Were climatic forcings the main driver for mid-holocene changes in settlement dynamics on the Varamin Plain (Central Iranian Plateau)?

Settlement crises in ancient cultures of Western Asia are commonly thought to be caused by climatic events such as severe droughts. However, the insufficient climate proxy situation in this region challenges the inference of clear relationships between climate and settlement dynamics. We investigate the Holocene climatic changes on the Varamin Plain in the context of the climatic history of Western Central Asia by using a transient comprehensive Earth System Model simulation (8 ka BP to pre-industrial), a high-resolution regional snapshot simulation and a synthesis of pollen-based climate reconstructions. In line with the reconstructions, the models reveal only slightly varying mean climatic conditions on the Varamin Plain but indicate substantial changes in seasonality during the Holocene. Increased precipitation during spring, combined with lower temperature and potentially stronger snow accumulation on the upstream Alborz mountains may have led to an increased water supply on the alluvial fan during the vegetation period and thus to more favourable conditions for agricultural production during the Mid-Holocene compared to modern times. According to the model, dry periods on the Central Iranian Plateau are related to particularly weak Westerly winds, fostering the subsidence in the mid-troposphere and hampering precipitation over the region. The model reveals that dry periods have spatially heterogenous manifestations, thus explaining why they do not appear in all proxy records in the wider study region. In fact, the climatic signal may depend on local environmental conditions. The interaction of the topography with the atmospheric circulation leads to additional spatial heterogeneity. Although our results provide several indications for a connection between climate and settlement dynamics, the small overall changes in moisture call into question whether climate is the main driver for settlement discontinuities on the Central Iranian Plateau. To shed further light on this issue, more high-resolution long-term proxy records are needed.

Auto regulatory capacity of the thyroid gland after numerous iodinated contrast media investigations.

Excess of iodine may interfere with thyroid function. It is unclear to what extent the thyroid function is disturbed by repeated infusion of iodide contrast agent (IC) used during X-ray examinations. Thyroid function tests free T4 (FT4), free FT3 (FT3), thyroid-stimulating hormone (TSH), TSH receptor antibodies (TRAb) and thyroid peroxidase antibodies (TPO-Ab) were measured in a group of Norwegian patients with an assumed normal iodine balance before, 1 and 6 weeks after IC infusion. Forty patients (19 females and 21 men) referred for routine CT were included. Thirty two out of 40 patients had previously undertaken IC investigations. The mean TSH concentration was 2.1 mIU/l ± 1.7 at the baseline, increased to 2.9 ± 2.5 after 1 week (p < .001), and reverted to nearly initial values 1.4 ± 0.8 after 6 weeks. Initially the mean FT4 was 14.1 pmol/l ± 1.9 FT4, reduced to 13.3 pmol/l ± 2.5 (p = .009) after 1 week, and returned to 14.0 pmol/l ± 2.5 after 6 weeks, comparable to the initial values (p > .05). FT3 levels did not change during the period. There was no relationship between FT4, or TSH and age, gender, cancer/not cancer, number or frequency of earlier IC investigations. In conclusion, IC induces changes in thyroid function tests, however, they return to normal levels after 6 weeks. Our results suggest adequate auto regulatory capacity of the thyroid gland even in those with repeated contrast investigations (up to 40). Routine testing of thyroid function should therefore not be undertaken in this patient group.

The Incidence of Diagnosis of Munchausen Syndrome, Other Factitious Disorders, and Malingering.

BACKGROUND: Systematic studies on factitious disorders and malingering in large populations are rare. To address this issue, we performed a nationwide epidemiological study in Norway on the incidence of these diagnoses in an unselected patient population. In particular, we tried to confirm the diagnoses and to estimate the contribution of Munchausen syndrome to the spectrum of factitious disorders. METHODS: We analyzed data obtained from the Norwegian Patient Registry (NPR), which provided a deidentified list of all patients from 2008 to 2016 who had received the ICD-10 diagnosis of F68.1 or the diagnosis code Z76.5. RESULTS: Altogether, 237 patients (99 females; 138 males) received a diagnosis of F68.1. Code Z76.5 was applied to 52 patients (12 females; 40 males), all diagnosed within health institutions. Three of 1700 specialists (somatic specialist, psychologist, or psychiatrist) in private practice had diagnosed a factitious disorder in altogether 87 patients. After contacting these specialists, we could identify no true case of F68.1. For 24 of 146 patients who were equally distributed by gender within health institutions, we managed to identify the diagnosing healthcare providers. Of these 24 patients, only 11 correctly qualified for code F68.1. Only two female patients qualified for a Munchausen syndrome diagnosis. CONCLUSIONS: There is a male predominance for the diagnosis of malingering. An earlier suspicion of a female predominance for Munchausen syndrome is upheld. There is significant underdiagnosing and misdiagnosing for both conditions and for factitious disorders in general. To separate the most serious form of factitious disorders from milder forms and to facilitate more systematic research, we recommend a specific ICD diagnosis for Munchausen syndrome.

Expression of nucleotide excision repair in Alzheimer's disease is higher in brain tissue than in blood.

Age-related changes are increased in patients with Alzheimer's disease (AD), including oxidative stress and DNA damage. We propose that genotoxic stress and DNA repair responses influence neurodegeneration in the pathogenesis of AD. Here, we focus on nucleotide excision repair (NER). Real-time qPCR and mass spectrometry were employed to determine the expression levels of selected NER components. The mRNA levels of the genes encoding the NER proteins RAD23B, RPA1, ERCC1, PCNA and LIG3 as well as the NER-interacting base excision repair protein MPG in blood and brain tissue from four brain regions in patients with AD or mild cognitive impairment and healthy controls (HC), were assessed. NER mRNA levels were significantly higher in brain tissue than in blood. Further, LIG3 mRNA levels in the frontal cortex was higher in AD versus HC, while mRNA levels of MPG and LIG3 in entorhinal cortex and RPA1 in the cerebellum were lower in AD versus HC. In blood, RPA1 and ERCC1 mRNA levels were lower in AD patients than in HC. Alterations in gene expression of NER components between brain regions were associated with AD, connecting DNA repair to AD pathogenesis and suggesting a distinct role for NER in the brain.

Bioaccumulation and trophic transfer of cyclic volatile methylsiloxanes (cVMS) in the aquatic marine food webs of the Oslofjord, Norway.

The trophic transfer of cyclic methylsiloxanes (cVMS) in aquatic ecosystems is an important criterion for assessing bioaccumulation and ecological risk. Bioaccumulation and trophic transfer of cVMS, specifically octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), and dodecamethylcyclohexasiloxane (D6), were evaluated for the marine food webs of the Inner and Outer Oslofjord, Norway. The sampled food webs included zooplankton, benthic macroinvertebrates, shellfish, and finfish species. Zooplankton, benthic macroinvertebrates, and shellfish occupied the lowest trophic levels (TL ≈2 to 3); northern shrimp (Pandalus borealis) and Atlantic herring (Clupea harengus) occupied the middle trophic levels (TL ≈3 to 4), and Atlantic cod (Gadus morhua) occupied the highest tropic level (TL>4.0). Trophic dynamics in the Oslofjord were best described as a compressed food web defined by demersal and pelagic components that were confounded by a diversity in prey organisms and feeding relationships. Lipid-normalized concentrations of D4, D5, and D6 were greatest in the lowest trophic levels and significantly decreased up the food web, with the lowest concentrations being observed in the highest trophic level species. Trophic magnification factors (TMF) for D4, D5, and D6 were <1.0 (range 0.3 to 0.9) and were consistent between the Inner and Outer Oslofjord, indicating that exposure did not impact TMF across the marine food web. There was no evidence to suggest biomagnification of cVMS in the Oslofjord. Rather, results indicated that trophic dilution of cVMS, not trophic magnification, occurred across the sampled food webs.

Micronutrients and the risk of hip fracture: Case-control study.

BACKGROUND: Vitamin D, and possibly vitamin K, has an established association to fracture risk. Other vitamins are, however, less studied. AIM: To determine whether specific micronutrients other than 25(OH)D and vitamin K play a role in risk of hip fracture and bone turnover. METHODS: In this case-control study, blood was drawn for measurements of vitamins A, B6, B12, C, E, and folic acid as well as the bone turnover markers osteocalcin and bone-specific alkaline phosphatase upon admission for hip fracture in 116 patients and in 73 home-dwelling non fractured controls. Results for vitamin K1 and 25(OH)D from the same populations have been reported previously. RESULTS: Low vitamin A, C, and E concentrations were independently associated with a risk of hip fracture. The adjusted odds ratio (95% confidence interval) per 10 µmol/L increase in vitamin A concentration was 0.74 (0.65-0.84); for 1 µmol/L vitamin C and E: 0.94 (0.92-0.97) and 0.81 (0.74-0.89) respectively. The results were principally unchanged when 25(OH)D, vitamin K1, Body Mass Index, and other potential confounders were adjusted for. All vitamins except B12 and folic acid correlated positively with total osteocalcin and negatively with bone-specific alkaline phosphatase. CONCLUSIONS: Low vitamin A, C, and E concentrations are associated with an increased risk of hip fracture, possibly mediated through bone turnover mechanisms. This case-control study is registered at: ClinicalTrials.gov. NCT01738776. The patient related outcome is also registered at: ClinicalTrials.gov. NCT01009268.

Normal Vitamin Levels and Nutritional Indices in Alzheimer's Disease Patients with Mild Cognitive Impairment or Dementia with Normal Body Mass Indexes.

Evidence supports an association between vitamin deficiencies and cognitive decline in Alzheimer's disease (AD). If vitamin deficiencies are causative for AD development, they should be detectable during very early stages of AD. Here we investigated nutritional factors among home-living patients diagnosed with mild cognitive impairment (MCI) or mild dementia due to AD, compared to healthy controls. Our study included 73 patients with AD (25 with MCI, 48 with dementia) and 63 cognitively intact age-matched controls. All participants underwent cognitive testing, somatic examination, and measurements of vitamins A, B1, B6, folate, B12, C, D, and E, and F2-α-isoprostane. Results are given as mean (SD). MMSE scores were 29.1 (1.0) for healthy controls, 27.4 (1.8) for patients with MCI, and 24.3 (3.2) for patients with dementia. Vitamin concentrations for the these groups, respectively, were as follows: B1 (nmol/l), 157 (29), 161 (35), and 161 (32); B6 (nmol/l), 57 (63), 71 (104), and 58 (44); folate (mmol/l), 23 (9), 26 (10), and 23 (11); B12 (pmol/l), 407 (159), 427 (116), and 397 (204); C (µmol/l), 63 (18), 61 (16), and 63 (29); A (µmol/l), 2.3 (0.6), 2.2 (0.5), and 2.3 (0.5); E (µmol/l), 36 (6.3), 36 (6.9), and 36 (8.2); 25-OH vitamin D (nmol/l), 65 (18), 61 (19), and 65 (20); and 8-iso-PGFα (pg/ml), 64 (27); 60 (19), and 66 (51). These concentrations did not significantly differ (p≤0.05) between the three groups. Our results do not support the hypothesis that vitamin deficiencies play a causative role in the development of early cognitive impairment.

Five-year outcomes after laparoscopic gastric bypass and laparoscopic duodenal switch in patients with body mass index of 50 to 60: a randomized clinical trial.

IMPORTANCE: There is no consensus as to which bariatric procedure is preferred to reduce weight and improve health in patients with a body mass index higher than 50. OBJECTIVE: To compare 5-year outcomes after Roux-en-Y gastric bypass (gastric bypass) and biliopancreatic diversion with duodenal switch (duodenal switch). DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical open-label trial at Oslo University Hospital, Oslo, Norway, and Sahlgrenska University Hospital, Gothenburg, Sweden. Participants were recruited between March 17, 2006, and August 20, 2007, and included 60 patients aged 20 to 50 years with a body mass index of 50 to 60. The current study provides the 5-year follow-up analyses by intent to treat, excluding one participant accepted for inclusion who declined being operated on prior to knowing to what group he was randomized. INTERVENTIONS: Laparoscopic gastric bypass and laparoscopic duodenal switch. MAIN OUTCOMES AND MEASURES: Body mass index and secondary outcomes including anthropometric measures, cardiometabolic risk factors, pulmonary function, vitamin status, gastrointestinal symptoms, health-related quality of life, and adverse events. RESULTS: Sixty patients were randomly assigned and operated on with gastric bypass (n = 31) and duodenal switch (n = 29). Fifty-five patients (92%) completed the study. Five years after surgery, the mean reductions in body mass index were 13.6 (95% CI, 11.0-16.1) and 22.1 (95% CI, 19.5-24.7) after gastric bypass and duodenal switch, respectively. The mean between-group difference was 8.5 (95% CI, 4.9-12.2; P < .001). Remission rates of type 2 diabetes mellitus and metabolic syndrome and changes in blood pressure and lung function were similar between groups. Reductions in total cholesterol, low-density lipoprotein cholesterol, triglycerides, and fasting glucose were significantly greater after duodenal switch compared with gastric bypass. Serum concentrations of vitamin A and 25-hydroxyvitamin D were significantly reduced after duodenal switch compared with gastric bypass. Duodenal switch was associated with more gastrointestinal adverse effects. Health-related quality of life was similar between groups. Patients with duodenal switch underwent more surgical procedures related to the initial procedure (13 [44.8%] vs 3 [9.7%] patients; P = .002) and had significantly more hospital admissions compared with patients with gastric bypass. CONCLUSIONS AND RELEVANCE: In patients with a body mass index of 50 to 60, duodenal switch resulted in greater weight loss and greater improvements in low-density lipoprotein cholesterol, triglyceride, and glucose levels 5 years after surgery compared with gastric bypass while improvements in health-related quality of life were similar. However, duodenal switch was associated with more surgical, nutritional, and gastrointestinal adverse effects. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00327912.

Vitamin K1 and 25(OH)D are independently and synergistically associated with a risk for hip fracture in an elderly population: a case control study.

BACKGROUND & AIMS: The incidence of hip fractures in Oslo is among the highest in the world. Vitamin D, as well as vitamin K, may play an important role in bone metabolism. We examined if vitamin K1 and 25(OH)D were associated with an increased risk of hip fracture, and whether the possible synergistic effect of these two micronutrients is mediated through bone turnover markers. METHODS: Blood was drawn for vitamin K1, 25(OH)D, and the bone turnover marker osteocalcin upon admission for hip fracture and in healthy controls. RESULTS: Vitamin K1 and 25(OH)D were independently associated with a risk of hip fracture. The adjusted odds ratio (95% CI) per ng/ml increase in vitamin K1 was 0.07 (0.02-0.32), and that per nmol/L increase in 25(OH)D was 0.96 (0.95-0.98). There was a significant interaction between 25(OH)D and vitamin K1 (p < 0.001), and a significant correlation between total osteocalcin and vitamin K1 and 25(OH)D (rho = 0.18, p = 0.01; rho = 0.20, p = 0.01, respectively). CONCLUSIONS: Vitamin K1 and 25(OH)D are lower in hip fracture patients compared with controls. Vitamin K1 and 25(OH)D are independently and synergistically associated with the risk of hip fracture when adjusting for confounders. Intervention studies should include both vitamins.

Abscess infections and malnutrition--a cross-sectional study of polydrug addicts in Oslo, Norway.

BACKGROUND: Injection drug use and malnutrition are widespread among polydrug addicts in Oslo, Norway, but little is known about the frequency of abscess infections and possible relations to malnutrition. OBJECTIVES: To assess the prevalence of abscess infections, and differences in nutritional status between drug addicts with or without abscess infections. DESIGN: A cross-sectional study of 195 polydrug addicts encompassing interview of demographics, dietary recall, anthropometric measurements and biochemical analyses. All respondents were under the influence of illicit drugs and were not participating in any drug treatment or rehabilitation program at the time of investigation. RESULTS: Abscess infections were reported by 25% of the respondents, 19% of the men and 33% of the women (p = 0.025). Underweight (BMI < 18.5 kg/m(2)) was significantly more prevalent in the abscess infected than in the non-abscess-infected group (p = 0.001). The abscess-infected addicts reported fewer meals, lower intakes of fruits and vegetables, lower energy percentage (E%) from protein and higher E% from sugar. They also had lower total intakes of vitamins D, B1, B6, B12, folic acid and vitamin C than the non-abscess-infected group. The two groups differed significantly with respect to S-C-peptide (p = 0.042) and B-HbA1c (p = 0.012), and the prevalence of hyperhomocysteinemia (P-tHCY > 15 µmol/L) was 73% in the abscess-infected group and 41% in the non-abscess-infected group (p = 0.001). The concentrations of S-25-hydroxy-vitamin D3 was very low. CONCLUSION: The prevalence of abscess infections was 25% among the examined polydrug addicts. Dietary, anthropometric and biochemical assessment indicated a relation between abscess infections and malnutrition.

Siberian larch forests and the ion content of thaw lakes form a geochemically functional entity.

Siberian larch forests growing on shallow permafrost soils have not, until now, been considered to be controlling the abiotic and biotic characteristics of the vast number of thaw-lake ecosystems. Here we show, using four independent data sets (a modern data set from 201 lakes from the tundra to taiga, and three lake-core records), that lake-water geochemistry in Yakutia is highly correlated with vegetation. Alkalinity increases with catchment forest density. We postulate that in this arid area, higher evapotranspiration in larch forests compared with that in the tundra vegetation leads to local salt accumulation in soils. Solutes are transported to nearby thaw lakes during rain events and snow melt, but are not fully transported into rivers, because there is no continuous groundwater flow within permafrost soils. This implies that potentially large shifts in the chemical characteristics of aquatic ecosystems to known warming are absent because of the slow response of catchment forests to climate change.

Secondary hyperparathyroidism, vitamin D sufficiency, and serum calcium 5 years after gastric bypass and duodenal switch.

BACKGROUND: The prevalence of secondary hyperparathyroidism (SHPT) is high after bariatric surgery. Vitamin D is supplied to counteract SHPT and bone disease, and we studied vitamin D associations with SHPT. METHODS: We measured serum levels of 25-OH vitamin D and parathyroid hormone (PTH) 5 years after gastric bypass and duodenal switch. One hundred twenty-five patients were included, of whom 114 (91 %) had undergone gastric bypass and 11 (9 %) had undergone duodenal switch. SHPT was defined as PTH > 7.0 pmol/l in the absence of hypercalcemia. 25-OH vitamin D levels were divided into three categories: <50, 50-74, and ≥75 nmol/l. Serum ionized calcium, magnesium, phosphate, and creatinine were divided into tertiles. RESULTS: Mean age ± SD was 44 ± 9 years at 5 years follow-up. Ninety out of 125 (72 %) patients were women. SHPT was present in 45 out of 114 (40 %) gastric bypass patients and in 11 out of 11 (100 %) duodenal switch patients. The prevalence was high in all vitamin D categories studied. An inverse association between ionized calcium and PTH was found. For the gastric bypass patients, the odds ratio for SHPT in the upper two tertiles of ionized calcium was 0.35; 95 % CI, 0.15-0.79; p = 0.011, compared with the lowest tertile. Supplements of vitamin D and calcium were not associated with a lower prevalence of SHPT at 5 years follow-up. CONCLUSIONS: The prevalence of SHPT was high 5 years after gastric bypass and duodenal switch. SHPT was inversely associated with serum ionized calcium, but not with vitamin D. The supplementation used was insufficient to compensate for the impaired calcium absorption after surgery.

Vitamin status after gastric bypass and lifestyle intervention: a comparative prospective study.

BACKGROUND: Bariatric surgery can lead to vitamin deficiencies. We aimed to assess the changes in blood vitamin concentrations in patients who were taking predefined supplements after gastric bypass surgery. METHODS: A total of 29 patients underwent gastric bypass and 24 unmatched controls underwent lifestyle intervention in a prospective, nonrandomized trial. The patients in the surgical group received multivitamin, iron, calcium, vitamin D, and vitamin B(12) supplements. No supplements were prescribed to the lifestyle group. The median body mass index decreased from 46 to 32 kg/m(2) after surgery and from 40 to 39 kg/m(2) after lifestyle intervention. RESULTS: Of the 53 included patients, 50 completed the 1-year follow-up examination (94%). Compared with the lifestyle patients, the surgical patients had increased vitamin B(6), folic acid, vitamin B(12), and lipid-adjusted vitamin E (P <.02 for each) concentrations but decreased vitamin A concentrations (P <.01) during follow-up. No significant difference between the 2 groups was found for vitamin B(1), vitamin C, or 25-hydroxyvitamin D. Most surgical patients reported taking their supplements. CONCLUSION: Gastric bypass patients adhering to a set of dietary supplements had mostly stable or increased vitamin concentrations compared with both their baseline values and the changes in a nonsurgical control group.

Effect of bariatric surgery on sulphur amino acids and glutamate.

Plasma total cysteine (tCys) concentrations are associated with BMI. To study the relationship between tCys and BMI, we monitored the changes in serum concentrations of tCys and metabolically related compounds in sixty obese patients (BMI 50-60 kg/m(2)) from before to 1 year after either gastric bypass surgery (mean 30 % weight loss) or duodenal switch surgery (mean 41 % weight loss). A total of fifty-eight healthy persons (BMI 17-31 kg/m(2)) served as controls. Before surgery, obese patients had modestly (approximately 17 %) higher mean serum tCys, and markedly (>2-fold) higher glutamate concentrations, than controls (P ≤ 0·001 for both). Serial examinations after surgery revealed that gastric bypass patients had no change in tCys concentrations (P = 0·22), while duodenal switch patients showed a modest (approximately 12 %) but significant decrease in tCys (P < 0·001). Total homocysteine concentrations increased in duodenal switch patients but not in gastric bypass patients. Independent of surgery type, serum concentrations of methionine and cystathionine decreased (P < 0·05 for both), while serum glutathione and taurine remained stable. Glutamate concentrations declined, as did γ-glutamyltransferase activity (P < 0·001 for both). These results show that despite 30 % weight loss, and decreases in methionine, cystathionine and glutamate, there was no significant change in serum tCys in patients after gastric bypass surgery. The decrease in tCys in patients undergoing duodenal switch could be related to malabsorption. The present findings do not suggest that BMI is a causal determinant of plasma tCys.

Bimodal distribution of polyunsaturated fatty acids in schizophrenia suggests two endophenotypes of the disorder.

BACKGROUND: There is conflicting evidence of whether polyunsaturated fatty acids (PUFA) in red blood cells are bimodally distributed in schizophrenia. The purpose of this study was to examine the distribution of PUFA, as well as its links to plausible causal factors. METHODS: A 16-week cohort study and a case-control study as part of a randomized controlled trial. Ninety-nine patients with DSM-IV schizophrenia, schizoaffective disorder, or schizophreniform disorder, aged 18 to 39, were consecutively included at admission to psychiatric departments of nine Norwegian hospitals. Fatty acids were measured in 97 of these patients and in 20 healthy control subjects. The primary outcome measure was the bimodality test statistic T, assessed by a χ(2) test of the likelihood of one or two normal distributions of PUFA. RESULTS: At baseline, levels of polyunsaturated fatty acids were highly significantly bimodally distributed among patients. One third of patients constituted a group (low PUFA) who had PUFA levels at one fifth (p < .001) of those in high PUFA patients and healthy control subjects, which did not differ. Bimodality was mainly accounted for by docosahexaenoic acid and arachidonic acid. Bimodality was confirmed after 16 weeks. α-tocopherol was a robust predictor of PUFA at both occasions. Desaturase and elongase indexes differed between PUFA groups. Smoking, gender, antipsychotic medication, and dietary factors did not explain the bimodal distribution. CONCLUSIONS: Red blood cell PUFA were bimodally distributed among acutely ill patients with schizophrenia and schizoaffective disorder. Endogenous deficiencies of redox regulation or synthesis of long-chain PUFA in the low PUFA group may explain our findings.