Interpersonal Mechanisms Contributing to the Association Between HIV-Related Internalized Stigma and Medication Adherence.

Previous research suggests that people living with HIV (PLWH) sometimes internalize HIV-related stigma existing in the community and experience feelings of inferiority and shame due to their HIV status, which can have negative consequences for treatment adherence. PLWH's interpersonal concerns about how their HIV status may affect the security of their existing relationships may help explain how internalized stigma affects adherence behaviors. In a cross-sectional study conducted between March 2013 and January 2015 in Birmingham, AL, 180 PLWH recruited from an outpatient HIV clinic completed previously validated measures of internalized stigma, attachment styles, and concern about being seen while taking HIV medication. Participants also self-reported their HIV medication adherence. Higher levels of HIV-related internalized stigma, attachment-related anxiety (i.e., fear of abandonment by relationship partners), and concerns about being seen by others while taking HIV medication were all associated with worse medication adherence. The effect of HIV-related internalized stigma on medication adherence was mediated by attachment-related anxiety and by concerns about being seen by others while taking HIV medication. Given that medication adherence is vitally important for PLWH to achieve long-term positive health outcomes, understanding interpersonal factors affecting medication adherence is crucial. Interventions aimed at improving HIV treatment adherence should address interpersonal factors as well as intrapersonal factors.

MAOA expression predicts vulnerability for alcohol use.

The role of the monoamines dopamine (DA) and serotonin (5HT) and the monoamine-metabolizing enzyme monoamine oxidase A (MAOA) have been repeatedly implicated in studies of alcohol use and dependence. Genetic investigations of MAOA have yielded conflicting associations between a common polymorphism (MAOA-LPR) and risk for alcohol abuse. The present study provides direct comparison of tissue-specific MAOA expression and the level of alcohol consumption. We analyzed rhesus macaque MAOA (rhMAOA) expression in blood from males before and after 12 months of alcohol self-administration. In addition, nucleus accumbens core (NAc core) and cerebrospinal fluid (CSF) were collected from alcohol access and control (no alcohol access) subjects at the 12-month time point for comparison. The rhMAOA expression level in the blood of alcohol-naive subjects was negatively correlated with subsequent alcohol consumption level. The mRNA expression was independent of rhMAOA-LPR genotype and global promoter methylation. After 12 months of alcohol use, blood rhMAOA expression had decreased in an alcohol dose-dependent manner. Also after 12 months, rhMAOA expression in the NAc core was significantly lower in the heavy drinkers, as compared with control subjects. The CSF measured higher levels of DA and lower DOPAC/DA ratios among the heavy drinkers at the same time point. These results provide novel evidence that blood MAOA expression predicts alcohol consumption and that heavy alcohol use is linked to low MAOA expression in both the blood and NAc core. Together, the findings suggest a mechanistic link between dampened MAOA expression, elevated DA and alcohol abuse.

Mechanisms of hemolysis-associated platelet activation.

BACKGROUND: Intravascular hemolysis occurs after blood transfusion, in hemolytic anemias, and in other conditions, and is associated with hypercoagulable states. Hemolysis has been shown to potently activate platelets in vitro and in vivo, and several mechanisms have been suggested to account for this, including: (i) direct activation by hemoglobin (Hb); (ii) increase in reactive oxygen species (ROS); (iii) scavenging of nitric oxide (NO) by released Hb; and (iv) release of intraerythrocytic ADP. OBJECTIVE: To elucidate the mechanism of hemolysis-mediated platelet activation. METHODS: We used flow cytometry to detect PAC-1 binding to activated platelets for in vitro experiments, and a Siemens' Advia 120 hematology system to assess platelet aggregation by using platelet counts from in vivo experiments in a rodent model. RESULTS: We found that Hb did not directly activate platelets. However, ADP bound to Hb could cause platelet activation. Furthermore, platelet activation caused by shearing of red blood cells (RBCs) was reduced in the presence of apyrase, which metabolizes ADP to AMP. The use of ROS scavengers did not affect platelet activation. We also found that cell-free Hb enhanced platelet activation by abrogating the inhibitory effect of NO on platelet activation. In vivo infusions of ADP and purified (ADP-free) Hb, as well as hemolysate, resulted in platelet aggregation, as shown by decreased platelet counts. CONCLUSION: Two primary mechanisms account for RBC hemolysis-associated platelet activation: ADP release, which activates platelets; and cell-free Hb release, which enhances platelet activation by lowering NO bioavailability.

Genome-wide linkage scan for psoriasis susceptibility loci in multiplex Tunisian families.

BACKGROUND: Psoriasis is a relapsing chronic inflammatory skin disease affecting all population groups, with a peak prevalence of 3% in northern European and Scandinavian caucasians. Epidemiological studies have implicated a genetic component to psoriasis. In the past 12 years multiple genome-wide linkage analyses have identified putative susceptibility loci on several chromosomes, with a major locus in the major histocompatibility complex region. OBJECTIVES: To investigate the genetic basis of familial psoriasis in the Tunisian population using a genome-wide linkage scan in seven ultiplex psoriatic families from Tunisia. METHODS: Following single nucleotide polymorphism (SNP) genotyping on the Affymetrix 10K SNP array, we performed nonparametric linkage (NPL) multipoint analyses to identify genotypes and obtain evidence for linkage with psoriasis across the genome. RESULTS: No chromosomal region gave consistent evidence for linkage, providing evidence for genetic heterogeneity in Tunisian psoriasis families. Significant evidence for linkage of psoriasis to chromosome 2p12 was seen in one family. We also identified several regions of tentative psoriasis linkage on chromosomes 2q, 4q, 6p, 11q, 12q, 9q and 13q. One family exhibiting suggestive evidence for linkage to 17q25 (PSORS2) was identified and all affected members harboured a p.Gly117Ser mutation in CARD14 (caspase recruitment domain family, member 14), recently reported to lead to psoriasis in a large family from the U.S.A. CONCLUSIONS: Our results support the genetic heterogeneity of psoriasis in the Tunisian population, provide confirmatory evidence for a novel psoriasis locus at chromosome 2p12 and reveal a psoriasis family with a mutation at PSORS2.

D4 receptor deficiency in mice has limited effects on impulsivity and novelty seeking.

Alleles of the human dopamine D(4) receptor (D(4)R) gene (DRD4.7) have repeatedly been found to correlate with novelty seeking, substance abuse, pathological gambling, and attention-deficit hyperactivity disorder (ADHD). If these various psychopathologies are a result of attenuated D(4)R-mediated signaling, mice lacking D(4)Rs (D(4)KO) should be more impulsive than wild-type (WT) mice and exhibit more novelty seeking. However, in our study, D(4)KO and WT mice showed similar levels of impulsivity as measured by delay discounting performance and response inhibition on a Go/No-go test, suggesting that D(4)R-mediated signaling may not affect impulsivity. D(4)KO mice were more active than WT mice in the first 5 min of a novel open field test, suggesting greater novelty seeking. For both genotypes, more impulsive mice habituated less in the novel open field. These data suggest that the absence of D(4)Rs is not sufficient to cause psychopathologies associated with heightened impulsivity and novelty seeking.

Magnetic resonance imaging of the shoulder: a review of potential sources of diagnostic errors.

Shoulder magnetic resonance (MR) imaging and MR arthrography are frequently utilized in the evaluation of shoulder pain and instability. The clinical scenario and imaging findings may be confusing to clinicians and radiologists and may present diagnostic challenges for those involved in evaluating and treating shoulder pathology. Often rotator cuff and labral abnormalities may be coexistent, clinical manifestations of denervation syndromes may be confusing to clinicians, and normal anatomic variations, imaging pitfalls, and various artifacts may cause dilemmas for the radiologist. This article will review the most frequently encountered mimickers and pitfalls of MR imaging of the shoulder.

Vaccines, biological warfare, and bioterrorism.

This article presents a brief history of the use of biological agents in warfare and bioterrorism. Bacillus anthracis, smallpox virus, and Yersinia pestis, historically have been and currently are considered the most likely candidates for potential use under these circumstances. This article discusses the clinical syndromes these agents cause and the role of vaccines in protection against them.

Cost-effectiveness of immediate MR imaging versus traditional follow-up for revealing radiographically occult scaphoid fractures.

OBJECTIVE: For suspected scaphoid fractures with no radiographic evidence of fracture, treating symptoms with immobilization and radiographic follow-up has long been the standard of care. Modified MR imaging of the wrist is offered at our institution in screening for radiographically occult scaphoid fractures at the time of initial presentation to the emergency department. We show the advantages and comparative costs of this modified protocol versus a traditional protocol. MATERIALS AND METHODS: Our modified protocol consists of coronal thin-section T1-weighted and fast spin-echo T2-weighted MR images with fat saturation. A review of the literature was performed to assess the accuracy of clinical examination, radiography, and other modalities in the evaluation of scaphoid fractures of the wrist. Charges for this procedure are compared with charges for traditional follow-up. RESULTS: Three of four patients with positive results at clinical examination and negative findings on initial radiographs will be needlessly immobilized and monitored. The charges to the patient at our institution for screening MR imaging of the wrist are $770. The total charges to the patient with the traditional protocol, which would not be necessary with screening MR imaging, are $677 or more if a diagnosis is not made at this time. Bone scanning or routine MR imaging is often eventually used. CONCLUSION: Cost analysis at our institution suggests the two protocols are nearly equivalent from a financial standpoint. The loss of productivity for patients who are unnecessarily in casts or splints may be substantial. Screening MR imaging of the wrist in this setting is becoming accepted at our institution in a manner similar to screening MR imaging of the hip.

MR imaging of meniscal contusion in the knee.

OBJECTIVE: We describe focal abnormal signal of the meniscus in the knees of six patients who had a history of acute trauma to the knee. This signal abuts the articular surface of the meniscus on MR imaging but does not meet criteria for a meniscal tear or degeneration. CONCLUSION: Acute trauma to the knee may cause an abnormal signal in the meniscus that does not meet the previously described criteria for a meniscal tear or an intrasubstance degeneration. This abnormal signal could be misinterpreted as a tear because of its contact with the articular surface; this signal is seen most often in our series in the setting of an anterior cruciate ligament tear with adjacent bone contusions. We suggest that this signal may be due to a contusion of the meniscus and that the signal may resolve over time in some patients.

Bony ankylosis following thermal and electrical injury.

OBJECTIVE: Bony ankylosis has been described following trauma, paralysis, psoriasis, Reiter's syndrome, ankylosing spondylitis, juvenile chronic arthritis and rheumatoid arthritis. Reports of bony ankylosis following thermal and electrical injury are limited. DESIGN AND PATIENTS: Thirteen cases of burn-related joint ankylosis in four patients are presented. CONCLUSION: Patients with burns from thermal or electrical injury may develop bony ankylosis among other radiographic manifestations. This bony ankylosis may result either from bridging extra-articular heterotopic ossification with preservation of the underlying joint or from intra-articular fusion due to joint destruction.

Discoid lateral meniscus and the frequency of meniscal tears.

OBJECTIVE: To use MRI to determine the incidence of discoid lateral menisci in a large study population, and to compare those patients with those without a discoid meniscus in order to assess the impact of a discoid lateral meniscus on the frequency of meniscal tears. DESIGN AND PATIENTS: Results of 1,250 knee MRI studies were retrospectively reviewed. Using the criterion of three or more meniscal body segments on sequential sagittal images, 56 patients were found to have a discoid lateral meniscus. After exclusion of patients with prior knee surgery, 49 patients with a discoid lateral meniscus were compared with 1,146 patients without a discoid meniscus. Patients were categorized as having tears of the medial meniscus, lateral meniscus, or both menisci. RESULTS: In our study population, there was a 4.5% incidence of discoid lateral meniscus. Seventy-one percent of patients with a discoid lateral meniscus had one or more meniscal tears, compared with 54% of the comparison group (P=0.01). The frequency of solitary lateral meniscal tears in the discoid group was also higher than in the comparison group: 20%.versus 11% (P=0.03). The frequency of solitary medial meniscal tears and concomitant tears of both menisci were not significantly different between the two groups. CONCLUSIONS: The discoid lateral meniscus is an uncommon variant, but not as rare as once believed. Compared with the normal semilunar meniscus, the discoid lateral meniscus has a higher frequency of meniscal tears, and solitary tears of the lateral meniscus are more common in the discoid variant. The frequency of medial meniscal tears is not altered by the presence of a discoid lateral meniscus.

Association of posterior tibial tendon injury with spring ligament injury, sinus tarsi abnormality, and plantar fasciitis on MR imaging.

OBJECTIVE: The purpose of this study was to investigate the frequency of abnormalities of the spring ligament, sinus tarsi, and plantar fascia revealed on MR imaging in a group of patients with advanced injury of the posterior tibial tendon. MATERIALS AND METHODS; MR images from 25 patients with advanced posterior tibial tendon injury were retrospectively examined for spring ligament, sinus tarsi, and plantar fascia abnormalities. These images were randomly compared with those obtained from 25 control patients with normal-appearing posterior tibial tendons. RESULTS: The spring ligament was abnormal in 23 (92%) of 25 patients with a posterior tibial tendon injury and seven (28%) of 25 patients with a normal posterior tibial tendon (p < 0.0001). The sinus tarsi was abnormal in 18 (72%) of 25 patients with posterior tibial tendon injury and nine (36%) of 25 patients with a normal posterior tibial tendon (p < 0.0132). The plantar fascia was abnormal in seven (32%) of 22 patients with posterior tibial tendon injury and two (9%) of 22 patients with a normal posterior tibial tendon (p < 0.0768). Two or more associated abnormalities were present in 20 (80%) of 25 patients with posterior tibial tendon injury and four (16%) of 25 patients with a normal posterior tibial tendon (p < 0.0001). CONCLUSION: Advanced posterior tibial tendon injury has a high association with spring ligament and sinus tarsi abnormalities on MR imaging. There was a low association between advanced posterior tibial tendon injury and plantar fascia abnormality. Patients with posterior tibial tendon injury often have abnormalities of two or more associated structures.

Focal articular cartilage lesions of the superior humeral head: MR imaging findings in seven patients.

OBJECTIVE: We describe the MR imaging findings of focal articular cartilage lesions of the superior humeral head and the clinical features in seven patients. CONCLUSION: Focal articular cartilage lesions of the superior humeral head are rare lesions that may cause clinical symptoms and may be easily overlooked on MR imaging. These lesions occur in a particular location (along the superior surface of the posterior humeral head, medial to the expected location of a Hill-Sachs lesion), are caused by trauma, and do not seem to have a specific mechanism of injury. Because of improvements in MR imaging of cartilage, this area of the shoulder should be inspected for this lesion.

JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome.

X-linked autoimmunity-allergic disregulation syndrome (XLAAD) is an X-linked recessive immunological disorder characterized by multisystem autoimmunity, particularly early-onset type 1 diabetes mellitus, associated with manifestations of severe atopy including eczema, food allergy, and eosinophilic inflammation. Consistent with the allergic phenotype, analysis of two kindreds with XLAAD revealed marked skewing of patient T lymphocytes toward the Th2 phenotype. Using a positional-candidate approach, we have identified in both kindreds mutations in JM2, a gene on Xp11.23 that encodes a fork head domain-containing protein. One point mutation at a splice junction site results in transcripts that encode a truncated protein lacking the fork head homology domain. The other mutation involves an in-frame, 3-bp deletion that is predicted to impair the function of a leucine zipper dimerization domain. Our results point to a critical role for JM2 in self tolerance and Th cell differentiation.

The relationship of age, gender, and degenerative changes observed on radiographs of the shoulder in asymptomatic individuals.

Radiographs of the shoulders of 84 asymptomatic individuals aged between 40 and 83 years were evaluated to determine changes in 23 specific areas. Two fellowship-trained orthopaedic radiologists graded each area on a scale of 0 to II (normal 0, mild changes I, advanced changes II). Logistic regression analysis indicated age to be a significant predictor of change (p < 0.05) for sclerosis of the medial acromion and lateral clavicle, the presence of subchondral cysts in the acromion, formation of osteophytes at the inferior acromion and clavicle, and narrowing and degeneration of the acromioclavicular joint. Gender was not a significant predictor (p > 0.05) for radiological changes. Student's t-test determined significance (p < 0.05) between age and the presence of medial acromial and lateral clavicular sclerosis, subchondral acromial cysts, inferior acromial and clavicular osteophytes, and degeneration of the acromioclavicular joint. Radiological analysis in conditions such as subacromial impingement, pathology of the rotator cuff, and acromioclavicular degeneration should be interpreted in the context of the symptoms and normal age-related changes.

The MR imaging appearance of longitudinal split tears of the peroneus brevis tendon.

PURPOSE: Longitudinal split tears of the peroneus brevis tendon have been increasingly reported as a source of lateral ankle pain and disability. MR imaging is useful in identifying the appearance of longitudinal split tears of the peroneus brevis tendon to differentiate this entity from other causes of chronic lateral ankle pain. We observed variations in anatomy associated with these tears. MATERIALS AND METHODS: Twenty-two patients (eleven males, eleven females) were identified as having longitudinal split tears of the peroneus brevis tendon. These cases were reviewed retrospectively to evaluate for the following: shape of the peroneus brevis tendon, high signal in the peroneus brevis tendon, tendon subluxation, appearance of the superior peroneal retinaculum, presence of osseous changes in the ankle, lateral ankle ligaments, presence of a bony fibular spur, flattening of the peroneal groove of the fibula and presence of a peroneus quartus. A control group consisted of twenty ankles imaged for reasons other than lateral ankle pain. The same structures were assessed in this group. A Fisher's exact P-value was used to determine the significance of each finding in the two groups. RESULTS: Statistically significant associated findings were chevron shaped tendon (p = .0001), high signal in the peroneus brevis (p = .0017), bony changes (p = .0001), flat peroneal groove (p = .0001), abnormal lateral ligaments (p = .0004), and lateral fibular spur (p = .0006). CONCLUSIONS: MR imaging is useful in differentiating longitudinal split tears of the peroneus brevis tendon from other lateral ankle disorders. It can show the extent of the abnormality in the tendon and the associated findings of soft tissue and/or bone variations which must be addressed at the time of surgery.

The "mini brain": plasmacytoma in a vertebral body on MR imaging.

OBJECTIVE: Patients with solitary plasmacytoma in the spine frequently require a biopsy for diagnosis of their condition. We report an appearance of plasmacytoma in the spine, which is sufficiently pathognomonic to obviate biopsy. CONCLUSION: Identification of a "mini brain" in an expansile lesion in the spine is characteristic of plasmacytoma. It is important that radiologists note this characteristic because biopsy can be avoided in patients with this appearance. Although biopsy might still be required at many institutions, at our institution, surgeons find this appearance sufficiently pathognomonic to bypass biopsy and start treatment.