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BACKGROUND:Iron deficiency anemia (IDA) is associated with decreased appetite. The ghrelin hormone is one of the major regulators of appetite. OBJECTIVES:To evaluate appetite and ghrelin levels in patients with IDA, and to investigate the change in appetite and ghrelin following intravenous iron therapy. METHODS:A total of 56 IDA patients and 51 controls were included in the study. Both appetite and ghrelin were assessed at baseline and following intravenous iron therapy. These were assessed at corresponding time intervals in the control group. Appetite was assessed by the SNAQ score (Simplified Nutritional Appetite Questionnaire) and fasting ghrelin levels were assessed by acylated ghrelin (AG), unacylated ghrelin (UAG) and their respective ratio AG/UAG. RESULTS:IDA patients had significantly lower SNAQ scores, yet higher AG levels and higher AG/UAG ratios compared to healthy controls; the mean SNAQ scores were 12.56 ± 3.45 and 16.1 ± 2, respectively (P

Abstract: “Free Zn2+” (rapidly exchangeable Zn2+) is stored along with glutamate in the presynaptic terminals of specific specialized (gluzinergic) cerebrocortical neurons. This synaptically releasable Zn2+ has been recognized as a potent modulator of glutamatergic transmission and as a key toxin in excitotoxic neuronal injury. Surprisingly (despite abundant work on bound zinc), neither the baseline concentration of free Zn2+ in the brain nor the presumed co-release of free Zn2+ and glutamate has ever been directly observed in the intact brain in vivo. Here, we show for the first time in dialysates of rat and rabbit brain and human CSF samples from lumbar punctures that: (i) the resting or “tonic” level of free Zn2+ signal in the extracellular fluid of the rat, rabbit and human being is approximately 19 nM (95% range: 5–25 nM). This concentration is 15,000-fold lower than the “300 μM” concentration which is often used as the “physiological” concentration of free zinc for stimulating neural tissue. (ii) During ischemia and reperfusion in the rabbit, free zinc and glutamate are (as has often been presumed) released together into the extracellular fluid. (iii) Unexpectedly, Zn2+ is also released alone (without glutamate) at a variable concentration for several hours during the reperfusion aftermath following ischemia. The source(s) of this latter prolonged release of Zn2+ is/are presumed to be non-synaptic and is/are now under investigation. We conclude that both Zn2+ and glutamate signaling occur in excitotoxicity, perhaps by two (or more) different release mechanisms. [Copyright &y& Elsevier]

Introduction: Normocalcemic primary hyperparathyroidism is a variant of primary hyperparathyroidism with consistently normal albumin-adjusted or free-ionized calcium levels. It may be an early stage of classic primary hyperparathyroidism or could represent primary kidney or bone disorder characterized by permanent elevation of PTH level., Aim of the Study: The study aims to compare the FGF-23 levels in patients with PHPT, NPHPT, and normal calcium and PTH levels., Methods: Our study included patients who were referred to the endocrinology clinic with a presumptive diagnosis of primary hyperparathyroidism, an isolated increased level of PTH, or reduced bone densitometry. For each patient, we performed blood analysis of FGF-23, calcium, phosphate, vitamin D [25(OH)D3], estimated glomerular filtration rate (eGFR), bone turnover markers, and urine analysis for calcium/creatinine ratio., Results: Our study included 105 patients. Thirty patients with hypercalcemic hyperparathyroidism (HPHPT group), thirty patients with elevated PTH and normal calcium levels (NPHPT group), and 45 patients with normal calcium and PTH levels in the control group. FGF 23 level was 59.5± 23 pg/ml in the NPHPT group, 77 ± 33 pg/ml in the HPHPT group, and 49.7 ± 21.7 pg/ml in the control group (p=0.012). The phosphate level was lowest in the HPHPT group: 2.9 ± 0.6 vs 3.5 ± 0.44 in the NPHPT and 3.8 ± 0.5 in the control groups (p=0.001). No differences were found in eGFR, 25(OH)D3, C-terminal telopeptide type I collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP) levels, and bone densitometry scores between the three study groups., Conclusion: Our findings suggest that NPHPT is an early stage of PHPT. Further studies are needed to determine the role of FGF-23 and its usefulness in NPHPT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chertok Shacham, Maman, Lazareva, Masalha, Mahagna, Sela and Ishay.)

The possible effects of stress and neurobiological stress mechanisms on visuospatial abilities remain largely unknown. In the current study, we examined the combined effect of sex hormones and both the hypothalamic-pituitary-adrenal axis (HPA-A) and the sympathetic nervous system (SNS) on stress-induced changes in visuospatial performance. A total of 107 participants completed a mental rotation task and were subsequently exposed to either to the Trier social stress test (TSST) or to a control condition before completing the mental rotation task again. HPA-A and SNS reactivity of the participants were evaluated by measuring salivary alpha amylase (sAA; an SNS activation marker) and cortisol in four saliva samples. Pre-stress levels of sex hormones (progesterone, estradiol, and testosterone) were also measured. The TSST enhanced mental rotation performance, and this enhancement was negatively correlated with baseline estradiol levels and positively correlated with the level of cortisol reactivity among men. In addition, controlling for baseline levels of testosterone, estradiol, and progesterone diminished this effect of stress. These results imply that the stress-induced facilitation of mental rotation performance is modulated by baseline sex hormones and provide preliminary support to the notion that a complex interaction between sex hormones and neuroendocrine stress mechanisms mediates the influence of stress on visuospatial performance.

The effects of stress on memory performance, and the neuroendocrine mechanisms mediating such effects, are not well understood. Given the interrelationship between reproductive hormones and both the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal axis (HPA-A), we examined their combined effect on stress-induced modulation of declarative memory. Before and after exposure either to the Trier Social Stress Test (TSST) procedure or to a non-stress condition, 112 participants completed the Rey Auditory Verbal Learning Test. We analyzed participants' HPA-A and SNS reactivity by measuring cortisol and salivary alpha-amylase (sAA, an SNS activation marker) in four saliva samples. In addition, testosterone, estradiol, and progesterone were sampled prior to the stress exposure. Exposure to the TSST attenuated memory recall after an introduction of an interference list during the declarative memory task. Importantly, controlling for testosterone, estradiol, and progesterone diminished this effect of stress, suggesting the importance of baseline reproductive hormones in stress-induced modulation of memory functions. Furthermore, a multiple regression model revealed that stress-induced declines in memory performance were negatively associated with participants' stress-induced cortisol reactivity, but only among individuals with high testosterone levels. In addition, stress-induced declines in memory performance were negatively associated with participants' stress-induced increases in sAA, but only in individuals with low progesterone levels. These findings suggest that the effects of stress on memory performance may be modulated by baseline reproductive hormones and provide a preliminary indication for specific modulatory interrelationships between reproductive hormones and neuroendocrine stress mechanisms in mediating the effects of stress on memory., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

While attention deficit hyperactivity disorder (ADHD) has been extensively studied in the past decades, the role of social and cultural practices in its assessment, diagnosis, and treatment has been often overlooked. This selective review provides an overview of research that explores social and cultural influences on help-seeking behavior in ethnic minority children with ADHD. Studies were selected that address cultural diversity in three areas of ADHD help-seeking: problem recognition, access to mental health services, and treatment. Special attention was given to studies of treatment selection and adherence in minority groups. Findings suggested that cultural disparities in ADHD care among ethnic minority children occur in the early stages of problem recognition, through service selection, and in the quality of treatment. Ethnic minority children were less likely than their nonminority counterparts to be diagnosed with ADHD and its comorbid conditions and less likely to be prescribed and adhere to stimulant drug treatment. These differences reflect cultural diversity in norms and attitudes towards mental health issues (e.g., fear of social stigma) as well as limited access to qualified health care. Paradoxically, cultural, racial, and language bias may also lead to the overidentification of ethnic minority children as disabled and to higher ratings of ADHD symptoms. This review highlights the importance of sociocultural factors in understanding developmental psychopathology and help-seeking behavior. In addition, it further supports calls for increasing cultural competence in communications during clinical assessment, diagnosis, and treatment in minority communities. Clinical, theoretical, and methodological considerations for future research are discussed.

Background : Existing theories hold that chronic tobacco smoking leads to the development of adverse psychological symptoms, thus producing a compulsive urge to smoke in order to alleviate these sensations. Sleep disturbances are often considered among the negative consequences of chronic smoking. Objectives : The current study aimed at examining whether dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis may be involved in this disruption of sleep quality among smokers. Methods : Smokers and non-smokers provided saliva samples following awakening for assessment of cortisol concentrations as a measure of HPA activity. Subsequently the participants completed the State-Trait Anxiety Inventory, Brief Questionnaire on Smoking Urges, the Fagerstrom Test for Nicotine Dependence, and the Pittsburgh Sleep Quality Index. Next, their sleep was monitored objectively for one week using an actigraph. Results : While smokers' self-reported sleep quality was similar to that of non-smokers, their sleep recording data pointed to diminished sleep continuity (increased wake time after sleep onset; WASO), while total sleep time and sleep onset latency were similar to that of non-smokers. Cortisol secretion was higher among smokers. However, among smokers only, cortisol was negatively correlated with WASO, suggesting that the direct enhancing effect of smoking on WASO is somewhat balanced by an indirect process related to higher cortisol levels. Possible interpretations for this inconsistent mediation are discussed. Conclusions/Importance : Smoking is associated with reduced sleep continuity and the relationship between smoking and sleep continuity may involve the HPA axis.

Exposure to stress activates both the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). A growing body of research points to the contribution of sex hormones (testosterone, estrogen, and progesterone), the end products of the hypothalamus-pituitary-gonadal (HPG) axis, in modulating stress reactivity. The present study aimed at investigating the potential modulating role of sex hormones on HPA and SNS reactivity to psychosocial stress. The reactivity, induced by the Trier Social Stress Test, was analyzed by measuring the levels of cortisol and alpha-amylase (markers for SNS activity) in four saliva samples each of 21 men and 37 women (17 not using oral contraceptives and in their luteal phase, and 20 women using oral contraceptives). In addition, basal sex hormones were sampled prior to the psychosocial stress exposure. Results revealed that controlling for testosterone, estrogen, and progesterone diminished the impact of stress on cortisol reactivity and on alpha-amylase reactivity. Moreover, controlling for sex hormones also diminished the differential pattern of cortisol reactivity in each experimental group among responders. Furthermore, correlation analyses revealed differences between groups in the association between sex hormones and alpha-amylase. The present findings indicate a modulatory role for sex hormones in HPA and SNS reactivity and emphasize the need for control of sex hormone fluctuations when examining cortisol and alpha-amylase reactivity to stress., (© 2018 Wiley Periodicals, Inc.)

Objective: To identify the clinical characteristics and genetic etiology of a family affected with hereditary spastic paraplegia (HSP)., Methods: Clinical, genetic, and functional analyses involving genome-wide linkage coupled to whole-exome sequencing in a consanguineous family with complicated HSP., Results: A homozygous missense mutation was identified in the ACO2 gene (c.1240T>G p.Phe414Val) that segregated with HSP complicated by intellectual disability and microcephaly. Lymphoblastoid cell lines of homozygous carrier patients revealed significantly decreased activity of the mitochondrial aconitase enzyme and defective mitochondrial respiration. ACO2 encodes mitochondrial aconitase, an essential enzyme in the Krebs cycle. Recessive mutations in this gene have been previously associated with cerebellar ataxia., Conclusions: Our findings nominate ACO2 as a disease-causing gene for autosomal recessive complicated HSP and provide further support for the central role of mitochondrial defects in the pathogenesis of HSP.

Early-onset Parkinson's disease (EOPD) is less common than the typical adult-onset PD and may be associated with a genetic etiology. Mutations in several genes are known to cause autosomal recessive (AR) PD. This study aimed to detect the etiology of EOPD in consanguineous families or families living in a specific small geographic region in Israel. Six families with EOPD affecting more than a single individual were recruited. Homozygous mapping analysis using a single-nucleotide polymorphism-based array was performed in all families, followed by Sanger sequencing of related genes based on the mapping results. In addition, all families underwent PARK2 sequencing and testing for large deletions and duplications in PD-associated genes. Different truncating mutations were detected in the PARK2 gene among affected individuals of three families: c.996C>A (p.Cys332X) and c.101delA in either homozygous or compound heterozygous fashion. Exon 4 deletion was detected in a heterozygous manner in a late-onset PD and in homozygous state in early-onset disease in the same family. No disease-causing mutations were detected in any other tested genes. In total, mutations in the PARK2 gene were detected in four of the six tested families with a history of EOPD. These results further demonstrate the role of PARK2 in AR PD. We recommend genetic analysis for the PARK2 gene when AR PD is suspected.

Objective: To analyze the clinical syndromes and inheritance patterns of multiplex families with epilepsy toward the ultimate aim of uncovering the underlying molecular genetic basis., Methods: Following the referral of families with 2 or more relatives with epilepsy, individuals were classified into epilepsy syndromes. Families were classified into syndromes where at least 2 family members had a specific diagnosis. Pedigrees were analyzed and molecular genetic studies were performed as appropriate., Results: A total of 211 families were ascertained over an 11-year period in Israel. A total of 169 were classified into broad familial epilepsy syndrome groups: 61 generalized, 22 focal, 24 febrile seizure syndromes, 33 special syndromes, and 29 mixed. A total of 42 families remained unclassified. Pathogenic variants were identified in 49/211 families (23%). The majority were found in established epilepsy genes (e.g., SCN1A, KCNQ2, CSTB), but in 11 families, this cohort contributed to the initial discovery (e.g., KCNT1, PCDH19, TBC1D24). We expand the phenotypic spectrum of established epilepsy genes by reporting a familial LAMC3 homozygous variant, where the predominant phenotype was epilepsy with myoclonic-atonic seizures, and a pathogenic SCN1A variant in a family where in 5 siblings the phenotype was broadly consistent with Dravet syndrome, a disorder that usually occurs sporadically., Conclusion: A total of 80% of families were successfully classified, with pathogenic variants identified in 23%. The successful characterization of familial electroclinical and inheritance patterns has highlighted the value of studying multiplex families and their contribution towards uncovering the genetic basis of the epilepsies., (© 2016 American Academy of Neurology.)

Background: The prevalence of Parkinson's disease varies among ethnic and geographic groups around the world, being very low in China and high in Argentina. While the main etiology of the disease has yet to be determined, environmental, occupational and genetic factors seem to play important roles., Objectives: To estimate the prevalence of PD in an Arab Muslim population in Israel, using the drug tracer approach., Methods: We studied a Muslim Arab population living in a well-defined geographic area in Israel, with the majority located in two towns and two large villages. Of the approximately 115,000 residents, about 38% are under the age of 15 and 7.75% are older than 65. Drug tracer methodology was applied in this study. All those who were on anti-PD medication were identified and examined by a neurologist to confirm the diagnosis., Results: The overall crude prevalence of PD in this population was low, 43.24/100,000, while the prevalence in the age group above 65 years was 477.32/100,000. Below this age, the prevalence was very low, 12.29/100,000. PD prevalence was higher in males than in females (ratio 1.17); 63% of male patients smoked cigarettes. The prevalence was found to be twice as high among the residents of rural areas, where most inhabitants work in agriculture., Conclusions: The prevalence of PD among the Arab population in Israel is considered low and comparable to that reported in other Arab countries.

Objective: To describe the first reported case of a seizure in a patient using the dietary supplement DHEA in an attempt to improve ovarian oocyte production., Design: Case report., Setting: University-affiliated teaching hospital, neurologic department., Patient(s): A 30-year-old woman with fragile X syndrome and no history of any convulsive disorder who was receiving IVF treatment., Intervention(s): Daily treatment with the dietary supplement DHEA., Main Outcome Measure(s): Generalized seizure., Result(s): After 1 month of DHEA treatment, the patient was admitted with a generalized seizure., Conclusion(s): A generalized seizure, associated with concurrent intake of DHEA.

Cerebrocortical neurons that store and release zinc synaptically are widely recognized as critical in maintenance of cortical excitability and in certain forms of brain injury and disease. Through the last 20 years, this synaptic release has been observed directly or indirectly and reported in more than a score of publications from over a dozen laboratories in eight countries. However, the concentration of zinc released synaptically has not been established with final certainty. In the present work we have considered six aspects of the methods for studying release that can affect the magnitude of zinc release, the imaging of the release, and the calculated concentration of released zinc. We present original data on four of the issues and review published data on two others. We show that common errors can cause up to a 3000-fold underestimation of the concentration of released zinc. The results should help bring consistency to the study of synaptic release of zinc.

Esterification of fluorescent biosensors is a common strategy used to trap probes within the cell. Zinpyr-1 (ZP1) is a fluorescein-based bright fluorescent sensor for divalent zinc that is cell permeable without prior modification. We describe here the synthesis and characterization of ZP1 sensors containing a carboxylic acid or ethyl ester functionality at the 5 or 6 position of the fluorescein. The presence of an electronegative carboxylate decreases the proton-induced background fluorescence of the probe by lowering the pKa of the benzylic amines responsible for fluorescence quenching. The charged species ZP1(6-CO2-) is membrane-impermeant, whereas the permeability of the neutral ZP1(5/6-CO2Et) is similar to that of the parent sensor. Intracranial microinfusion of ZP1(6-CO2Et) into rat hippocampus produces reduced staining of vesicular zinc in neuropil and very clear delineation of zinc-positive injured neuronal somata and dendrites as compared with ZP1.

Background: Brachioradial pruritus (BRP) is a localized pruritus of the dorsolateral aspect of the arm. BRP is an enigmatic condition with a controversial cause; some authors consider BRP to be a photodermatosis whereas other authors attribute BRP to compression of cervical nerve roots., Objective: We sought to investigate the presence of neuropathy in patients with BRP., Methods: We performed electrophysiologic studies of the median, ulnar, and radial nerves in consecutive patients with BRP, including measurement of sensory and motor distal latency, conduction velocity and F responses of the median and ulnar nerves, and sensory distal latency of the radial nerves in both upper limbs., Results: Included in the study were 7 patients, 5 men and 2 women, with an average age of 58.3 years (range: 42-72 years). Of the patients, 4 (57%) had abnormal F responses that were diagnostic for cervical radiculopathy, and 3 of these patients had prolonged distal latencies of the nerves tested, which may be interpreted as sensory motor neuropathy secondary to chronic radiculopathy. The fourth patient had polyneuropathy secondary to diabetes mellitus., Conclusion: BRP may be attributed to a neuropathy, such as chronic cervical radiculopathy. The possibility of an underlying neuropathy should be considered in the evaluation and treatment of all patients with BRP.