Older age, male sex, and cerebral microbleeds predict white matter loss after traumatic brain injury.

Little is known on how mild traumatic brain injury affects white matter based on age at injury, sex, cerebral microbleeds, and time since injury. Here, we study the fractional anisotropy of white matter to study these effects in 109 participants aged 18-77 (46 females, age μ ± σ = 40 ± 17 years) imaged within [Formula: see text] 1 week and [Formula: see text] 6 months post-injury. Age is found to be linearly associated with white matter degradation, likely due not only to injury but also to cumulative effects of other pathologies and to their interactions with injury.

Dietary and Genetic Cholesterol Loading Rather Than Steatosis Promotes Liver Tumorigenesis and NASH-Driven HCC.

The association of nonalcoholic steatohepatitis (NASH) with obesity and type 2 diabetes is a major determinant factor for the continued rise of NASH-driven HCC. Unfortunately, the mechanisms underlying the progression from NASH to HCC are not well-understood. Steatosis is characterized by the accumulation of different lipid species, and cholesterol has emerged as an important player in NASH development, which has been shown to promote NASH-driven HCC.

The Indigenous South American Tsimane Exhibit Relatively Modest Decrease in Brain Volume With Age Despite High Systemic Inflammation.

Brain atrophy is correlated with risk of cognitive impairment, functional decline, and dementia. Despite a high infectious disease burden, Tsimane forager-horticulturists of Bolivia have the lowest prevalence of coronary atherosclerosis of any studied population and present few cardiovascular disease (CVD) risk factors despite a high burden of infections and therefore inflammation. This study (a) examines the statistical association between brain volume (BV) and age for Tsimane and (b) compares this association to that of 3 industrialized populations in the United States and Europe.

Endoplasmic Reticulum Stress-Induced Upregulation of STARD1 Promotes Acetaminophen-Induced Acute Liver Failure.

Background & Aims: Acetaminophen (APAP) overdose is a major cause of acute liver failure (ALF). Mitochondrial SH3BP5 (also called SAB) and phosphorylation of c-Jun N-terminal kinase (JNK) mediate the hepatotoxic effects of APAP. We investigated the involvement of steroidogenic acute regulatory protein (STARD1), a mitochondrial cholesterol transporter, in this process and sensitization by valproic acid (VPA), which depletes glutathione and stimulates steroidogenesis.

Cellular metabolites enhance the light sensitivity of Arabidopsis cryptochrome through alternate electron transfer pathways.

Cryptochromes are blue light receptors with multiple signaling roles in plants and animals. Plant cryptochrome (cry1 and cry2) biological activity has been linked to flavin photoreduction via an electron transport chain comprising three evolutionarily conserved tryptophan residues known as the Trp triad. Recently, it has been reported that cry2 Trp triad mutants, which fail to undergo photoreduction in vitro, nonetheless show biological activity in vivo, raising the possibility of alternate signaling pathways.

Human cryptochrome-1 confers light independent biological activity in transgenic Drosophila correlated with flavin radical stability.

Cryptochromes are conserved flavoprotein receptors found throughout the biological kingdom with diversified roles in plant development and entrainment of the circadian clock in animals. Light perception is proposed to occur through flavin radical formation that correlates with biological activity in vivo in both plants and Drosophila. By contrast, mammalian (Type II) cryptochromes regulate the circadian clock independently of light, raising the fundamental question of whether mammalian cryptochromes have evolved entirely distinct signaling mechanisms.

Morgellons disease and delusions of parasitosis.

Morgellons disease is a controversial and poorly defined symptom cluster of skin lesions and somatic symptoms, most notably 'fibers' in the skin. Because of widespread coverage in the media and on the Internet, there are an increasing number of patients presenting to dermatologists. We present three patients who believed that they had fibers in their skin.

Delusional disorders in dermatology: a brief review.

There are several unique psychiatric disorders that are likely to present to a dermatologist because of their accompanying skin complaints. Delusions of parasitosis (DP) is a fixed, false belief of parasitic infestation that may lead patients to compulsively self-mutilate while attempting to remove the non-existent parasites. Morgellons disease is a controversial condition characterized by a fixed belief that fibers that are imbedded or extruding from the skin; this condition is likely in the spectrum of DP.

Kaposi varicelliform eruption (eczema herpeticum).

A 35-year-old woman with a history of atopic diathesis presented to the emergency department with 2 weeks of widespread facial vesiculopustules and eroded vesicles. HSV-1 was found on viral culture and direct fluorescent antibody testing. She was diagnosed with eczema herpeticum, an uncommon and potentially life-threatening viral infection that arises in areas of pre-existing dermatosis.

Severe drug hypersensitivity reaction in a young woman treated with doxycycline.

Doxycycline is a commonly prescribed medication for the management of acne vulgaris. Severe adverse reactions to this medication are uncommon. We describe an unusual case of a 20-year-old female who experienced a life-threatening hypersensitivity reaction, including fever, lymphadenopathy, hepatitis, nephritis and severe pneumonitis with respiratory failure following oral administration of doxycycline for facial acne.

Keloids: pathophysiology and management.

Keloid formation occurs as a result of abnormal wound healing. Despite the high prevalence of keloids in the general population, they remain one of the more challenging dermatologic conditions to manage. More than a cosmetic nuisance, they are often symptomatic and can have a significant psychosocial burden for the patient.

Neonatal lupus.

An otherwise healthy 5-week-old infant with erythematous plaques predominantly on the face and scalp presented to our dermatology clinic. The mother had been diagnosed with lupus erythematosus 2 years earlier but her disease was quiescent. Neonatal lupus is a rare condition associated with transplacental transfer of IgG anti-SSA/Ro and anti-SSB/La antibodies from the mother to the fetus.

Abnormal wound healing: keloids.

Wound healing is a complex and carefully regulated physiologic response to a traumatic injury. Deregulation of this coordinated process can lead to exuberant scar formation as seen in keloids and hypertrophic scars. Despite their common occurrence, keloids remain one of the most challenging dermatologic conditions to successfully treat and may have significant psychosocial impact for the patient.

West Nile virus infection in the pediatric population.

In 2004, Los Angeles County confirmed 11 cases of symptomatic West Nile virus (WNV) infections in children younger than 18 years of age. Eight had WNV fever, 2 had meningitis and 1 had encephalitis. Fever, rash, nausea and vomiting were the most prominent symptoms at presentation; median duration of illness was 7 days.

Homozygosity for premature stop codon of the MHC class I chain-related gene A (MIC-A) is associated with early activation of islet autoimmunity of DR3/4-DQ2/8 high risk DAISY relatives.

We hypothesized that homozygosity for the major histocompatibility complex (MHC) class I chain-related gene A (MIC-A)5.1 allele with premature stop codon would increase diabetes risk of individuals followed from infancy in the DAISY study (Diabetes Autoimmunity Study in the young). Forty five percent (10/22) of relatives (siblings and offspring cohort, SOC) who developed anti-islet autoantibodies were MIC-A5.

"Extended" A1, B8, DR3 haplotype shows remarkable linkage disequilibrium but is similar to nonextended haplotypes in terms of diabetes risk.

To evaluate potential differential diabetes risk of DR3 haplotypes we have evaluated class I alleles as well as two microsatellites previously associated with differential risk associated with DR3 haplotypes. We found that over one-third of patient DR3 chromosomes consisted of an extended DR3 haplotype, from DQ2 to D6S2223 (DQ2, DR3, D6S273-143, MIC-A5.1, HLA-B8, HLA-Cw7, HLA-A1, and D6S2223-177) with an identical extended haplotype in controls.

Insulin autoimmunity: prediction/precipitation/prevention type 1A diabetes.

Type 1 diabetes of both the NOD mouse and man is associated with autoimmunity directed against insulin which is the only beta cell specific autoantigen identified to date. One can use autoantibodies to insulin to predict diabetes, use insulin peptides to create insulin autoantibodies, insulitis and diabetes, and use insulin or its peptides in animal models to prevent diabetes. An expanding set of resources are now available for the development and testing in man of therapies to prevent type 1 diabetes, and a number of trials utilizing insulin peptides are now underway.

Insulin autoantibodies are associated with islet inflammation but not always related to diabetes progression in NOD congenic mice.

Susceptibility to diabetes in humans and nonobese diabetic (NOD) mice is believed to arise from the combined effect of multiple genetic loci, resulting in immune-mediated destruction of the insulin-secreting beta-cells. Insulin autoantibodies (IAAs) are often present in humans for years, and in NOD mice for weeks, before the onset of diabetes. We have evaluated the expression of IAAs in NOD mice and in diabetes-resistant NOD congenic strains to characterize the association of autoantibody expression with insulitis and diabetes.

The genetics of autoimmune polyendocrine syndrome type II.

A series of autoimmune disorders, often Addison's disease, type 1 diabetes mellitus, and thyroid autoimmunity, frequently occurs together in patients with the autoimmune polyendocrine syndrome type II (APS-II). The highest risk HLA genotype for Addison's disease, either as a single disease or in APS-II patients, consists of the genotype DR3/4, DQ2/DQ8 with DRB1*0404. As many as 30% of patients with Addison's disease have this genotype versus less than 0.

Immunology primer.

The immune system, through a complex interplay of highly specialized cells and a seemingly endless number of soluble mediators, works to ensure protection from the potentially harmful pathogens that we encounter in our lifetime. The development of the immune system is a compromise between the necessity to recognize foreign peptides in the context of self-molecules (MHC) and the need to be tolerant to all self-peptides. Despite the large number of mechanisms in place to ensure the removal or suppression of self-reactive lymphocytes, the system is not 100% effective, with the occasional result of autoimmunity.

Millennium award recipient contribution. Identification of children with early onset and high incidence of anti-islet autoantibodies.

A total of 21,000 general population newborns (NECs) and 693 young siblings-offspring of patients with type 1A diabetes (SOCs) were class II genotyped and 293 NECs and 72 SOCs with the high-risk genotype, DR3/4, DQB1*0302 have been prospectively evaluated. Seventeen individuals who converted to persistent autoantibody positivity and two autoantibody-negative control groups (35 SOCs and 24 NECs) were typed for HLA-A class I alleles. The A1, A2 genotype was significantly increased among the autoantibody-positive subjects (47%) compared to autoantibody-negative SOCs (14%, P = 0.