Perinatal Western-style diet exposure associated with decreased microglial counts throughout the arcuate nucleus of the hypothalamus in Japanese macaques.

Perinatal exposure to a high-fat, high-sugar Western-style diet (WSD) is associated with altered neural circuitry in the melanocortin system. This association may have an underlying inflammatory component, as consumption of a WSD during pregnancy can lead to an elevated inflammatory environment. Our group previously demonstrated that prenatal WSD exposure was associated with increased markers of inflammation in the placenta and fetal hypothalamus in Japanese macaques. In this follow-up study, we sought to determine whether this heightened inflammatory state persisted into the postnatal period, as prenatal exposure to inflammation has been shown to reprogram offspring immune function and long-term neuroinflammation would present a potential means for prolonged disruptions to microglia-mediated neuronal circuit formation. Neuroinflammation was approximated in 1-yr-old offspring by counting resident microglia and peripherally derived macrophages in the region of the hypothalamus examined in the fetal study, the arcuate nucleus (ARC). Microglia and macrophages were immunofluorescently stained with their shared marker, ionized calcium-binding adapter molecule 1 (Iba1), and quantified in 11 regions along the rostral-caudal axis of the ARC. A mixed-effects model revealed main effects of perinatal diet (P = 0.011) and spatial location (P = 0.003) on Iba1-stained cell count. Perinatal WSD exposure was associated with a slight decrease in the number of Iba1-stained cells, and cells were more densely located in the center of the ARC. These findings suggest that the heightened inflammatory state experienced in utero does not persist postnatally. This inflammatory response trajectory could have important implications for understanding how neurodevelopmental disorders progress.NEW & NOTEWORTHY Prenatal Western-style diet exposure is associated with increased microglial activity in utero. However, we found a potentially neuroprotective reduction in microglia count during early postnatal development. This trajectory could inform the timing of disruptions to microglia-mediated neuronal circuit formation. Additionally, this is the first study in juvenile macaques to characterize the distribution of microglia along the rostral-caudal axis of the arcuate nucleus of the hypothalamus. Nearby neuronal populations may be greater targets during inflammatory insults.

Carotenoids improve the development of cerebral cortical networks in formula-fed infant macaques.

Nutrition during the first years of life has a significant impact on brain development. This study characterized differences in brain maturation from birth to 6 months of life in infant macaques fed formulas differing in content of lutein, ß-carotene, and other carotenoids using Magnetic Resonance Imaging to measure functional connectivity. We observed differences in functional connectivity based on the interaction of diet, age and brain networks. Post hoc analysis revealed significant diet-specific differences between insular-opercular and somatomotor networks at 2 months of age, dorsal attention and somatomotor at 4 months of age, and within somatomotor and between somatomotor-visual and auditory-dorsal attention networks at 6 months of age. Overall, we found a larger divergence in connectivity from the breastfeeding group in infant macaques fed formula containing no supplemental carotenoids in comparison to those fed formula supplemented with carotenoids. These findings suggest that carotenoid formula supplementation influences functional brain development.

A systematic approach to analyse health-related quality of life in multiple sclerosis: the GEDMA study.

OBJECTIVE: To describe a holistic and comprehensive approach to the assessment of sufferer's perceptions of health-related quality of life (HRQoL) in a cohort of multiple sclerosis (MS) patients. METHODS: The GEDMA (Grupo de Enfermedades Desmielinizantes de Madrid, in Spanish) study is an ongoing longitudinal survey using quantitative and qualitative methodologies. The baseline cohort consisted of a large sample of MS patients recruited from 13 hospitals in Madrid, Spain. Using a standardized protocol we collected data concerning the sociodemographic and health status characteristics of patients, as well as implementing a modified Spanish version of the Functional Assessment of Multiple Sclerosis quality of life instrument Primary caregivers were interviewed using a specific protocol combined with the Zarit Burden Interview. RESULTS: The index cohort comprised 371 MS patients (68.7% female) of mean age 38.9+/-0.9 years. Age, sex and clinical form distribution were similar to other MS population-based surveys. There were 258 (69.5%) relapsing-remitting (RR) MS patients and 113 (30.5%) progressive MS patients. More than one-third of the married patients with progressive MS and almost a quarter of the RRMS patients separated or divorced following a diagnosis of MS; 71.3% of the progressive MS patients as well as 65.8% of the RRMS patients were unemployed as a consequence of the disease. Qualitative analysis showed that friendship and family relationships and occupational status were the most significant dimensions influenced by MS. On the other hand, the speech analysis of primary caregivers showed that emotional burden was related to patients' physical disability. Furthermore, primary caregivers described the influence of MS on their own occupational status, their nonacceptance of the disease, a perception of a lack of support by other members of the family as well as a 'selfish and intransigent' attitude of the patients themselves. CONCLUSIONS: The analysis of the GEDMA cohort provides valuable information that helps clarify the impact of MS on patients' HRQoL.

Double contrast barium enema sensitivity: a comparison of studies by radiographers and radiologists.

PURPOSE: A retrospective study of histologically proven cases of colorectal cancer (CRC) was performed to assess whether the sensitivity of the radiographer-performed double contrast barium enema (DCBE) differed from that of the radiologist-performed study. MATERIALS AND METHODS: Histologically proven cases of CRC were reviewed over a 3-year period to ascertain whether: the diagnosis had been made by DCBE in the 3 years before histological diagnosis; the lesion had been correctly diagnosed; the examination had been performed by a radiologist or radiographer. RESULTS: In the 3-year period there were 478 cases with histologically proven CRC. Of these, 239 (50%) had undergone DCBE as the initial radiological investigation of the colon. Sixty-four examinations had been performed by radiographers. A correct diagnosis was made in 58 cases (90.6%), the report was equivocal in one case (1.6%), there were four false-negatives (6.25%), and one case was abandoned (1.6%). One hundred and seventy-five examinations were performed by radiologists. A correct diagnosis was made in 157 cases (89.7%), the report was equivocal in one case (0.6%), there were 16 false-negatives (9.1%), and one case was abandoned (0.6%). CONCLUSION: A sensitivity of 90.6% for radiographer-performed studies compared favourably with 89.7% for radiologist-performed studies and supports the practice of radiographers undertaking barium enemas.

Requirement for DARPP-32 in progesterone-facilitated sexual receptivity in female rats and mice.

DARPP-32, a dopamine- and adenosine 3',5'-monophosphate (cAMP)-regulated phosphoprotein (32 kilodaltons in size), is an obligate intermediate in progesterone (P)-facilitated sexual receptivity in female rats and mice. The facilitative effect of P on sexual receptivity in female rats was blocked by antisense oligonucleotides to DARPP-32. Homozygous mice carrying a null mutation for the DARPP-32 gene exhibited minimal levels of P-facilitated sexual receptivity when compared to their wild-type littermates. P significantly increased hypothalamic cAMP levels and cAMP-dependent protein kinase activity. These increases were not inhibited by a D1 subclass dopamine receptor antagonist. P also enhanced phosphorylation of DARPP-32 on threonine 34 in the hypothalamus of mice. DARPP-32 activation is thus an obligatory step in progestin receptor regulation of sexual receptivity in rats and mice.

Confluent and reticulated papillomatosis responsive to selenium sulfide.

Confluent and reticulated papillomatosis of Gougerot and Carteaud (CRP) is a distinctive clinicopathologic entity, of unknown etiology, which shows some resemblance to pityriasis versicolor. A case of CRP that showed a significant therapeutic response to topical selenium sulfide is reported. In previously described cases, response to this agent and to other medications, both antifungal and keratolytic, has been variable. A review of these cases reveals conflicting evidence regarding the questionable role of Malassezia furfur in CRP.

Topical photochemotherapy for alopecia areata.

Twenty-two patients with alopecia areata were treated with a combination of topical 0.1% 8-methoxypsoralen and UVA (PUVA). Eight of the twenty-two patients (36.3%) responded with excellent regrowth (terminal hair in at least 75% of the treated scalp), and two patients (9.1%) showed good regrowth (terminal hair in 50% to 75% of the treated scalp). The mean total UVA exposure and the mean total number of treatments for the entire treatment course for these responders was 171.7 joules/cm2 and 47.4 treatments, respectively. Eight of the nine responders available for follow-up experienced some degree of relapse when PUVA treatments were tapered or during a follow-up period (mean, 8.3 months) after treatment was discontinued. Despite the failure of topical PUVA to change the long-term course of alopecia, the combination of PUVA with other therapeutic modalities may result in the prolongation of the beneficial effect in selected patients. The mechanism of action of PUVA in alopecia areata might involve an immunomodulatory effect.

Alopecia areata: pathogenesis and treatment.

Although its etiology remains unknown, evidence has accumulated to support an autoimmune pathogenesis for alopecia areata. Our review summarizes the immunologic data and also examines the role of genetics, atopy, and psychologic stress in this disorder. Until etiology is better understood, treatments for alopecia areata are likely to remain palliative. Nevertheless, newer therapies such as photochemotherapy, topical immunotherapy, and perhaps systemic immunotherapy (e.g., inosiplex) offer new hope for patients with extensive disease.

Topical treatment of alopecia areata.

It has been shown previously that alopecia areata can be treated with dinitrochlorobenzene (DNCB) and other contact allergens. Whether these agents work by inducing immunologic stimulation or simply a nonspecific inflammatory reaction has not been definitively demonstrated. To test the relative importance of these two mechanisms, we have randomly studied 22 patients with alopecia areata to whom either DNCB or croton oil was applied topically. Sixty-three percent of patients without spontaneous regrowth of hair regrew hair after DNCB application. None of those treated with croton oil regrew hair when treated later with DNCB. Therefore, a proved contact allergen was shown to be required for therapeutic success. Patient acceptance of the induced contact dermatitis was excellent. In light of recent data on the mutagenicity of DNCB to bacteria, other contact allergens for topical immunotherapy are being sought.