Single-Fraction Gamma-Knife Radiosurgery with or without Previous Surgery for Cavernous Sinus Meningiomas: A Single-Center Experience and Systematic Literature Review.

Background: The most effective treatment method for meningiomas is surgical treatment. However, complete resection of cavernous sinus meningiomas is quite difficult. The biggest reasons for this are; narrow surgical corridor, the optic chiasm is the close relationship between the cranial nerves and anterior cerebral and internal carotid arteries. Gamma knife radiosurgery (GKRS) may be a good option in these lesions with high mortality and morbidity. Aim: This study aimed to evaluate and compare the early effects at a mean of 6 months and 3 years and outcomes between surgery followed by gamma knife radiosurgery (GKRS) and GKRS alone for cavernous sinus meningiomas. Methods: We included 20 patients with cavernous sinus meningioma treated via single fraction Leksell Gamma Knife Perfexion (Elekta Instruments; Stockholm, Sweden) between 2015 and 2018. The mean age of the patients was 54.95 (range: 32-77) years. Nine patients underwent primary surgery (for the resection of extracavernous components of the tumor) followed by GKRS (for the resection of intracavernous components of the tumor) (group A). Meanwhile, 11 patients were managed with GKRS alone (group B). The tumor volume ranged from 2.8 to 32.8 (mean: 14.76) cm3 and the isodose to the tumor margin from 10 to 13.5 (mean: 11.65) Gy. Results: In total, 20 patients were followed up at a mean time of 18.95 (range: 6-36) months. The mean Karnofsky Performance Score of the patients was 95.2%. The mean follow up times of groups A and B were 23.6 and 15 months, respectively. Meanwhile, only patients with a follow up time of at least 6 months were included in the study. The mean follow up time after GKRS in group A was 17.6 months. There was no change in the tumor volume in 15% of patients. In the remaining cases, the tumor volume decreased. The mean tumor regression rates were 82.2% in Group A and 17.7% in Group B. The tumor volume did not decrease in three patients (n = 1, group A and n = 2, group B). Cranial nerve deficits improved, worsened, and remained stable in 46.6%, 26.6%, and 26.6% of cases, respectively. The temporary morbidity rate was 10%. In group A, transient postoperative diabetes insipidus was observed in one patient and atelectasis in another. None of these complications affected the final status of patients. The mortality rate after treatment was 0%. Conclusion: Volume staged GKRS is safe and effective for cavernous sinus meningioma. GKRS is effective for long term tumor growth control and has a low complication rate. Hence, it is the preferred management strategy for tumors with a suitable volume (average tumor diameter: 3 cm or volume: 10 cm3 ). In tumors with a volume of more than 10 mL and/or without a 3 mm safety margin with the optical system, it is recommended to prepare for radiosurgery by cytoreducing the tumor volume surgically. Based on our opinion, the best results were obtained by GKRS to the intracavernous.

A Theoretical Investigation of Cu+ , Ni2+ and Co2+ -Exchanged Zeolites for Hydrogen Storage.

This study investigates the H2 adsorption on Cu+ , Ni2+ and Co2+ -exchanged SSZ-13 (CHA) and SSZ-39 (AEI) using periodic DFT computations. The most stable Cu+ position was found to be the 6-membered-ring window for both zeolites. Similarly, for the investigated Ni2+ and Co2+ loadings on 6-membered-ring windows, the third nearest neighbor Al positions, i. e., Al-O-Si-O-Si-O-Al coordination, was found to be the most stable position. H2 adsorption was investigated for all the Cu+ , Ni2+ and Co2+ centers. AEI and CHA resulted in similar H2 -Cu interactions for the Al and B substituted structures. H2 adsorption on Cu+ located in the 8-membered-ring gave the highest adsorption energy for both frameworks. Replacing Al with B in the framework increased the electron back donation from Cu+ (3d) orbitals to H2 antibonding orbital (σH2 * ). The H2 adsorption energies on the Ni2+ and Co2+ -exchanged zeolites were found to be between -15 and -44 kJ/mol. Higher energy values were observed on the AEI framework, especially when two Al atoms have the Al-O-Si-O-Al configuration. Lesser interaction of the d-orbitals in the case of the Co2+ and Ni2+ cations resulted in heat of H2 adsorption close to optimum values required for H2 storage on porous materials.

Factors associated with all-cause mortality in patients with coronary artery chronic total occlusions undergoing revascularization (percutaneous coronary intervention or surgery) or medical treatment.

Aim    Chronic total occlusion of a coronary artery (CTO) is a predictor of early and late cardiovascular mortality and poor cardiovascular outcomes in patients with coronary artery disease. The purpose of this study was to identify predictors of all-cause mortality in CTO patients that underwent invasive treatment.Material and methods    Patients between 2012 and 2018 with CTO in at least one vessel, as demonstrated by coronary angiography, were included retrospectively in the study. The patients were divided into two groups, an intervention group (percutaneous and surgical revascularization) and a medical group.Results    A total of 543 patients were studied, 152 females (28%) and 391 males (72%). The median follow-up period was 49 (26-72) mos. A total of 186 (34.2%) patients in the medical group and 357 (65.8%) patients in the invasive therapy group were followed. The 5-yr death rate was observed in 50 (26.9%) patients in the medical group and 53 (14.8%) patients in the intervention group, and it was found to be statistically higher in the medical group (p=0.001). In multivariable analysis, heart failure (odds ratio (OR): 1.92, 95% CI: 1.18-3.14; p=0.01), higher glucose levels (OR: 1.05, 95% CI: 1,02-1.08; p=0.04), lower albumin levels (OR: 0.49, 95% Cl: 0.32-0.72; p=0.001), SYNTAX score (OR: 1.03, 95% CI: 1.01-1.05; p=0.001), and CTO (≥2 occluded artery) (OR: 0.42, 95% CI: 0.22-0.72; p=0.01) were independent factors for all-cause mortality.Conclusion    In comparison to the revascularized group, there was an increase in mortality among CTO patients treated medically. Heart failure, SYNTAX score, albumin, glucose, and CTO (≥2 occluded arteries) were independent risk factors for all-cause mortality.

The effects of melatonin and thymoquinone on doxorubicin-induced cardiotoxicity in rats.

OBJECTIVES: This study aims to investigate the protective effects of thymoquinone and melatonin on the heart against doxorubicin-induced cardiotoxicity in rats. BACKGROUND: Melatonin and thymoquinone may play an important role in cardiotoxicity. METHODS: The subjects were divided into four groups: Control (physiological serum on 5th day), Doxorubicin (DXR), Doxorubicin+Melatonin (DXR+MEL, 10 mg/kg melatonin, intraperitoneally), and Doxorubicin+Thymoquinone (DXR+TQ, 50 mg/kg thymoquinone, orally). On the 5th day of the experiment, all groups were injected with 45 mg/kg DXR into the tail vein. On the 8th day of the experiment, ECG recordings were performed under anaesthesia. RESULTS: Thymoquinone reduced the PR, QRS and QTc intervals, which were increased by DXR, while melatonin only reduced the QTc interval. Melatonin had a protective effect against the histopathological changes induced by DXR, while TQ did not demonstrate such an effect. DXR increased CK-MB, IL-6, MDA, IL-1, IL-18 levels and decreased SOD in the cardiac tissue. MEL reduced the levels of CK-MB, MDA, NO, SOD, IL-1, IL-6, IL-18. Meanwhile, TQ only reduced CK-MB, IL-1 and IL-18. CONCLUSION: Our study showed that DXR induces cardiac injury and that melatonin improves biochemical parameters and offers histological protection; while thymoquinone improves ECG parameters and causes partial recovery of biochemical parameters (Tab. 4, Fig. 2, Ref. 41).

The effect of C-OH functionality on the surface chemistry of biomass-derived molecules: ethanol chemistry on Rh(100).

The adsorption and decomposition of ethanol on Rh(100) was studied as a model reaction to understand the role of C-OH functionalities in the surface chemistry of biomass-derived molecules. A combination of experimental surface science and computational techniques was used: (i) temperature programmed reaction spectroscopy (TPRS), reflection absorption infrared spectroscopy (RAIRS), work function measurements (Kelvin Probe - KP), and density functional theory (DFT). Ethanol produces ethoxy (CH3CH2O) species via O-H bond breaking upon adsorption at 100 K. Ethoxy decomposition proceeds differently depending on the surface coverage. At low coverage, the decomposition of ethoxy species occurs viaß-C-H cleavage, which leads to an oxometallacycle (OMC) intermediate. Decomposition of the OMC scissions (at 180-320 K) ultimately produces CO, H2 and surface carbon. At high coverage, along with the pathway observed in the low coverage case, a second pathway occurs around 140-200 K, which produces an acetaldehyde intermediate viaα-C-H cleavage. Further decomposition of acetaldehyde produces CH4, CO, H2 and surface carbon. However, even at high coverage this is a minor pathway, and methane selectivity is 10% at saturation coverage. The results suggests that biomass-derived oxygenates, which contain an alkyl group, react on the Rh(100) surface to produce synthesis gas (CO and H2), surface carbon and small hydrocarbons due to the high dehydrogenation and C-C bond scission activity of Rh(100).

Normosmic idiopathic hypogonadotropic hypogonadism due to a novel homozygous nonsense c.C969A (p.Y323X) mutation in the KISS1R gene in three unrelated families.

OBJECTIVE: The spectrum of genetic alterations in cases of hypogonadotropic hypogonadism continue to expand. However, KISS1R mutations remain rare. The aim of this study was to understand the molecular basis of normosmic idiopathic hypogonadotropic hypogonadism. METHODS: Clinical characteristics, hormonal studies and genetic analyses of seven cases with idiopathic normosmic hypogonadotropic hypogonadism (nIHH) from three unrelated consanguineous families are presented. RESULTS: One male presented with absence of pubertal onset and required surgery for severe penoscrotal hypospadias and cryptorchidism, while other two males had absence of pubertal onset. Two of four female cases required replacement therapy for pubertal onset and maintenance, whereas the other two had spontaneous pubertal onset but incomplete maturation. In sequence analysis, we identified a novel homozygous nonsense (p.Y323X) mutation (c.C969A) in the last exon of the KISS1R gene in all clinically affected cases. CONCLUSIONS: We identified a homozygous nonsense mutation in the KISS1R gene in three unrelated families with nIHH, which enabled us to observe the phenotypic consequences of this rare condition. Escape from nonsense-mediated decay, and thus production of abnormal proteins, may account for the variable severity of the phenotype. Although KISS1R mutations are extremely rare and can cause a heterogeneous phenotype, analysis of the KISS1R gene should be a part of genetic analysis of patients with nIHH, to allow better understanding of phenotype-genotype relationship of KISS1R mutations and the underlying genetic basis of patients with nIHH.

Assessments of world and national level wrestling teams at a pre world championship competition: hydration, body composition and body mass alterations.

AIM: This study examined the changes in hydration status, body composition and body mass alterations during the camping period a pre world championship, World (N.=14) and National (N.=38) senior wrestlers (N.=52) preparing for the World Championships. METHODS: Urine specific gravity, conductivity and color measurements with, body composition analyses were conducted at the beginning of the camp and the end of the camp. RESULTS: In general, no significant differences were obtained between the world and national wrestlers in body mass and fat percentage (83.3±20-84.9±18 kg; 12±6%-11.2±4%, respectively). However, a significant difference was detected in the changes of body mass between groups (world decreased [800±1 g] - national increased [600±1 g] [P<0.05]). Body fat percentage was also observed to have a similar bias with a decrease and increase, but the changes were not significantly different (P>0.05). No significant differences (P>0.05) were observed between pre- and post-test values of urine specific gravity, conductivity or color for both national team wrestlers. CONCLUSION: Wrestlers achieved to adjust to weight category in a close of period through competition weigh in. Dehydration training programs should be sustained during the whole camp seasons including the last days before the weighing process for matches.

Serum nesfatin-1 levels in overt and subclinical hyperthyroidism.

AIM: Nesfatin-1 was recently discovered anorexigenic peptide in the brain which is derived from nucleobindin-2. Central and peripheral administration of nesfatin-1, inhibits food intake, dose-dependently. Hyperthyroid patients have increased appetite and food intake with a craving for carbohydrate-rich food, at the beginning of disease, but the physiological mechanisms underlying this behavior is not known exactly. In this study, we investigated whether nesfatin-1 is involved in the regulation of appetite and body weight in hyperthyroidism, or not. METHODS: A total of 70 patients with subclinical (35) and overt hyperthyroidism (35) compared with 35 control patients. Serum nesfatin-1 level was measured from all samples by commercial ELISA kit. RESULTS: Serum nesfatin-1 levels were similar between three groups (P=0.293). After adjusting for age and body mass index, nesfatin-1 levels in control group was not different from subclinical and overt hyperthyroid group, respectively (P=0.567 and P=0.519). CONCLUSION: These data showed that serum nesfatin-1 levels do not significant change in overt and subclinical hyperthyroidism.

Predictive effect of nutritional scores assessment for 1-year mortality in patients with severe aortic stenosis treated with SAVR or TAVR.

OBJECTIVE: As treatment modalities of severe AS, interventional treatments such as SAVR or TAVR with the decision of the heart team have been performed recently. Controlling nutritional status (CONUT) score and prognostic nutritional index (PNI) have a very important place among the scores that provide a simple, effective, and objective evaluation of prognosis. In our study, we aimed to investigate the short-term prognostic results of severe AS patients who underwent TAVR or SAVR by comparing the CONUT and PNI results of the patients. PATIENTS AND METHODS: 258 patients who underwent percutaneous TAVR or SAVR in our clinic between December 2012 and December 2020 were included in the study in a randomized retrospective manner. The primary endpoint of the study was in-hospital and 1-year all-cause death. The results of all patient groups were compared by dividing them into 2 groups as all-cause death group (deceased group) and non-all-cause death group (survived group) within 1 year. RESULTS: All-cause mortality occurred in 57 (29%) patients within 1 year. As nutritional status scores, the PNI score (39.9±7.4 vs. 46.5±6.9, p<0.001) was lower in the deceased group and the median CONUT score [4(4) vs. 1(3) p<0.001] was found significantly higher. NLR score was also found to be significantly higher in the deceased group (p<0.001). They were divided into 3 tertiles containing an equal number of patients and compared according to the nutritional scores. Significantly higher 1-year mortality was observed in the high CONUT [10 (12%) deaths in T1, 12 (14%) in T2, and 35 (41%) deaths in T3, respectively, p<0.001] and low PNI [37 (43%) deaths in T1, 13 (15%) in T2, and 7 (8%) deaths in T3, respectively, p<0.001] groups, which can be considered as the worse nutritional group. CONCLUSIONS: In the surgical or transarterial treatment of symptomatic severe aortic stenosis, we found that a high CONUT score and a low PNI score were predictors of all-cause mortality at 1-year follow-up, regardless of the type of treatment. We think that checking patients with scores like the abovementioned procedure and making the necessary corrections will lead to positive results in terms of prognosis.

Prognostic importance of nutritional assessment in patients with acute ischemic stroke undergoing endovascular thrombectomy.

OBJECTIVE: The prevalence of malnutrition in patients with acute ischemic stroke (AIS) can range from 8% to 34%. It has been shown that prognostic nutritional index (PNI) and control nutritional status (CONUT) scores can provide an opportunity to make prognostic predictions in some disease groups. Previous studies have shown a close relationship between malnutrition scores and stroke prognosis. We evaluated the effect of nutritional scores on in-hospital and long-term mortality in AIS patients undergoing endovascular therapy (EVT). PATIENTS AND METHODS: 219 patients who underwent EVT for the AIS were included in this retrospective design and cross-sectional study. The primary endpoint of the study was accepted as all-cause death including in-hospital death, 1-year death, and 3-years death. RESULTS: A total of 57 patients died in the hospital. In-hospital mortality rate was higher in the high CONUT group [36 (49.3%), 10 (13.7%), 11 (15.1%), p<0.001]. A total of 78 patients died within one year, and 1-year mortality was higher in the high CONUT group [43 (58.9%), 21 (28.8), 14 (19.2), p<0.001]. At the end of the 3-year follow-up, 90 patients had died, and the 3-year mortality rate was significantly higher in groups with a high CONUT score than in those with a low CONUT score (p<0.001). CONCLUSIONS: A higher CONUT score, calculated easily by simple scoring with parameters studied from peripheral blood before the EVT procedure, is an independent predictor of in-hospital, 1-year, and 3-years all-cause mortality.

Is NAFLD an independent risk factor for increased IMT in T2DM?

AIM: Recent data have suggested that the presence of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus may also be linked to increased risk of cardiovascular disease (CVD) independent from metabolic syndrome. Therefore the aim of the study is to compare the CVD risk in diabetic and non diabetic participants and to evaluate whether there is an association betweeen NAFLD and CVD risk. METHODS: Fifty five type 2 diabetic (study group) and 44 nondiabetic patients (control group) were included in the study. Patients were divided into two groups according to degree of hepatosteatosis. Group 1 include grade≥2 hepatosteatosis and group 2 include grade<2 hepatosteatosis patients. RESULTS: As a result, hepatosteatosis rates were found to be similar in diabetic and non-diabetic patients (P=0.07). Mean CIMT was significantly higher in diabetic patients (P=0.01). Mean fasting plasma glucose (FPG) and glucolise hemoglobin (HbA1c) were found to be higher in grade≥2 hepatosteatosis group (P=0.002 and 0.004 respectively). But CIMT was found to be similar between hepatosteatosis groups (P=0.618). CONCLUSION: NAFLD is extremely common in people with type 2 diabetes and is mainly associated with uncontrolled diabetes. CIMT values as cardiovascular risk assessment were found to be significantly higher in diabetic patients regardless degree of hepatosteatosis.

A theoretical study of CO adsorption on Cu(211) surface with coverage effects.

CO adsorption on the Cu(211) surface was investigated using energy, geometry and vibrational data, which were produced through periodic DFT computations. Adsorption on the (111) terrace, as well as the previously reported top and bridge sites of the step-edges, was studied at 0.25, 0.33, 0.50, 0.66, 0.75, and 1.00 monolayer (ML) CO coverage. Results showed that up to and including 0.50 ML, on-top or bridge adsorption is preferred on the step-edges. When 0.50 ML is exceeded, top-bridge alternating patterns become feasible on the step edges along with possible shifts towards the terrace. Several feasible patterns were identified at 0.66, 0.75, and 1.00 ML. Like step-edge adsorptions, alternating patterns on the terrace sites were found feasible at higher coverages. For all the studied cases, highest adsorption energies were found for the step-edge positions. In general, coordination number had a stronger effect than coverage on the calculated properties.

Global longitudinal strain score predicts all cause death in patients with chronic total occlusion with preserved ejection fraction.

OBJECTIVE: Change in LVEF is one of the most important indicators of prognosis in CTO cases. Studies in patients with CTO have shown improvement in LVEF approximately at 3 and 6 months after successful PCI. It has been shown that LV global longitudinal strain (GLS) starts to improve even 1 day after CTO-PCI. We aimed at investigating the effect of subclinical echocardiographic involvement on all-cause mortality in the group with CTO and preserved ejection fraction by evaluating the LV GLS score. PATIENTS AND METHODS: Patients with LVEF ≥ 50% were considered to have preserved ejection fraction and were included in the study. The endpoint of the study was all-cause death. For this retrospective study, 1,171 patients with coronary angiography who had had CTO in any of their vessels were screened. RESULTS: A total of 86 consecutive patients were reviewed in the study. The optimum GLS score cut-off value (≥ 14.18) for predicting mortality was determined using receiver operating characteristic (ROC) curve analysis (AUC: 0.897, sensitivity 87.5%, specificity 81.5% p<0.001). At a mean follow-up of 49 months, a significant difference was found between the two groups in all-cause mortality determined by the GLS score [2 (3.4%) vs. 14 (51.9%), p<0.001]. A significant difference in mortality was observed between the group with a low GLS score and the group with a high GLS score, according to Kaplan-Meier analysis. The effect of GLS score in predicting all-cause mortality was demonstrated in multivariate cox regression analysis (Low GLS score; OR: 6.36 95%CI (1.039-39.013), p=0.045). Cox regression multivariate analysis and the effect of GLS score in predicting mortality were observed [Low GLS score; OR: 6.368 95%CI (1.039-39.013), p=0.045]. CONCLUSIONS: As a predictor, GLS may be a valuable marker of cardiac subclinical dysfunction for all caused mortality in CTO patients.

Predictive value of lymphocyte to monocyte ratio for cardiac syndrome X.

OBJECTIVE: Cardiac syndrome X (CSX) is typically described with ischemia in stress tests in addition to angina-like chest pain and without stenosis in coronary angiography. We aimed at determining the relationship between LMR and CSX. PATIENTS AND METHODS: We retrospectively collected patients with CSX between January 2016 and December 2019. Patients with typical angina-like chest pain, normal 12-lead electrocardiography at rest, a positive response to the exercise test (> 0.1 mV ST-segment depression at 80 ms after the J point in two or more contiguous leads) or ischemia on myocardial perfusion scintigraphy and normal coronary angiography were included in the study as CSX patients. RESULTS: This study consisted of 116 patients with CSX and 153 control groups. The mean age of the patients with CSX was 52.7±9.7 years, and the mean age of the control group was 53.7±10.6 years (p= 0.416). The patients with CSX were more likely to have higher monocyte counts and LMR. According to the Pearson correlation test, the CRP value negatively correlated with the LMR. In multivariate logistic regression analysis, LMR remained a significant predictor of CSX. In ROC analysis, LMR < 4.1 had 64% sensitivity and 50% specificity (ROC area under curve: 0.587, 95% CI: 0.519-0.655, p=0.015) in accurately predicting a CSX diagnosis. CONCLUSIONS: We showed that lower LMR levels were associated with the presence of CSX.

Serum heart-type fatty acid binding protein levels in acromegaly patients.

BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is a major cytoplasmic low molecular weight protein and released into the circulation when the myocardium is injured. Previous studies have demonstrated that H-FABP is closely associated with acute coronary syndrome, hypertrophic and dilated cardiomyopathy, heart failure, stroke, obstructive sleep apnea syndrome, and pulmonary embolism. The aim of this study was to investigate serum H-FABP value in patients with acromegaly. METHODS AND RESULTS: We measured serum H-FABP levels in 30 consecutive patients with acromegaly, and 55 age-matched control subjects by using a sandwich enzymelinked immunosorbent assay. Serum H-FABP levels were significantly higher in patients with acromegaly than in control subjects (17.40 ± 10.70, and 8.30 ± 7.20, respectively) (p<0.001). A significant positive correlation was found by Spearman's correlation test between serum H-FABP levels and left ventricular end-systolic diameter (r=0.483, p=0.004). CONCLUSION: Patients with acromegaly have increased levels of H-FABP. Serum H-FABP levels might be a marker of myocardial performance in patients with acromegaly.

Oxidative stress markers are not valuable markers in lean and early age of polycystic ovary syndrome patients.

BACKGROUND: Early atherosclerosis and increased risk of cardiovascular diseases (CVD) have been reported in patients with polycystic ovary syndrome (PCOS). Oxidative stress is an accepted risk factor for the development of CVD. AIM: To evaluate the association between oxidative stress markers [ischemia-modified albumin (IMA), total antioxidant status (TAS), and total oxidant status (TOS) levels], carotid intima- media thickness (CIMT), endocrine and metabolic parameters in patients with PCOS. MATERIALS, SUBJECTS, AND METHODS: We studied 52 patients with PCOS and 36 age- and body mass index (BMI)-matched controls. The diagnosis of PCOS was made according to the Rotterdam criteria. Metabolic, hormonal parameter and IMA, TAS, TOS levels were measured. RESULTS: No statistically significant difference was determined in relation to age, BMI and waist-hip ratio, IMA, TAS, and TOS levels between groups. Mean IMA level was higher in PCOS patients, however, statistical significant difference was not observed. Mean CIMT and homeostasis model assessment of insulin resistance levels were significantly higher in patients with PCOS than in control subjects. CONCLUSION: Our study has shown that although CIMT levels, showing CVD risk, were higher in PCOS patients, TAS and TOS oxidative stress markers were found to be similar between groups, IMA was higher in PCOS patients however the difference was not reach statistical significant. The present results suggest that CIMT increases before the state of ischemia and shows preischemic state of vasculature, while oxidative stress markers are considered to be indicators of ischemia and reperfusion injury in progressive vascular disease. Further studies are needed to show the association between oxidative stress markers, CVD and PCOS.

Wolcott-Rallison syndrome due to the same mutation (W522X) in EIF2AK3 in two unrelated families and review of the literature.

Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disorder characterized by an early-infancy-onset diabetes mellitus associated with a variety of multisystemic clinical manifestations. Here, we present six patients with WRS, carrying the same homozygous mutation (EIF2AK3-W522X), from two unrelated Turkish families. This is the largest series of patients with the same mutation for this rare syndrome. In this communication we compare clinical features of these six patients with the other 34 patients who have been reported to date, and review the clinical features of WRS. All WRS patients presented first with symptoms of insulin dependent diabetes mellitus, with a mean age at onset of 2 months. All patients had skeletal dysplasia or early signs of it, and growth retardation. Many of the patients with WRS have been reported to have developmental delay, mental retardation, and learning difficulties; in contrast, none of our patients showed abnormal development at age up to 30 months. Acute attacks of hepatic failure were reported in 23 cases out of 37 patients; in 15 of those 23 cases an acute attack of renal failure accompanied the liver failure. Exocrine pancreatic deficiency has been reported in only four cases other than our four patients. Central hypothyroidism was observed in six of 28 cases. We propose that central hypothyroidism is not a component of WRS, but rather a reflection of euthyroid sick syndrome. Four of our patients experienced severe neutropenia, compared to only five of the 27 other cases, suggesting that the W522X mutation may be specifically associated with neutropenia. Other than the consistent features of diabetes mellitus and epiphyseal dysplasia, WRS patients are otherwise characterized by extensive phenotypic variability that correlates poorly to genotype.

Exploring the relationship between weaning and infant mortality: an isotope case study from Asikli Höyük and Çayönü Tepesi.

We measured stable nitrogen isotope ratios in bone collagen of 60 individuals from the early Neolithic (9th-8th millennium Cal. BC) sites of Çayönü Tepesi and Asikli Höyük. Our aim was to identify the duration of exclusive breastfeeding (EBF), compare this with juvenile mortality at each site, and assess whether there was a relationship between them. The isotope analysis suggests that weaning commenced at about 1 year at Asikli Höyük and around 2 years at Çayönü Tepesi. The mortality data show equal numbers of infant deaths up to 24 months; however, after 24 months, the mortality rate increases at Çayönü Tepesi, and a Student's t-test confirms a significant difference in infant mortality between the sites. Weaning foods prepared in the early Neolithic from agricultural crops would have had low-iron content, poor nutritional value, and would have been prepared in nonsterilized containers. Therefore, later weaned infants in early Neolithic farming settlements, although capable of some immunological response, were probably undernourished putting them at a disadvantage when encountering bacteria in their weaning food. Our results suggest that infant feeding regimes that introduced infants to weaning foods in the first year of life may have had a positive effect on their survival.