Human metabolism: pathways and clinical aspects

Metabolism describes the series of chemical reactions that are concerned with the provision of energy to biological systems. They may be divided into reactions involved in energy yield (catabolism: demand exceeds supply), and energy storage (anabolism: supply exceeds demand). Regulation of these pathways is critical for homeostasis, and derangements in metabolism are seen in a wide variety of pathological processes. Understanding metabolism is key to the treatment of many diseases, notably diabetes, as well as underpinning clinical nutritional support.     

Epithelial ovarian cancer risk: A review of the current genetic landscape

Ovarian cancer is the fourth most common cause of cancer-related death in women in the developed world, and one of the most heritable cancers. One of the most significant risk factors for epithelial ovarian cancer (EOC) is a family history of breast and/or ovarian cancer. Combined risk factors can be used in models to stratify risk of EOC, and aid in decisions regarding risk-reduction strategies. Germline pathogenic variants in EOC susceptibility genes including those involved in homologous recombination and mismatch repair pathways are present in approximately 22% to 25% of EOC. These genes are associated with an estimated lifetime risk of EOC of 13% to 60% for BRCA1 variants and 10% to 25% for BRCA2 variants, with lower risks associated with remaining genes. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) thought to explain an additional 6.4% of the familial risk of ovarian cancer, with 34 susceptibility loci identified to date. However, an unknown proportion of the genetic component of EOC risk remains unexplained. This review comprises an overview of individual genes and SNPs suspected to contribute to risk of EOC, and discusses use of a polygenic risk score to predict individual cancer risk more accurately.     

Embryonic skull development in the gecko,Tarentola annularis (Squamata: Gekkota: Phyllodactylidae)

Tarentola annularis is a climbing gecko with a wide distribution in Africa north of the equator. In the present paper, we describe the development of the osteocranium of this lizard, from the first appearance of the cranial elements up to the point of hatching. This is based on a combination of histology and cleared and stained specimens. This is the first comprehensive account of gekkotan pre-hatching skull development based on a comprehensive series of embryos, rather than a few selected stages. Given that Gekkota is now widely regarded as representing the sister group to other squamates, this account helps to fill a significant gap in the literature. Moreover, as many authors have considered features of the gekkotan skull and skeleton to be indicative of paedomorphosis, it is important to know whether this hypothesis is supported by delays in the onset of cranial ossification. In fact, we found the sequence of cranial bone ossification to be broadly comparable to that of other squamates studied to date, with no significant lags in development.     

Intimate partner violence as a mechanism of traumatic ocular injury in women

ObjectiveDetermine the prevalence of intimate partner violence (IPV) as a mechanism of traumatic ocular injury in women, typical injury patterns, and the clinical course of affected patients. Encourage IPV screening and safety assessment in patients presenting with characteristic ocular trauma.MethodsMedical records of 211 female patients with traumatic ocular injuries evaluated at the University of Iowa Hospitals and Clinics between January 1995 and January 2015 were reviewed to determine the rate of IPV as a mechanism of ocular trauma. Twenty-one patients were excluded due to no documented trauma.ResultsLeading causes of traumatic ocular injuries in the 190 female patients included were accidental trauma with an inanimate object (n = 70/190, 36.8%), falls (n = 52/190, 27.4%), motor vehicle collisions (n = 21/190, 11.1%), and assault (n = 16/190, 8.4%). In 2.1% of cases (n = 4/190), no mechanism of traumatic injury was documented. Assault was the fourth leading mechanism of injury accounting for 8.4% of cases (n = 16/190), with IPV accounting for more than one third of cases with a documented perpetrator (n = 5/13). No perpetrator was documented in 18.8% (n = 3/16). All 5 patients with IPV-related injuries sustained scleral laceration or rupture; 4 out of 5 patients had no light perception vision and ultimately required enucleation.ConclusionIPV is an important mechanism of traumatic ocular injury. IPV-associated injuries tend to be severe in nature, as demonstrated by the high rate of globe laceration or rupture and subsequent enucleation in the study population. By appropriate screening and referral, ophthalmologists have an opportunity to redirect a potentially devastating course.     

Oral beta2-agonist use by preschool children with asthma in East and Central Harlem, New York.

Although studies have documented underuse of controller medications and overuse of short-acting inhaled ss(2)-agonist among children with persistent asthma in disadvantaged communities, the persistence of oral ss(2)-agonist use in pediatric practice has not been studied since inhaled short-acting ss(2)-agonists became widespread. We describe medications used to treat asthma among children 3 to 5 years of age at 10 Head Start and other subsidized preschool centers in East and Central Harlem, New York City. We interviewed 149 parents/guardians of children who were identified as having probable asthma based on physician's diagnosis, persistent symptoms, hospitalization, and medication use. We classified 86 of the 149 children (58%) as having current persistent asthma. Only 15 of them (17%) were reported to have used controller medications at least 5 days/week in the last 4 weeks-only 2 of whom used inhaled corticosteroids. By contrast, 53 children (62%) used oral ss(2)-agonist in the last 4 weeks, often (72%) in conjunction with nebulized or inhaled short-acting ss(2)-agonist. Use of oral ss(2)-agonist was associated with more severe symptoms. This study documents the continued widespread use of oral ss(2)-agonist for treatment of children in a low-income community with high prevalence of asthma.     

Academic Degrees and Clinical Practice Characteristics: The University of Washington Physician Assistant Program: 1969-2000

CONTEXT: The physician assistant profession has been moving toward requiring master's degrees for new practitioners, but some argue this could change the face of the discipline. PURPOSE: To see if there is an association between physician assistants' academic degrees and practice in primary care, in rural areas, and with the medically underserved. METHODS: Surveys were sent to 880 graduates of the first 32 University of Washington physician assistant classes through 2000. Respondents noted their academic degree at program entry and the highest degree attained at any time up to the time of survey. Relationships between practice characteristics and academic degree levels were tested by unadjusted odds ratios and logistic regression after controlling for year of graduation and sex. RESULTS: Of the 478 respondents, 54% worked in primary care, about 30% practiced in nonmetropolitan communities, and 42% reported providing care for the medically underserved. Respondents with no degree (33% of total at entry, 24% at survey) were significantly more likely than degree holders to work in primary care and nonmetropolitan areas. Respondents with no degree at program entry were significantly more likely, and those with no degree at the time of the survey were marginally more likely, to self-report work with the medically underserved. CONCLUSION: Respondents with no academic degree are significantly more likely to demonstrate a commitment to primary, rural, and underserved health care. These findings may inform the national debate about the impact of required advanced degrees on the practice patterns of nonphysician providers.