the infant’s mandible, rhythmic motility of the tongue, and the breast milk ejection reflex that drives maternal milk toward the nipple outlet. First, the infant latches onto the breast and nipple so that the nipple, areola, and underlying mammary tissue and lactiferous ducts are drawn into the infant’s mouth with the nipple tip extended as far as the hard–soft palate junction (HSPJ). Then, the infant moves its mandible up and down, compressing the areola and the underlying lactiferous ducts with its gums in a suckling process that extracts the milk into its mouth (3, 4). Simultaneous with compression, spontaneous undulating motions of the infant tongue channel the milk posteriorly and trigger the swallowing reflex (5). During breast-feeding, suckling, swallowing, and breathing are coordinated by the central nervous system in a way that allows for the infant’s continuous feeding without breathing interruptions (2, 6, 7).The physical mechanisms that enable the infant to extract milk from the breast have intrigued scientists for more than a century (8). The two proposed mechanisms that have been a subject of scientific controversy to this day are (i) sucking—emptying of the nipple–breast contents by development of subatmospheric pressures within the infant oral cavity (9–12) and (ii) mouthing—squeezing out of the nipple–areola contents by compression between the jaws or other mouth parts (3). With the appearance of cine–X-ray and ultrasound (US) imaging modalities, a significant role was also attributed to tongue undulation which was naturally referred to as “tongue peristalsis” while chewing the nipple (13, 14). However, advanced computational modeling has not yet been used along with imaging data to perform hypothesis testing on the underlying explanations of the suckling behavior during breast-feeding.We have explored the physical aspects of infant feeding via noninvasive visualizations of the moving components in the oral cavity and a biophysical model. An objective dynamic analysis of submental US imaging of the midsagittal cross-section of the oral cavity during infant feeding was used to study the dynamic characteristics of tongue motion with respect to the rigid upper palate. A 3D fluid–structure interaction (FSI) biophysical model was developed to simulate milk extraction during breast-feeding.     

Management of facial and periocular dog bites: a review of 104 cases

Background

Dog bites are a frequent cause of facial and periocular injuries in both children and adults. This aim of this study is to review current practice in the management of facial and periorbital dog bite injuries and to examine the current evidence-base for such treatment strategies.

Methods

Five hundred eighty-seven patients with dog bite injuries requiring surgical intervention were identified from operating theatre records in one tertiary centre over a 9-year period. A retrospective case note review of 104 patients with facial and periorbital dog bite injuries was performed. Data on patient demographics, type of injury, treatment, and outcome was collected and analysed.

Results

The majority of patients were children, with a mean age of 11 years (range 1–91 years). Injuries involved the cheek in 57 cases (55 %), eyelids in 17 cases (16 %), lips in 24 cases (23 %) and nose in 8 cases (8 %). No facial fractures, canalicular, or globe injuries were recorded. All patients underwent irrigation, debridement, and primary wound closure. Surgical repair occurred within 24 h in 19 cases (18.2 %), within 48 h in 71 cases (68.3 %) and within 5 days in 14 cases (13.4 %). Three patients (2.9 %) developed a wound infection. Two patients (1.9 %) required scar revision surgery.

Conclusions

Periorbital and facial dog bite injuries may result in considerable morbidity. However, the majority of injuries are superficial and canalicular injury and bony injury is uncommon. Early wound irrigation, debridement and primary closure results in a good cosmetic outcome with a low risk of infection.

Level of Evidence:

Level IV, risk/prognostic study.     

Sequencing‐based microsatellite instability testing using as few as six markers for high‐throughput clinical diagnostics

Microsatellite instability (MSI) testing of colorectal cancers (CRCs) is used to screen for Lynch syndrome (LS), a hereditary cancer‐predisposition, and can be used to predict response to immunotherapy. Here, we present a single‐molecule molecular inversion probe and sequencing‐based MSI assay and demonstrate its clinical validity according to existing guidelines. We amplified 24 microsatellites in multiplex and trained a classifier using 98 CRCs, which accommodates marker specific sensitivities to MSI. Sample classification achieved 100% concordance with the MSI Analysis System v1.2 (Promega) in three independent cohorts, totaling 220 CRCs. Backward–forward stepwise selection was used to identify a 6‐marker subset of equal accuracy to the 24‐marker panel. Assessment of assay detection limits showed that the 24‐marker panel is marginally more robust to sample variables than the 6‐marker subset, detecting as little as 3% high levels of MSI DNA in sample mixtures, and requiring a minimum of 10 template molecules to be sequenced per marker for >95% accuracy. BRAF c.1799 mutation analysis was also included to streamline LS testing, with all c.1799T>A variants being correctly identified. The assay, therefore, provides a cheap, robust, automatable, and scalable MSI test with internal quality controls, suitable for clinical cancer diagnostics.     

Valor pronóstico de la ruta de EGFR-PI3K-pAKT-mTOR-pS6 en los carcinomas epidermoides nasosinusales

Background and objectives

We have previously indicated that EGFR has a role in carcinogenesis in a subgroup of sinonasal squamous cell carcinomas (SNSCC). In addition, EGFR activates 2 of the most important intracellular signalling pathways: PI3K/pAKT/mTOR/pS6 and MAP pathway kinases. The objective of this study was to evaluate the involvement of the EGFR/PI3K/pAKT/mTOR/pS6 pathway and its relationship with clinical-pathological parameters and follow-up of sinonasal squamous cell carcinoma.