Association of Circulating Caprylic Acid with Risk of Mild Cognitive Impairment and Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative (ADNI) Cohort.

OBJECTIVE: Medium-chain fatty acids (MCFAs) can rapidly cross the blood-brain barrier and provide an alternative energy source for the brain. This study aims to determine 1) whether plasma caprylic acid (C8:0) is associated with risk of incident mild cognitive impairment (MCI) among baseline cognitively normal (CN) participants, and incident Alzheimer's Disease (AD) among baseline MCI participants; and 2) whether these associations differ by sex, comorbidity of cardiometabolic diseases, apolipoprotein E (APOE) ε4 alleles, and ADAS-Cog 13. METHODS: Within the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, plasma C8:0 was measured at baseline in 618 AD-free participants aged 55 to 91. Logistic regression models were used to estimate odds ratios (ORs) and 95% CIs with incident MCI and AD as dependent variables, separately. RESULTS: The inverse association between circulating C8:0 and risk of incident MCI was of borderline significance. The inverse association between circulating levels of C8:0 and risk of incident MCI was significant among CN participants with ≥1 cardiometabolic diseases [OR (95% CI): 0.75 (0.58-0.98) (P=0.03)], those with one copy of APOE ε4 alleles [OR (95% CI): 0.43 (0.21-0.89) (P=0.02)], female [OR (95% CI): 0.60 (0.38-0.94) (P=0.02)], and ADAS-Cog 13 above the median [OR (95%CI): 0.69 (0.50-0.97)(P=0.03)] after adjusting for all covariates. CONCLUSION: The inverse associations were present only among subgroups of CN participants, including female individuals, those with one or more cardiometabolic diseases, or one APOE ε4 allele, or higher ADAS-Cog 13 scores. If confirmed, this finding will facilitate precision prevention of MCI, in turn, AD among CN older adults.

Determination of soil nitrate and water content using attenuated total reflectance spectroscopy.

Direct determination of nitrate and soil moisture can significantly improve N-application management and thus reduce N-derived environmental pollution related to agriculture. Several studies have shown that Fourier transform infrared attenuated total reflectance (FT-IR/ATR) spectroscopy could be used to estimate the nitrate content of standardized soil pastes. Paste standardization appeared to be the main obstacle to in situ application of this approach, and the present study shows how FT-IR/ATR can be used to estimate both water content and nitrate concentration of field soil samples. Water content and nitrate concentration are determined sequentially using two subsamples of the initial soil sample. An a priori determined amount of highly concentrated nitrate solution is added to the first subsample and the ATR spectrum of this paste is used to estimate the sample water content. It is then possible to calculate the amount of water that should be added to the second subsample so that the resulting paste is very close to the ideal standard paste. Nitrate concentration, mg [N]/kg [dry soil], is estimated using the FT-IR/ATR spectrum of this second paste. Results are presented for a laboratory experiment with four agricultural soils, as well as for a field trial with a calcareous soil. For water content, the determination errors range from 0.01 to 0.02 g [water]/g [dry soil]. For nitrate concentration, the errors for three of the soils range from 5.9 to 8.4 mg [N]/kg [dry soil], while for the fourth, calcareous clay soil, the determination error is 13.6 mg [N]/kg [dry soil]. The determination errors obtained for the field trial are similar to the ones obtained for a similar soil under laboratory conditions, which shows the potential usefulness of the approach for improving N-application management and reducing environmental pollution.

Distinct Oral Neutrophil Subsets Define Health and Periodontal Disease States.

Neutrophils exit the vasculature and swarm to sites of inflammation and infection. However, these cells are abundant in the healthy, inflammation-free human oral environment, suggesting a unique immune surveillance role within the periodontium. We hypothesize that neutrophils in the healthy oral cavity occur in an intermediary parainflammatory state that allows them to interact with and contain the oral microflora without eliciting a marked inflammatory response. Based on a high-throughput screen of neutrophil CD (cluster of differentiation) marker expression and a thorough literature review, we developed multicolor flow cytometry panels to determine the surface marker signatures of oral neutrophil subsets in periodontal health and disease. We define here 3 distinct neutrophil subsets: resting/naive circulatory neutrophils, parainflammatory neutrophils found in the healthy oral cavity, and proinflammatory neutrophils found in the oral cavity during chronic periodontal disease. Furthermore, parainflammatory neutrophils manifest as 2 distinct subpopulations-based on size, granularity, and expression of specific CD markers-and exhibit intermediate levels of activation as compared with the proinflammatory oral neutrophils. These intermediately activated parainflammatory populations occur in equal proportions in the healthy oral cavity, with a shift to one highly activated proinflammatory neutrophil population in chronic periodontal disease. This work is the first to identify and characterize oral parainflammatory neutrophils that interact with commensal biofilms without inducing an inflammatory response, thereby demonstrating that not all neutrophils trafficking through periodontal tissues are fully activated. In addition to establishing possible diagnostic and treatment monitoring biomarkers, this oral neutrophil phenotype model builds on existing literature suggesting that the healthy periodontium may be in a parainflammatory state.

Effects of chemotherapy on bone marrow stroma in mice with acute myelogenous leukemia. Correlation with CFU-C and CFU-D.

This study describes changes in bone marrow stroma in murine acute myelogenous leukemia (AML). The AML was induced in C57B1 mice by intravenous (i.v.) transfusion of C4198 myelogenous leukemic cells. In untreated leukemic mice, the colony-forming unit fibroblasts (CFU-F) were severely inhibited. In leukemic mice treated by three chemotherapy protocols of cytosine-arabinoside (Ara-C) and adriamycin there was a 200% increase in the life span as compared to untreated leukemic animals and marked reduction of marrow leukemic load. In these mice the stromal inhibition was temporarily relieved, expressed by peaks of CFU-F2-3 days following each protocol. In between the peaks, CFU-F decreased to subnormal levels, remaining low to the end of the disease. In normal mice administered a similar chemotherapy regimen, there were peaks of CFU-F activation after each protocol and normal levels in between the peaks. Granulocyte/macrophage progenitors (CFU-C) of leukemic-treated and normal-treated mice showed increased levels following each chemotherapy protocol. Whereas CFU-C decreased below normal levels in leukemic mice towards the end of the disease, the level of these progenitors remained high in normal mice receiving Ara-C and adriamycin. Colony-forming units in diffusion chamber (CFU-D) showed mild fluctuations in both leukemic and normal mice receiving three protocols of Ara-C and adriamycin. It is possible that despite treatment, the bone marrow stroma in leukemia becomes irreversibly deficient towards the end of the disease and cannot support the residual normal hematopoiesis.

Bone marrow stromal deficiency in acute myeloid leukemia in mice.

A study of bone marrow stroma in acute myeloid leukemia (AML) in mice was carried out. AML was induced in C57B1 mice by i.v. inoculation of the C1498 cell line. There was a direct correlation between the marrow leukemic load and the degree of marrow stromal deficiency. This was expressed by reduced in vitro fibroblastoid colony formation. In co-cultures of normal mouse bone marrow and leukemic cells, and also in cultures of normal marrow with added conditioned medium (CM) of leukemic cells, marked inhibition of fibroblast-colony-forming units (CFU-F) from normal marrow was observed. In additional experiments, leukemic mice were treated with two consecutive injections of cytosine arabinoside (Ara-C) (2 X 200mg/kg) and sacrificed 48 h later. Bone marrow samples of treated animals formed in vitro an increased number of fibroblastoid colonies despite relatively high levels of marrow leukemia. It is concluded that: (a) there is a direct correlation between the incidence of marrow leukemic cells and the degree of stromal deficiency; (b) leukemic cells produce in vitro--and probably in vivo CFU-F inhibitory factors and (c) administration of restricted doses of cytosine arabinoside to leukemic mice reduces the marrow leukemic cell content to some extent and increases the capacity of CFU-F to form fibroblastoid colonies in vitro.

Heart failure in Parkinson's disease: analysis of the United States medicare current beneficiary survey.

OBJECTIVE: We sought to examine the prevalence of heart failure in elderly PD versus non-PD patients using a national sample of Medicare beneficiaries in the United States. SCOPE: The prevalence of heart failure in elderly PD patients was 2.27 times that of non-PD patients (19.4% versus 8.7%, 95% CI = 1.43-3.60, p 0.0005), and remained twice as high after excluding patients with stroke and possible vascular parkinsonism. CONCLUSIONS: In this cross-sectional study of a national Medicare database, heart failure occurred twice as frequently in elderly PD patients as in non-PD patients. Prospective studies are warranted to verify these findings.

Severe migraine associated with coarctation of aorta: complete recovery following balloon dilation.

We report on a rare association of severe migraine headaches associated with coarctation of aorta that completely resolved following dilation of the constricted aorta. A 6-year-old girl presented with severe pounding headaches accompanied with recurrent vomiting, associated with photophobia and phonophobia. She experienced frequent awakenings with severe headaches and vomiting. The described excruciating, prolonged, and practically persistent headaches were not relieved by analgesics and ergotamines. Neurologic assessment and brain computed tomography were both normal. A systolic murmur at the third right intercostal space prompted a cardiac echocardiogram, which demonstrated coarctation of the ascending aorta beyond the orifice of the left common carotid artery. Catheterization revealed a systolic gradient of 54 mm Hg, and the constricted lumen of the aorta was then dilated by a balloon. The excruciating vascular headaches and associated symptoms had abated instantaneously following this procedure. To the best of our knowledge, this is the first report associating severe migraine headaches in a child with coarctation of the aorta. Given complete recovery following balloon dilation of the aorta, cardiac echocardiogram should be added to the diagnostic battery of children with severe unresponsive migraine.

Microcystic adnexal carcinoma following radiotherapy in childhood.

A 36-year-old man was treated by radiotherapy for tinea capitis many years before discovery of microcystic adnexal carcinoma (MAC). Because of patient's refusal of any surgical intervention, we were able to follow the natural course of this tumor for 13 years. This case emphasizes the typical slow development of (MAC). The implication of the association of MAC and radiotherapy are discussed.

Raynaud's phenomenon as a presenting sign of metastatic melanoma.

The authors report a case of metastatic melanoma in a 22-year-old woman who initially presented with episodic attacks of digital ischemia. Review of the literature amassed another 22 cases of digital ischemia as an early or presenting feature of malignant disease. This is, however, the first description of Raynaud's phenomenon preceding by months the detection of a malignant melanoma. The possibility of occult malignant disease should be considered in evaluation of patients who present with digital ischemic changes without known predisposing conditions.

Burn patients' use of autohypnosis: making a painful experience bearable.

Autohypnosis (that is performing hypnosis in the absence of the therapist) was used for adjuvant analgesic and anxiolytic therapy in 18 burn patients. It combines the advantages of hypnosis without being limited by the availability of the hypnotic therapist immediately prior to painful activities. Autohypnosis is less time and labour consuming, and therefore less expensive. Out of 180 patients treated with autogenic relaxation techniques only 48 (27 per cent) entered a state of hypnosis that enabled them to cope with their pain, and 18 (10 per cent) achieved autohypnosis. Most of these patients needed some auxiliary devices such as recorded instructions or telephone calls.

[Sex reassignment surgery in a trans-sexual].

Trans-sexualism is a psychiatric disorder characterized by the conviction that one's gender identity does not conform to one's biological sex. The current Diagnostic and Statistical Manual of Mental Disorders gives 5 diagnostic criteria for trans-sexualism which most health care professionals accept. Although many trans-sexuals derive some gratification from assuming roles appropriate to their desired gender, a substantial number are convinced that only sexual transformation can bring meaningful relief of their feelings of despair. Approximately 2/3 of trans-sexuals who undergo sex reassignment procedures are improved at follow-up. A relatively advanced age and secondary trans-sexualism (transvestites and effeminate homosexuals) are risk factors for poor prognosis in those requesting sex reassignment. In recent decades the demand for sex reassignment has increased, as have the number and variety of psychological, hormonal and surgical treatments proposed. The operative procedures currently employed for sex reassignment give reasonably good esthetic and functional results, and in 1986 the Israel Ministry of Health permitted its government hospitals to perform them. A 23-year-old male trans-sexual is reported who underwent successful surgery for sex change and now, 1 year later, is satisfied with the result.

[Moh's micrographic surgery: first experience in Israel].

Moh's micrographic surgery is a method by which cancer of the skin may be excised under complete microscopic control. It consistently offers the highest cure rate in the treatment of malignancy of the skin, while the least amount of uninvolved tissue is sacrificed. This, the first center for Moh's micrographic surgery in Israel, started functioning in 1989. The first 50 patients included 33 women (average age 50.7 years) and 17 men (average age 60.6 years) suffering from basal cell carcinoma of the face. 56% of the patients were referred for Moh's surgery after failure of other primary treatments, and the rest were referred due to the problematic location of the lesion or its size. 13 patients (28%) were referred after previous treatment with solcoderm (Mardi's method). In these patients the lesions were especially deep and aggressive.

[Resection of invasive orbital tumors and reconstruction with temporalis muscle flap].

3 patients with invasive basal cell carcinoma of the skin which necessitated orbital exenteration are reported. In all 3 treatment was delayed, primary therapy was inadequate and the tumor had reached massive size. Excision of the orbital contents is a radical, mutilating procedure, but in advanced cases of malignant orbital tumors it offers the only chance for survival. The temporalis muscle flap is adaptable, well supplied with blood, and contains a large mass of tissue. Its utilization provides a simple, uncomplicated and effective technique for orbital reconstruction following massive resection. It gives a relatively effective result which is usually acceptable to the patient.

[Lateral arm free flap transfer to cover traumatic hand injuries].

The advantages of free flaps over distant pedicled flaps in hand reconstruction are well documented. They often require only a single operation, do not depend on local conditions of the wound and permit early physiotherapy. The lateral arm free flap is essentially suitable for reconstruction of the hand. It is thin, potentially sensate, and gives nearly perfect skin color and texture match. An additional technical advantage is the possibility of elevating the lateral arm free flap with tourniquet control at the same surgical field as the recipient site. We describe 3 cases of traumatic damage to skin and soft tissue of the hand, in which reconstruction was by both elective and emergency lateral arm, free flap transfer. They demonstrate the merits of this method of reconstruction.

The practice of neurology, 2000-2010: report of the AAN Member Research Subcommittee.

OBJECTIVE: To present an analysis of American Academy of Neurology (AAN) membership demographics and practice trends over the past decade. METHODS: Data from the 2009 AAN Census and 2010 Practice Profile Form (PPF) surveys were compared to results from 2004 and 2000 surveys. The Census was sent to all AAN members, and the PPF was sent to a random sample of US practicing neurologists. RESULTS: Since 2000, AAN membership increased by 31%, and the number of US neurologist-members increased by 14%. Mean age of US neurologists increased from 48.6 to 53.3 years, and 23.9% of neurologists are women. There was a 15% increase in the proportion of neurologists relative to the US population, from 3.41 neurologists per 100,000 population in 2000 to 3.92 neurologists in 2009. In 2009, 24.1% of US neurologists were in solo practice, 27.8% were in a neurology group, and 35.6% were in multispecialty/university settings, with little change in practice arrangements over time. The top 5 practice interest areas were unchanged since 2004 as were the number of hours devoted to patient care (42.3) or total work hours per week (57.1). Little change was observed in performed procedures, except increased use of botulinum toxin and nerve blocks and a decline in lumbar punctures. Neurologists rely more on physician assistants to see follow-up and new patients independently (p < 0.001). CONCLUSION: Despite advances in neurologic diagnosis and therapy, there has been little change in practice characteristics of US neurologists.

Association between late-life body mass index and dementia: The Kame Project.

OBJECTIVE: To examine the association between body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) and risk of dementia and its subtypes in late life. METHODS: Participants were members of the Kame Project, a population-based prospective cohort study of 1,836 Japanese Americans living in King County, WA, who had a mean age of 71.8 years and were dementia-free at baseline (1992-1994), and were followed for incident dementia through 2001. Cox proportional hazards models were used to estimate the risk of dementia, Alzheimer disease (AD), and vascular dementia (VaD) controlling for demographic and lifestyle characteristics and vascular comorbidities as a function of baseline BMI, WC, and WHR and change in BMI over time. RESULTS: Higher baseline BMI was significantly associated with a reduced risk of AD (hazard ratio [HR] = 0.56, 95% confidence interval [CI] = 0.33-0.97) in the fully adjusted model. Slower rate of decline in BMI was associated with a reduced risk of dementia (HR = 0.37, 95% CI = 0.14-0.98), with the association stronger for those who were overweight or obese (HR = 0.18, 95% CI = 0.05-0.58) compared to normal or underweight (HR = 1.00, 95% CI = 0.18-5.66) at baseline. CONCLUSION: Higher baseline body mass index (BMI) and slower declining BMI in late life are associated with a reduced risk of dementia, suggesting that low BMI or a faster decline in BMI in late life may be preclinical indicators of an underlying dementing illness, especially for those who were initially overweight or obese.

Prevalence of dementia in Chamorros on Guam: relationship to age, gender, education, and APOE.

OBJECTIVES: To estimate the prevalence of dementia and its clinical subtypes among Chamorros on Guam aged 65 years or older and to examine associations with age, gender, education, and APOE genotype. BACKGROUND: Chamorros, the indigenous people of Guam, had a high incidence of ALS and parkinsonism-dementia complex (PDC), in the 1950s. Over the next 50 years, ALS incidence declined markedly, but PDC only slightly. The prevalence of late life dementia in Chamorros and its relationship to ALS/PDC are unknown. METHODS: Island-wide population-based survey of Chamorros aged 65 years or older as of January 1, 2003. Two-stage assessment: cognitive and motor screening, followed by neurologic and psychometric evaluation. Data were reviewed at consensus conference to make clinical diagnoses. RESULTS: Of 2,789 Chamorros aged 65 years or older, 73% were enrolled; 27% declined participation, died before contact or screening, or moved off Guam. The point prevalence of all-cause dementia on February 1, 2004, was 12.2%. Prevalence data for subtypes were as follows: Guam dementia (clinically equivalent to AD), 8.8%; PDC, 1.5%; pure vascular dementia, 1.3%; other, 0.6%. The prevalence of dementia rose exponentially with age. Low education was significantly associated with dementia, but gender was not. There was a trend toward higher PDC prevalence among men. The APOE epsilon4 allele was not associated with dementia. CONCLUSIONS: The prevalence of dementia among elderly Chamorros is relatively high. Guam dementia is the most common diagnosis and exceeds parkinsonism-dementia complex. Age and low education are strongly associated with dementia, but gender and APOE epsilon4 are not. Incidence studies will allow risk factors for dementia to be clarified.