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Extrinsic factors including solar radiation and air pollution significantly impact facial skin aging. The efficacy and tolerability of a 2-step skincare regimen consisting of a vitamin C antioxidant serum (VCAS) and a 100% mineral tinted sunscreen moisturizer (TSM) were evaluated in women with hyperpigmented and photodamaged facial skin exposed to beach, mountain, and river-traversed basin city stressors.This was an institutional review board (IRB)-approved, multi-center, prospective, open-label study involving healthy subjects. Thirty-six females aged 35 to 60 years with Fitzpatrick Skin Types I to V and exhibiting moderate to severe hyperpigmentation and moderate photodamage were recruited. The VCAS was applied to the global face twice-daily (morning and evening), and the TSM was applied in the morning with at least 2 reapplications during daily activity for 12 weeks. Clinical grading with a validated scale, standardized photography, and a self-assessment questionnaire were performed at baseline and weeks 4, 8, and 12.Statistically significant improvements were shown in clinically graded efficacy parameters at weeks 4, 8, and 12. Subjects showed an average improvement of 11.7%, 14.9%, and 19.1% in overall photodamage and an average improvement of 19.5%, 23.4%, and 24.5% in clarity/brightness at weeks 4, 8, and 12, respectively. Forehead lines and cheek lines demonstrated clinically significant improvement from baseline to week 12. Both products were well-tolerated and well-perceived by subjects.The 2-step skincare regimen was well-tolerated and effective in improving extrinsic signs of facial aging induced by solar radiation and air pollution stressors after 12 weeks of use. J Drugs Dermatol. 2023;22(1):16-22. doi:10.36849/JDD.7154.

Taylor's law is a widely observed empirical pattern that relates the variances to the means of population densities. We present four extensions of the classical Taylor's law (TL): (1) a cubic extension of the linear TL describes the mean–variance relationship of human mortality at subnational levels well; (2) in a time series, long-run variance measures not only variance but also autocovariance, and it is a more suitable measure than variance alone to capture temporal/spatial correlation; (3) an extension of the classical equally weighted spatial variance takes account of synchrony and proximity; (4) robust linear regression estimators of TL parameters reduce vulnerability to outliers. Applying the proposed methods to age-specific Japanese subnational death rates from 1975 to 2018, we study temporal and spatial variations, compare different coefficient estimators, and interpret the implications. We apply a clustering algorithm to the estimated TL coefficients and find that cluster memberships are strongly related to prefectural gross domestic product. The time series of spatial TL coefficients has a decreasing trend that confirms the narrowing gap between rural and urban mortality in Japan.

Aging is a multifactorial response to genetic preprogramming nuances, sun exposure, and ultraviolet radiation. Recently, there has been a paradigm shift toward minimally invasive rejuvenation.This prospective multicenter study aims to evaluate the efficacy and safety of a novel hands-free bipolar bulk radiofrequency (RF) device in terms of improvement in skin appearance.This multicenter prospective study enrolled subjects aged 35 to 75 years with visible signs of aging. The primary objective was to evaluate skin appearance pretreatment and at 1, 3, and 6 months after the final treatment. Each patient received 3 total treatments to the chin and cheeks using the hands-free RF device spaced 2 weeks apart.In total, data from 87 patients were assessed from 6 treatment sites. The average age was 54 years (range 35-75 years). Most patients were female (97%), and Fitzpatrick skin types I to V were represented. Overall, patients found the procedures to be relatively pain-free, and both patients and investigators felt they noted some improvement in their skin appearance. Histological sections demonstrated an increase in collagen or elastic fibers within the papillary dermis.This study supports the use of this novel noninvasive hands-free bipolar facial remodeling device for the improvement of skin appearance.

A cosmeceutical topical formulation containing a non-hormonal estrogen receptor activator, Methyl Estradiolpropanoate (MEP), has been developed to address periorbital skin aging in post-menopausal women with estrogen-deficient skin (EDS).The primary objective of the study was to evaluate the efficacy of Emepelle Eye Creamreg; (Biopelle, Ferndale Pharma Group, Ferndale, MI, USA) for the rejuvenation of the periorbital skin areas in women EDS. The secondary objectives were to assess the tolerability and satisfaction with Emepelle Eye Cream as assessed by the clinical investigator and the participants.Clinical improvement (ie, change from baseline visit) to the end of study topical application in the periorbital areas were assessed by the clinical investigator using the clinician-rated quality of periorbital skin area visual scoring scale and by the participant using the participantrsquo;s self-evaluation of the quality of periorbital skin area questionnaire. Secondary objectives and endpoints were assessed using a subject Quality of Life (QoL) evaluation, a clinician- and a participant-evaluation of tolerability and side effects, and the C-GAIS and P-GAIS questionnaires. Baseline scores were compared to scores at the follow-up visits.Clinician evaluations included a Global Aesthetic Improvement Scale (GAIS) rating of periorbital skin areas using a 6-point rating scale as well as tolerability and side effects. The averaged clinical GAIS improvement for all subjects who completed the study improved by 21%. The mean clinician GAIS score at study completion was 2.7, and 26 of the 31 subjects who completed the study showed improvement. A clinician GAIS score of 1 (very much improved) was observed in 3 study subjects. The averaged subject improvement results included improvements in each category at the primary endpoint. The subjects reported that their satisfaction with their periorbital appearance improved by 47% as compared to before treatment. The product was well tolerated by all subjects and no significant side effects were reported.In an open label study of 31 female subjects who had been amenorrheic for at least one year, topical application of Emepelle Eye Cream for periorbital skin rejuvenation was effective and well-tolerated. J Drugs Dermatol. 2022;21(11):1185-1190. doi:10.36849/JDD.7279.

Atopic dermatitis (AD) in liver transplant (LT) recipients is well-documented, despite frequent use of immunosuppressants in these patients. In a liver transplant population, the prevalence of AD in children and adults is 27.6% and 10.3%, respectively.1 However, there is dearth ofliterature regardingtreatment of this population, and standard regimens are not well-defined.2-4 Here, we report a case of successful treatment of AD in an orthotopic LT patient with dupilumab.

Understanding the mechanisms underlying species divergence remains a central goal in evolutionary biology. Landscape genetics can be a powerful tool for examining evolutionary processes. We used genome-wide scans to genotype samples from populations of eight Angophora species. Angophora is a small genus within the eucalypts comprising common and rare species in a heterogeneous landscape, making it an appropriate group to study speciation. We found A. hispida was highly differentiated from the other species. Two subspecies of A. costata (subsp. costata and subsp. euryphylla) formed a group, while the third (subsp. leiocarpa, which is only distinguished by its smooth fruits and provenance) was supported as a distinct pseudocryptic species. Other species that are morphologically distinct could not be genetically differentiated (e.g., A. floribunda and A. subvelutina). Distribution and genetic differentiation within Angophora were strongly influenced by temperature and humidity, as well as biogeographic barriers, particularly rivers and higher elevation regions. While extensive introgression was found between many populations of some species (e.g., A. bakeri and A. floribunda), others only hybridized at certain locations. Overall, our findings suggest multiple mechanisms drove evolutionary diversification in Angophora and highlight how genome-wide analyses of related species in a diverse landscape can provide insights into speciation.

Enriching our scientific understanding of the biological world has been a major contribution of naturalists. However, while contributions from individuals such as Charles Darwin are both well-known and taught, those of female naturalists remain relatively unknown and have not entered curriculum. This absence means fewer options available to teachers which could address an increasingly diverse student population. Confounding this gap is the time and resources allotted by secondary schools for molecular biology and medically-oriented labs which are useful, but not always essential for natural history or biodiversity studies. Given this background, this paper suggests that funds and support be divided between DNA labs and a movement towards “environmental-science era” enrichment. This would allow classes to incorporate personalities, lessons, and observations of key naturalists and natural histories. Thus, teaching the how and why of Darwin’s becoming a naturalist, followed by stories of female naturalists responds to diversification of the student body and more directly matching curriculum to pressing national needs. Thus, prior to making their conclusions, students have been exposed to what is termed here “teaching developmentally,” so that they can see how these individuals became scientists. biodiversity, totaling over 800 citations, and continues to work for various educational services as an instructor or director.

Ecological restoration requires balancing levels of genetic diversity to achieve present-day establishment as well as long-term sustainability. Assumptions based on distributional, taxonomic or functional generalizations are often made when deciding how to source plant material for restoration. We investigate this assumption and ask whether species-specific data is required to optimize provenancing strategies. We use population genetic and environmental data from five congeneric and largely co-distributed species of Acacia to specifically ask how different species-specific genetic provenancing strategies are based on empirical data and how well a simple, standardized collection strategy would work when applied to the same species. We find substantial variability in terms of patterns of genetic diversity and differentiation across the landscape among these five co-distributed Acacia species. This variation translates into substantial differences in genetic provenancing recommendations among species (ranging from 100% to less than 1% of observed genetic variation across species) that could not have been accurately predicted a priori based on simple observation or overall distributional patterns. Furthermore, when a common provenancing strategy was applied to each species, the recommended collection areas and the evolutionary representativeness of such artificially standardized areas were substantially different (smaller) from those identified based on environmental and genetic data. We recommend the implementation of the increasingly accessible array of evolutionary-based methodologies and information to optimize restoration efforts.

BACKGROUND Obesity has been associated with attenuated vaccine responses and an increased risk of contracting pneumococcal pneumonia, but no study to our knowledge has assessed the impact of obesity and genetics on 23-valent pneumococcal vaccine (PPSV23) efficacy. We assessed the relationship of obesity (primary analysis) and stimulator of interferon genes (STING1) genotype (secondary analysis) on PPSV23 efficacy. METHODS Nonobese (BMI 22–25 kg/m2) and obese participants (BMI ≥30 kg/m2) were given a single dose of PPSV23. Blood was drawn immediately prior to and 4–6 weeks after vaccination. Serum samples were used to assess PPSV23-specific antibodies. STING1 genotypes were identified using PCR on DNA extracted from peripheral blood samples. RESULTS Forty-six participants were categorized as nonobese (n = 23; 56.5% women; mean BMI 23.3 kg/m2) or obese (n = 23; 65.2% women; mean BMI 36.3 kg/m2). Obese participants had an elevated fold change in vaccine-specific responses compared with nonobese participants (P < 0.0001). The WT STING1 group (R232/R232) had a significantly higher PPSV23 response than individuals with a single copy of HAQ-STING1 regardless of BMI (P = 0.0025). When WT was assessed alone, obese participants had a higher fold serotype-specific response compared with nonobese participants (P < 0.0001), but no difference was observed between obese and nonobese individuals with 1 HAQ allele (P = 0.693). CONCLUSIONS These observations demonstrate a positive association between obesity and PPSV23 efficacy specifically in participants with the WT STING1 genotype. TRIAL REGISTRATION ClinicalTrials.gov NCT02471014. FUNDING This research was supported by the NIH and the University of Florida MD-PhD Training Program., Obesity and a WT STING1 genotype are positively associated with efficacy of the 23-valent pneumococcal vaccine in a small cohort of subjects.

Premise of the Study: Nuclear microsatellite markers were developed for population genetic analysis of the threatened paleoendemic conifer Pherosphaera hookeriana (Podocarpaceae). Methods and Results: Fifteen variable loci were identified showing one to 13 alleles per population, with seven loci displaying at least four alleles in all populations, and the average number of alleles per locus ranging from 4.80 to 5.93 per population. Levels of observed heterozygosity per locus varied from 0.00 to 0.91, while average heterozygosity across all loci varied from 0.54 to 0.63 between populations. All loci also amplified in the endangered congener P. fitzgeraldii, but only five of the loci had more than one allele. Conclusions: These 15 loci are the first microsatellite markers developed in the genus Pherosphaera. These loci will be useful for investigating the species' extant genetic diversity and structure, the impact of past environmental change, and the significance of asexual reproduction.

Systemic lupus erythematosus is an autoimmune disease characterized by autoantibodies and systemic inflammation that results in part from dendritic cell activation by nucleic acid containing immune complexes. There are many mouse models of lupus, some spontaneous and some induced. We have been interested in an induced model in which estrogen is the trigger for development of a lupus-like serology. The R4A transgenic mouse expresses a transgene-encoded H chain of an anti-DNA Ab. This mouse maintains normal B cell tolerance with deletion of high-affinity DNA-reactive B cells and maturation to immunocompetence of B cells making nonglomerulotropic, low-affinity DNA-reactive Abs. When this mouse is given estradiol, normal tolerance mechanisms are altered; high-affinity DNA-reactive B cells mature to a marginal zone phenotype, and the mice are induced to make high titers of anti-DNA Abs. We now show that estradiol administration also leads to systemic inflammation with increased B cell-activating factor and IFN levels and induction of an IFN signature. DNA must be accessible to B cells for both the production of high-affinity anti-DNA Abs and the generation of the proinflammatory milieu. When DNase is delivered to the mice at the same time as estradiol, there is no evidence for an abrogation of tolerance, no increased B cell-activating factor and IFN, and no IFN signature. Thus, the presence of autoantigen is required for positive selection of autoreactive B cells and for the subsequent positive feedback loop that occurs secondary to dendritic cell activation by DNA-containing immune complexes.

International Journal of Paediatric Dentistry 2010; 20: 179–185 Objectives. This study examined caries level, amount of calculus, and oral microbial environment in gastrostomy tube (GT)-fed children compared with healthy children and children with disabilities orally fed (PO). Study design. The study group consisted of 12 GT-fed children and the two control groups consisted of 16 children with disabilities orally fed and 17 healthy children. DMF-T/dmf-t index, calculus index, Mutans Streptococci (MS), Lactobacilli (LB) levels and salivary buffer capacity were examined. Results. DMF-T/dmf-t index was significantly lower in the tube-fed group. Calculus index was highest in the tube-fed group. MS and LB levels were the lowest in the tube-fed children. Correlation was found between MS and DMF-T/dmf-t. Conclusions. Tube-fed children demonstrated significantly higher calculus levels and less caries, MS, and LB levels then healthy children or children with disabilities eating PO.

N-glycans of human Fcgamma receptor III (FcgammaR III) are believed to be involved in the interaction with complement receptor type 3 (CR3) (Sehgal et al. [1993] J. Immunol., 150, 4571-4580). Recombinant human soluble FcgammaRIII (rhsFcgammaRIII), which is produced in baby hamster kidney (BHK) cells, has been shown to interact with CR3 in a manner similar to native FcgammaRIII. We elucidated the N-glycosylation profiles of rhsFcgammaRIII by the 3D high-performance liquid chromatography mapping technique. It was revealed that the N-glycans of rhsFcgammaRIII are much more divergent (consisting of 20 neutral, 7 monosialyl, 4 disialyl, 5 trisialyl, and 1 tetrasialyl oligosaccharides) than those previously determined for BHK-expressed mouse sFcgammaRII, notwithstanding close structural similarity of polypeptide chains between the two sFcgammaRs. Particularly, high-mannose type oligosaccharides are specifically expressed on rhsFcgammaRIII.

PURPOSE: To summarize evidence on the costs of treating patients in clinical trials and to describe the Cost of Cancer Treatment Study, an ongoing effort to produce generalizable estimates of the incremental costs of government-sponsored cancer trials. METHODS: A retrospective study of costs will be conducted with 1,500 cancer patients recruited from a randomly selected sample of institutions in the United States. Patients accrued to either phase II or phase III National Cancer Institute–sponsored clinical trials during a 15-month period will be asked to participate in a study of their health care utilization (n = 750). Costs will be measured approximately 1 year after their trial enrollment from a combination of billing records, medical records, and an in-person survey questionnaire. Similar data will be collected for a comparable group of cancer patients not in trials (n = 750) to provide an estimate of the incremental cost. RESULTS: Evidence suggests insurers limit access to trials because of cost concerns. Public and private efforts are underway to change these policies, but their permanent status is unclear. Previous studies found that treatment costs in clinical trials are similar to costs of standard therapy. However, it is difficult to generalize from these studies because of the unique practice settings, insufficient sample sizes, and the exclusion of potentially important costs. CONCLUSION: Denials of coverage for treatment in a clinical trial limit patient access to trials and could impede clinical research. Preliminary estimates suggest changes to these policies would not be expensive, but these results are not generalizable. The Cost of Cancer Treatment Study is an ongoing effort to provide generalizable estimates of the incremental treatment cost of phase II and phase III cancer trials. The results should be of great interest to insurers and the research community as they consider permanent ways to finance cancer trials.

To categorize national medical expenditures into patient-centered categories.The 2007 Medical Expenditure Panel Survey (MEPS), a nationally representative annual survey of the civilian noninstitutionalized population.Descriptive statistics categorizing expenditures into seven patient-centered care categories: chronic conditions, acute illness, trauma/injury or poisoning, dental, pregnancy/birth-related, routine preventative health care, and other.MEPS cohort.Nearly half of expenditures were for chronic conditions. The remaining expenditures were as follows: acute illness (25 percent), trauma/poisoning (8 percent), dental (7 percent), routine preventative health care (6 percent), pregnancy/birth-related (4 percent), and other (3 percent). Hospital-based expenditures accounted for the majority for acute illness, trauma/injury, and pregnancy/birth and over a third for chronic conditions.This patient-centered viewpoint may complement other methods to examine health care expenditures and may better represent how patients interact with the health care system and expend resources.

R4A is an anti-DNA antibody derived by hybridomas technology from a BALB/c mouse. The study of its properties has helped to elucidate aspects of the physiopathology of Systemic Lupus Erythematosus (SLE). It has been useful to decipher the mechanisms implicated in breaks in B cell self tolerance by B cell extrinsic or B cell intrinsic factors. Furthermore, it illustrates the importance of molecular mimicry in understanding the cellular and molecular effects relevant to some manifestations of neuropsychiatric lupus, as it cross-reacts with the D/E W D/E YS/G peptide sequence present in subunits of the N-methyl D-aspartate receptor (NMDAR).

In many hospitals a routine chest X-ray is performed on admission. There are, however, scant data regarding its usefulness in contemporary patient populations.We studied consecutive patients admitted during a 2 month period to a single department of medicine, where hospital policy mandates performing an admission CXR. Two senior clinicians not involved in the care of these patients assessed the discharge summaries for a clinical indication to perform CXR on admission, as well as its contribution to patient management (major positive, major negative, minor positive, or no contribution).There were 675 patients whose mean age was 64.5 +/- 17.2 years. In 19.6% (130 cases) CXR was not performed. Of the 545 CXRs done, 260 (48%) were normal. In only 128 (23.5%) did the admission CXR make a major positive contribution to diagnosis or treatment. In 61 (11.2%) it provided a minor positive contribution and in 153 (28.1%) a major negative contribution. In 184 patients (33.8%) the CXR did not affect either diagnosis or management. It made a major positive contribution to management in patients for whom there was an indication for performing the X-ray (odds ratio 10.3, P0.0005) and in those with a relevant finding on physical examination (OR 1.63, P = 0.110). For the 329 patients who had neither a clinical indication for performing a CXR nor an abnormal chest examination the admission CXR contributed to patient management in only 12 cases (3.6%).A routine admission CXR has a significant impact on patient management only in those patients in whom there are relevant findings on physical examination or a clear clinical indication for performing the test. There is no need to routinely order CXR on admission to hospital.

A crucial prerequisite for a commercial success of large-scale CPV is the capability for mass production of the manufacturing processes. For the optical components (primary and secondary lenses) there do exist various production concepts with different potential for cost efficient mass production. The most promising concept is (compression) injection molding, a process technology for optical components already proven in mature industries like Automotive or Semiconductor. While the capability of the injection molding process for a real mass production is already well established, it needs to be proven that also the high quality requirements in CPV can be met. Injection molded PMMA Fresnel lenses can be manufactured with peak-to-valley deviations less than 10 µm, showing nearly no inner stress and very low and homogeneous edge radii in the order of 5 µm.

Our research, inspired by the pioneering works of Isaac Witz in the 1980s, established that 40% of human metastatic melanomas express ectopically inhibitory Fc gamma receptors (FcgammaRIIB), while they are detected on less than 5% of primary cutaneous melanoma and not on melanocytes. We demonstrated that these tumoral FcgammaRIIB act as decoy receptors that bind the Fc portion of antimelanoma IgG, which may prevent Fc recognition by the effector cells of the immune system and allow the metastatic melanoma to escape the humoral/natural immune response. The FcgammaRIIB is able to inhibit the ADCC (antibody dependent cell cytotoxicity) in vitro. Interestingly, the percentage of melanoma expressing the FcgammaRIIB is high (70%) in organs like the liver, which is rich in patrolling NK (natural killer) cells that exercise their antitumoral activity by ADCC. We found that this tumoral FcgammaRIIB is fully functional and that its inhibitory potential can be triggered depending on the specificity of the anti-tumor antibody with which it interacts. Together these observations elucidate how metastatic melanomas interact with and potentially evade humoral immunity and provide direction for the improvement of anti-melanoma monoclonal antibody therapy.

Crucial for the performance and longevity of CPV installations is the efficiency of the optics used. Low production cost and high performance are key for the economical success of a CPV concept. To be able to compete with existing energy sources, proven mass production methods as well as high performance materials have to be employed. The injection molding process is the ideal serial production process capable to deliver at the same time high part quantities, excellent part precision and repeatable part quality at low manufacturing cost. Primary and secondary optics require different materials to be applied. The Pros and Cons of these materials in terms of production properties and achievable part precision will be discussed. We will show quality results for primary Fresnel optics using PMMA and, alternatively Silicone on Glass. For secondary optics we will demonstrate the use of optical silicone lenses widely used for high power LED applications today. Optical grade silicone has an excellent environmenta...

A 65-year-old woman who had type 2 diabetes mellitus, hypertension and coronary artery disease was admitted with a 4-day history of pain, erythema and swelling of her left toes and adjacent dorsum of her foot associated with high temperature. Pulses were normal and no peripheral neuropathy was found. Bullous erysipelas was diagnosed (Fig. 1). The ESR was 118 mm/h; CRP 54 mg/dl and WBC 10 £ 10/ l with a left shift. Oral antibiotics (clindamycin + oXoxacin) were commenced. At night, she was given a 500 mg dipyrone tablet for leg pain. Three days later a palpable purpuric rash appeared below the knee on her right leg alone (Fig. 1). Biopsy revealed changes characteristic of leukocytoclastic vasculitis (not shown). Mild arthralgia was the only other change observed. Once she improved suYciently at home and started walking, she presented again to the emergency room, alarmed because multiple additional typical lesions now developed on the other leg as well. Bulla formation occurs in about 5% of patients with erysipelas and require longer treatment [1]. The patient’s hypersensitivity vasculitis was most likely associated with the administration of dipyrone: drug therapy is the most common precipitating event in patients with this type of vasculitis [2], no other cause could be identiWed and the purpuric rash later receded spontaneously despite continued antibiotic treatment. The eruption of small vessel vasculitis occurs predominantly in dependent areas such as the lower extremities, below the knees and is characteristically symmetrical [3, 4]. The unilateral development of leukocytoclastic vasculitis in one leg is odd and unexpected. Our explanation is that before the appearance of vasculitis, the infected leg was kept horizontal either in bed or on a chair for most of the day. Once she started walking, lesions developed symmetrically. Thus, increased hydrostatic pressure must have a greater role in the pathogenesis of the immune-mediated purpuric lesions of leukocytoclastic vasculitis than we usually believe.

A 69-year-old man presented with fever and chills of acute onset without any localizing complaints. He was previously generally well, but had a history of dyslipidemia and benign prostatic hypertrophy. The findings of his examination and laboratory tests were normal, and he was discharged. He was

FcgammaRs are a family of heterogeneous molecules that play opposite roles in immune response and control the effector functions of IgG antibodies. In many cancers, IgG antibodies are produced that recognize cancer cells, form immune complexes and therefore, activate FcgammaR. The therapeutic efficacy of monoclonal IgG antibodies against hematopoietic and epithelial tumors also argue for an important role of IgG antibodies in anti-tumor defenses. Since the 1980s, a series of lines of evidence in experimental models and in humans strongly suggest that FcgammaR are involved in the therapeutic activity of monoclonal IgG antibodies by activating the cytotoxic activity of FcgammaR-positive cells such as NK cells, monocytes, macrophages and neutrophils and by increasing antigen presentation by dendritic cells. Since many cell types co-express activating and inhibitory FcgammaR, the FcgammaR-dependent effector functions of IgG anti-tumor antibodies are counterbalanced by the inhibitory FcgammaRIIB. In addition, some tumor cells express FcgammaR either constitutively, such as B cell lymphomas or ectopically, such as 40% of human metastatic melanoma. The tumor FcgammaR isoform is preferentially FcgammaRIIB, which is functional at least in human metastatic melanoma. This review summarizes these data and discusses how FcgammaRIIB expression may influence the anti-tumor immune reaction and how beneficial or deleterious this expression could be for the efficiency of therapeutics based on monoclonal anti-tumor antibodies.

Classic immunologic teaching describes the brain as an immunologically privileged site. Studies of neuroimmunology have focused for many years almost exclusively on multiple sclerosis, a disease in which inflammatory cells actually infiltrate brain tissue, and the rodent model of this disease, experimental allergic encephalitis. Over the past decade, however, increasingly, brain-reactive antibodies have been demonstrated in the serum of patients with numerous neurological diseases. The contribution these antibodies make to neuronal dysfunction has, in general, not been determined. Here, we describe recent studies showing that serum antibodies to the N-methyl-D-aspartate receptor occur frequently in patients with systemic lupus erythematosus and can cause alterations in cognition and behavior following a breach in the blood-brain barrier.

Classic immunologic teaching describes the brain as an immunologically privileged site. Studies of neuroimmunology have focused for many years almost exclusively on multiple sclerosis, a disease in which inflammatory cells actually infiltrate brain tissue, and the rodent model of this disease, experimental allergic encephalitis. Over the past decade, however, increasingly, brain‐reactive antibodies have been demonstrated in the serum of patients with numerous neurological diseases. The contribution these antibodies make to neuronal dysfunction has, in general, not been determined. Here, we describe recent studies showing that serum antibodies to the N‐methyl D‐asparate receptor occur frequently in patients with systemic lupus erythematosus and can cause alterations in cognition and behavior following a breach in the blood–brain barrier.

Three weeks after receiving a prosthetic aortic valve because of severe aortic stenosis, a 71-year-old man was admitted to hospital with a 3-day history of gradually increasing temperature. His temperature was 38.3οC, but the results of a physical examination were unremarkable. After 4 sets of