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Hereditary xerocytosis (HX), also known as dehydrated stomatocytosis (DHSt) is a dominantly inherited genetic disorder exhibiting red cell membrane dehydration caused by the loss of the monovalent cation K+ and water. Variants in mechanosensitive Piezo ionic channels of the PIEZO1 gene are the primary cause of HX. We have utilized high throughput and highly precise next-generation sequencing (NGS) to make a diagnosis and examine the genotype-phenotype relationship in inflexible HX cases. Seven unrelated patients with unexplained hemolytic anemia were scrutinized with a panel probing 8000 genes related to congenital anemia. Targeted next-generation sequencing identified 8 missense variants in the PIEZO1 gene in 7 unrelated Indian patients. Three of the 8 variants are novel (c.1795G > C, c.2915G > A, c.7372 T > C) and the remaining five (c.4082A > G, c.6829C > A, c.7374C > G, c.7381G > A, c.7483_7488dup) are previously reported. The variants have been validated by Sanger sequencing. One patient with autosomal dominant mutation (c.7372 T > C) is associated with iron refractory iron deficiency anemia. Of the 7 patients, one has HX in combination with a novel homozygous variant (c.994G > A) in the PKLR gene causing PK deficiency resulting in severe clinical manifestations with phenotypic variability. In silico prediction using bioinformatics tools were used to study the possible damaging effects of the novel variants. Structural-functional analysis of the novel variants was investigated by molecular modeling software (PyMOL and Swiss PDB). These results encompass the heterogeneous behavior of mechano-sensitive Piezo1 protein observed in HX patients in India. Moreover, NGS imparted a subtle, economical, and quick tool for understanding the genetic cause of undiagnosed cases of congenital hemolytic anemia. NGS grants a potential technology integrating clinical history together with molecular report profiting in such patients and their families. [ABSTRACT FROM AUTHOR]

Oral diseases are the major public health problem due to their high prevalence and noteworthy social impact and it can be controlled only if it was diagnosed at an earlier stage. This study is aimed to evaluate oral health status, oral hygiene practices, among 8-10-year-old school going children in Kanchipuram district. A clinical trial was conducted in 90 schools in Kanchipuram district. Students were selected from 3rd, 4th and 5th standard consists of 4 students from each class with a total of 12 students from each school. Dental caries (DMFT and dmft index), brushing frequency, use of fluoridated toothpaste and sugar intake were assessed. Mean decayed permanent teeth and mean decayed milk teeth were found to be 0.29± 0.692 and 2.65± 2.711 respectively. 95.93% of the participants use fluoridated toothpaste and 69.44% brushes once in a day and 30.37% of participants brushes twice a day. Children of 8 years, 9 years and 10 years have 19.2%, 21.8% and 10.6% prevalence of dental caries respectively. Significant association was found between decayed permanent teeth use of fluoridated toothpaste(p=0.001) as children using fluoridated toothpaste had lower prevalence of caries in our clinical trial. [ABSTRACT FROM AUTHOR]

The core criterion for Parkinson's disease dementia (PDD) is the impairment in activities of daily living (ADL) function primarily caused by cognitive, not motor symptoms. There is evidence to assume that mild ADL impairments in mild cognitive impairment (PD‐MCI) characterize those patients at high risk for dementia. Data of 216 Parkinson's disease (PD) patients assessed with comprehensive motor and neuropsychological assessments were analysed. Based on linear regression models, subscores of the Functional Activities Questionnaire (FAQ) primarily reflecting patients' global cognitive status (FAQC) or PD‐related motor severity (FAQM) were developed. A quotient (FAQQ) of both scores was calculated, with values >1 indicating more cognitive‐ compared to motor‐driven ADL impairment. Both FAQC and FAQM scores were higher in PD‐MCI than cognitively normal (PD‐CN) patients, indicating more severe cognitive‐ and motor‐driven ADL impairments in this group. One third (31.6%) of the PD‐MCI group had a FAQQ score >1, which was significantly different from patients with PD‐CN (p =.02). PD‐MCI patients with an FAQQ score >1 were more impaired on tests assessing attention (p =.019) and language (p =.033) compared to PD‐MCI patients with lower FAQQ values. The differentiation between cognitive‐ and motor‐driven ADL is important, as the loss of functional capacity is the defining factor for a diagnosis of PDD. We were able to differentiate the cognitive‐driven from the motor‐driven ADL impairments for the FAQ. PD‐MCI patients with more cognitive‐ compared to motor‐driven ADL impairments may pose a risk group for conversion to PDD and can be targeted for early treatments. [ABSTRACT FROM AUTHOR]

The formation and accumulation of methylglyoxal (MGO), a highly reactive dicarbonyl compound, has been implicated in the pathogenesis of type 2 diabetes, vascular complications of diabetes, and several other age-related chronic inflammatory diseases such as cardiovascular disease, cancer, and disorders of the central nervous system. MGO is mainly formed as a byproduct of glycolysis and, under physiological circumstances, detoxified by the glyoxalase system. MGO is the major precursor of nonenzymatic glycation of proteins and DNA, subsequently leading to the formation of advanced glycation end products (AGEs). MGO and MGO-derived AGEs can impact on organs and tissues affecting their functions and structure. In this review we summarize the formation of MGO, the detoxification of MGO by the glyoxalase system, and the biochemical pathways through which MGO is linked to the development of diabetes, vascular complications of diabetes, and other age-related diseases. Although interventions to treat MGO-associated complications are not yet available in the clinical setting, several strategies to lower MGO have been developed over the years. We will summarize several new directions to target MGO stress including glyoxalase inducers and MGO scavengers. Targeting MGO burden may provide new therapeutic applications to mitigate diseases in which MGO plays a crucial role. [ABSTRACT FROM AUTHOR]

Objective: To evaluate probiotics' effects in reducing hyperbilirubinemia in late preterm and term neonates. Study Design: Quasi-experimental study Place and Duration of Study: Department of Neonatology, Pakistan Institute of Medical Sciences (PIMS), Islamabad Pakistan, from Oct 2018 to Mar 2019. Methodology: The quasi-experimental study was conducted on 60 neonates with hyperbilirubinemia. They were randomly divided into two Groups. Group-A (n=30) received phototherapy. Group-B (n=30) received probiotics containing Lactobacillus reuteri at a dose of 5 drops daily for three days, in addition to phototherapy. Total serum bilirubin was calculated at 0, 24 and 72 hours for both Groups. Results: In Group-A, the mean total bilirubin in mg/dl at 0, 24 and 72 hours were 18.14±2.35, 15.28±2.93 and 12.31±2.29, respectively. Similarly, in Group-B, it was 19.86±5.85, 16.23±4.01 and 10.75±2.23 at 0, 24 and 72 hours, respectively. There was an insignificant statistical difference in mean total bilirubin between Groups A and B at 0 and 24 hours (p<0.001). However, when comparison was made at 72 hours, a significant statistical difference was observed in Group-B (Intervention Group) (p=0.005) Conclusion: Probiotics significantly lowered total serum bilirubin in neonates with hyperbilirubinemia. Further studies are required to evaluate its role in physiological and pathological jaundice. [ABSTRACT FROM AUTHOR]

Objectives: Therapy failure caused by complex population-drug-drug (PDDI) interactions including CYP3A4 can be predicted using mechanistic physiologically-based pharmacokinetic (PBPK) modeling. A synergy between ritonavir-boosted lopinavir (LPVr), ivermectin, and chloroquine was suggested to improve COVID-19 treatment. This work aimed to study the PDDI of the two CYP3A4 substrates (ivermectin and chloroquine) with LPVr in mild-to-moderate COVID-19 adults, geriatrics, and pregnancy populations., Methods: The PDDI of LPVr with ivermectin or chloroquine was investigated. Pearson's correlations between plasma, saliva, and lung interstitial fluid (ISF) levels were evaluated. Target site (lung epithelial lining fluid [ELF]) levels of ivermectin and chloroquine were estimated., Results: Upon LPVr coadministration, while the chloroquine plasma levels were reduced by 30, 40, and 20%, the ivermectin plasma levels were increased by a minimum of 425, 234, and 453% in adults, geriatrics, and pregnancy populations, respectively. The established correlation equations can be useful in therapeutic drug monitoring (TDM) and dosing regimen optimization., Conclusions: Neither chloroquine nor ivermectin reached therapeutic ELF levels in the presence of LPVr despite reaching toxic ivermectin plasma levels. PBPK modeling, guided with TDM in saliva, can be advantageous to evaluate the probability of reaching therapeutic ELF levels in the presence of PDDI, especially in home-treated patients., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

A variety of anatomical alterations have been reported in the hippocampal formation of patients with Alzheimer's Disease (AD) and these alterations have been correlated with cognitive symptoms in the early stages of the disease. Major hallmarks in AD are the presence of paired helical filaments of tau protein (PHFTau) within neurons, also known as neurofibrillary tangles (NFTs), and aggregates of amyloid-β protein (Aβ) which form plaques in the extracellular space. Nevertheless, how the density of plaques and NFTs relate to the severity of cell loss and cognitive decline is not yet clear. The aim of the present study was to further examine the possible relationship of both Aβ plaques and NFTs with neuronal loss in several hippocampal fields (DG, CA3, CA1, and subiculum) of 11 demented AD patients. For this purpose, using stereological techniques, we compared neuronal densities (Nissl-stained, and immunoreactive neurons for NeuN) with: (i) numbers of neurons immunostained for two isoforms of PHFTau (PHFTau-AT8 and PHFTau-pS396); and (ii) number of Aβ plaques. We found that CA1 showed the highest number of NFTs and Aβ plaques, whereas DG and CA3 displayed the lowest number of these markers. Furthermore, AD patients showed a variable neuronal loss in CA1 due to tangle-related cell death, which seems to correlate with the presence of extracellular tangles. [ABSTRACT FROM AUTHOR]

This study aimed to develop a psychometrically valid touch screen tablet-based cognitive test battery to identify early cognitive impairment due to dementia in older adults. The battery includes eight tests with 13 subscores, evaluating visual attention, auditory attention, information processing speed, visual memory, motor control, and visuospatial perception. Among the participants, 43 had been diagnosed with mild cognitive impairment (MCI) and 36 with probable Alzheimer's disease (AD); 41 had no cognitive impairment. The average time to administer the tablet-based tests was 10 minutes. Significant correlations with the Mini-Mental State Examination were found in 9 out of 13 subscores. Patients with probable AD scored significantly lower than controls in 8 out of 13 subscores, whereas those with MCI scored significantly lower in 4 out of 13 subscores. Confirmatory factor analysis using Promax rotation showed that four factors caused lower subscores in the MCI group compared with the controls: information processing speed, memory, visuospatial perception, and motor control. All four factors significantly discriminated the controls from the MCI and probable AD groups, and in the expected direction. The touch screen tablet-based cognitive test battery is psychometrically valid for evaluating cognition in older adults. [ABSTRACT FROM AUTHOR]

Summary: Hereditary erythrocyte membrane disorders are caused by mutations in genes encoding various transmembrane or cytoskeletal proteins of red blood cells. The main consequences of these genetic alterations are decreased cell deformability and shortened erythrocyte survival. Red blood cell membrane defects encompass a heterogeneous group of haemolytic anaemias caused by either (i) altered membrane structural organisation (hereditary spherocytosis, hereditary elliptocytosis, hereditary pyropoikilocytosis and Southeast Asian ovalocytosis) or (ii) altered membrane transport function (overhydrated hereditary stomatocytosis, dehydrated hereditary stomatocytosis or xerocytosis, familial pseudohyperkalaemia and cryohydrocytosis). Herein we provide a comprehensive review of the recent literature on the molecular genetics of erythrocyte membrane defects and their reported clinical consequences. We also describe the effect of low‐expression genetic variants on the high inter‐ and intra‐familial phenotype variability of erythrocyte structural defects. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases share the fact that they derive from altered proteins that undergo an unfolding process followed by formation of β-structures and a pathological tendency to self-aggregate in neuronal cells. This is a characteristic of tau protein in Alzheimer's disease and several tauopathies associated with tau unfolding, α-synuclein in Parkinson's disease, and huntingtin in Huntington disease. Usually, the self-aggregation products are toxic to these cells, and toxicity spreads all over different brain areas. We have postulated that these protein unfolding events are the molecular alterations that trigger several neurodegenerative disorders. Most interestingly, these events occur as a result of neuroinflammatory cascades involving alterations in the cross-talks between glial cells and neurons as a consequence of the activation of microglia and astrocytes. The model we have hypothesized for Alzheimer's disease involves damage signals that promote glial activation, followed by nuclear factor NF-kβ activation, synthesis, and release of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, and IL-12 that affect neuronal receptors with an overactivation of protein kinases. These patterns of pathological events can be applied to several neurodegenerative disorders. In this context, the involvement of innate immunity seems to be a major paradigm in the pathogenesis of these diseases. This is an important element for the search for potential therapeutic approaches for all these brain disorders. [ABSTRACT FROM AUTHOR]

Factor for dementia and pain, the number of patients with both dementia and pain will also grow. Factor for dementia and pain, the number of patients with both dementia and pain will also grow. DM type 2 increases the risk of dementia, in the form of multi-infarct dementia, Alzheimer's Disease/AD and mixed type To dementia severity and comparison in Alzheimer's disease, vascular dementia and frontotemporal dementia. Demographic data, the level of severity in dementia (Mild dementia: OR: 1.81; Moderate dementia: OR: 2.50; Severe. [Extracted from the article]

Objectives: To examine the impacts of changes in social determinants of health (SDH) toward changes in cognition. Methods: Longitudinal data came from the Kanchanaburi Demographic Surveillance System (KDSS) collected in 2007 and 2011. Cognitive impairment was measured by category fluency and delayed recall. Generalized estimating equation (GEE) was used to investigate changes in cognition by taking SDH and other variables including age, gender, marital status, education, and depression into the model. Results: GEE revealed longitudinal effects of wealth index and working status against cognition. Older Thais living with richest wealth index (odds ratio [OR] = 0.54; 95% confidence interval [CI] = 0.31-0.94) and still being employed (OR = 0.65; 95% CI = 0.47-0.89) were less likely to have cognitive impairment. Discussion: Poorer wealth index and being unemployed were served as a risk factor for cognitive impairment over time. Increasing age was still the major risk for cognitive impairment. [ABSTRACT FROM AUTHOR]

Tyrosine hydroxylase (TH), catalyzing the conversion of tyrosine into l‐DOPA, is the rate‐limiting enzyme in dopamine synthesis. Defects in insulin action contribute to alterations of TH expression and/or activity in the brain and insulin increases TH levels in 1‐methyl‐4‐phenylpyridinium (MPP+)‐treated neuronal cells. However, the molecular mechanisms underlying the regulation of TH by insulin have not been elucidated yet. Using PC12 cells, we show for the first time that insulin increases TH expression in a biphasic manner, with a transient peak at 2 hr and a delayed response at 16 hr, which persists for up to 24 hr. The use of a dominant negative hypoxia‐inducible factor 1‐alpha (HIF‐1α) and its pharmacological inhibitor chetomin, together with chromatin immunoprecipitation (ChIP) experiments for the specific binding to TH promoter, demonstrate the direct role of HIF‐1α in the early phase. Moreover, ChIP experiments and transfection of a dominant negative of the nerve growth factor IB (Nur77) indicate the involvement of Nur77 in the late phase insulin response, which is mediated by HIF‐1α. In conclusion, the present study shows that insulin regulates TH expression through HIF‐1α and Nur77 in PC12 cells, supporting the critical role of insulin signaling in maintaining an appropriate dopaminergic tone by regulating TH expression in the central nervous system. Insulin positively regulates tyrosine hydroxylase expression in PC12 cells in a biphasic manner by activating in turn hypoxia‐inducible factor 1‐alpha and nerve growth factor IB. [ABSTRACT FROM AUTHOR]

Background: Extrapyramidal symptoms (EPS) are not uncommon in Alzheimer's disease (AD). As apolipoprotein E(APOE) e4 allele is a major risk factor for late-onset AD, we intend to examine the association between APOE genotype and the development of EPS in AD. Method: This study describes two hundred and fifty-five clinically diagnosed AD patients aged 72 to 80 years from 2010 to 2014. We reviewed the medical charts to determine the development of EPS. APOE genotypes were also confirmed. Results: APOE e4 allele was detected in 74 patients (29%) and rigidity was among the most common EPS (61%). After adjusting the age, gender, baseline clinical dementia rating, we found AD patients carrying APOE e4 allele are more likely to develop EPS (OR: 4.515, p=0.033). Conclusion: This study demonstrates the higher coexistence of EPS in AD patients with APOE e4 allele. Furthermore, the identification of APOE e4 allele in the development of EPS in AD patients supports the hypothesis that EPS may be partially attributed to AD pathology. [ABSTRACT FROM AUTHOR]

Objectives: Impairments in the Boston Naming Test (BNT), which measures confrontational word retrieval, frequently accompanies Alzheimer's dementia (AD) and may predict a more rapid progression of illness. This study aims to validate the Thai version of the 15-item BNT (T-BNT) in participants with AD and amnestic mild cognitive impairment (aMCI) and to externally validate the T-BNT using clinical and biomarker measurements. Methods: This cross-sectional study recruited patients with AD, diagnosed according to NINCDS-ADRDA criteria (n = 60), aMCI, diagnosed using the Petersen criteria (n = 60), and healthy controls (n = 62). We examined the internal consistency, concurrent and discriminant reliability of the T-BNT. We also assessed the Mini Mental State Examination (MMSE), the Verbal Fluency Test (VFT) and the Word List Memory (WLM) tests and measured apolipoprotein E polymorphism and serum levels of folic acid, high-density lipoprotein cholesterol (HDL) and triglycerides. Results: This study validated a 10-item T-BNT (10T-BNT), which yielded good internal consistency (0.92), a one-factor unidimensional structure, and adequate concurrent and discriminant validity. Lower scores on the 10T-BNT highly significantly predict AD, but not aMCI, and are positively associated with VFT and WLM test scores. Furthermore, lowered 10T-BNT scores are significantly associated with the ApoE4 allele, lower folate levels and an increased triglyceride/HDL-cholesterol ratio. Conclusions: This study validated the 10T-BNT and the total score on this scale is strongly associated with AD, impairments in semantic and episodic memory and biomarkers, which are known to modify memory via different mechanisms. [ABSTRACT FROM AUTHOR]

Background: Bronchiectasis is associated with morbidity, low exercise capacity and poor quality of life. There is a paucity of data on exercise capacity using cardiopulmonary exercise test (CPET) in non-cystic fibrosis (CF) bronchiectasis. Our aim was to compare exercise capacity using CPET in CF and non-CF bronchiectasis patients. Methods: Cross-sectional retrospective/prospective controlled study assessing CPET using cycle ergometer. Exercise parameters and computed tomography (CT) findings were compared. Results: Hundred two patients with bronchiectasis and 88 controls were evaluated; 49 CF (age 19.7 ± 9.7 y/o, FEV1%predicted 70.9 ± 20.5%) and 53 non-CF (18.6 ± 10.6 y/o, FEV1%predicted 68.7 ± 21.5%). Peak oxygen uptake (peak ) was similar and relatively preserved in both groups (CF 1915.5±702.0; non-CF 1740±568; control 2111.0±748.3 mL/min). Breathing limitation was found in the two groups vs. control; low breathing reserve (49% in CF; 43% non-CF; 5% control) and increased (CF 31.4±4.1, non-CF 31.7±4.1 and control 27.2 ± 2.8). Oxygen pulse was lower in the non-CF; whereas a linear relationship between peak vs. FEV1 and vs. FVC was found only for CF. CT score correlated with and negatively correlated with and post exercise oxygen saturation (SpO2). Conclusions: CPET parameters may differ between CF and non-CF bronchiectasis. However, normal exercise capacity may be found unrelated to the etiology of the bronchiectasis. Anatomical changes in CT are associated with functional finding of increased and decreased SpO2. Larger longitudinal studies including cardiac assessment are needed to better study exercise capacity in different etiologies of non-CF bronchiectasis. Trial registration: ClinicalTrials.gov, registration number: . [ABSTRACT FROM AUTHOR]

Cognitive impairment is associated with various chronic diseases, including mobility limitation and early mortality. Thus, evaluating changes in cognition is of paramount public health interest. The purpose of this study was to evaluate secular trends in cognitive function among a representative sample of the U.S. older adult population. Data from the 1999–2000, 2001–2002, 2011–2012, and 2013–2014 National Health and Nutrition Examination Survey were utilized to identify an aggregate sample of adults 60+ years of age. The sample size across the four respective cycles was 1417, 1558, 1422, and 1592. Three cognitive assessments were employed, including the CERAD Word Learning subset (Consortium to Establish a Registry for Alzheimer's disease), the Animal Fluency test, and the Digit Symbol Substitution Test (DSST). For the entire sample and several subpopulations, DSST scores increased from 1999 to 2012 and then decreased in the 2013 to 2014 cycle. For all CERAD trials, there was evidence of increased CERAD performance from 2011–2012 to 2013–2014. No secular trends were observed for the Animal Fluency task across these cycles. Select cognitive parameters appear to be improving among U.S. older adults. Future work is needed to further explore secular trends in cognitive sustainability, and, as evidenced by our present study, cognitive enrichment over time. [ABSTRACT FROM AUTHOR]

Summary: Iron overload (IO) is poorly investigated in the congenital haemolytic anaemias (CHAs), a heterogeneous group of rare inherited diseases encompassing abnormalities of the erythrocyte membrane and metabolism, and defects of the erythropoiesis. In this study we systematically evaluated routine iron parameters and cardiac and hepatic magnetic resonance imaging, together with erythropoietin, hepcidin, non‐transferrin bound iron (NTBI), and cytokine serum levels in patients with different CHAs. We found that 40% of patients had a liver iron concentration (LIC) >4 mg Fe/g dry weight. Hepatic IO was associated with ferritin levels (P = 0·0025), transferrin saturation (TfSat, P = 0·002) and NTBI (P = 0·003). Moreover, ferritin >500 μg/l plus TfSat >60% was demonstrated as the best combination able to identify increased LIC, and TfSat alteration as more important in cases with discordant values. Possible confounding factors, such as transfusions, hepatic disease, metabolic syndrome and hereditary haemochromatosis‐associated mutations, had negligible effects on IO. Erythropoietin and hepcidin levels were increased in CHAs compared with controls, correlating with LIC and ferritin, respectively. Regarding cytokines, γ‐interferon (IFN‐γ) was increased, and both interleukin 6 and IFN‐γ levels positively correlated with ferritin and hepcidin levels. Overall, these findings suggest the existence of a vicious cycle between chronic haemolysis, inflammatory response and IO in CHAs. [ABSTRACT FROM AUTHOR]

Aim. To study the prevalence of cognitive and emotional impairment following a minor ischemic stroke compared to an age-matched group with non-ST-elevation myocardial infarction (NSTEMI). Methods. We included patients aged 18-70 years with a minor ischemic stroke defined as modified Rankin Scale (mRS) 0-2 at day 7 or at discharge if before and age-matched NSTEMI patients with the same functional mRS. We applied a selection of cognitive tests and the patients completed a questionnaire comprising of Hospital Anxiety and Depression scale (HADS) and Fatigue Severity Scale (FSS) at follow-up 12 months after the vascular event. Results of cognitive tests were also compared to normative data. Results. 325 ischemic stroke and 144 NSTEMI patients were included. There was no significant difference in cognitive functioning between ischemic stroke and NSTEMI patients. Minor stroke patients and to a lesser extent NSTEMI patients scored worse on more complex cognitive functions including planning and implementation of activities compared to validated normative data. For the minor stroke patients the location of the ischemic lesion had no influence on the result. The prevalence of anxiety, depression, and fatigue was significantly higher in the stroke group compared to the NSTEMI group. Depression was independently associated with reduced cognitive function. Discussion and Conclusion. Minor ischemic stroke patients, and to lesser degree NSTEMI patients, had reduced cognitive function compared to normative data, especially executive functioning, on 12-month follow-up. The difference in cognitive function between stroke and NSTEMI patients was not significant. Depression was associated with low scores on cognitive tests highlighting the need to adequately address emotional sequelae when considering treatment options for cognitive disabilities. [ABSTRACT FROM AUTHOR]

Background/Objective: In recent years, several slightly younger cohorts have been established in order to study the preclinical and prodromal phases of dementia. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) wordlist memory test (WLT) is widely used in dementia research. However, culturally adapted and demographically adjusted test norms for younger ages are lacking. Method: This paper investigates effects of age, gender and years of education on test performance and offers demographically adjusted norms for the CERAD WLT using a regression-based norming procedure for the age span 40–80 years based on healthy controls (n = 227) from the Norwegian "Dementia Disease Initiation" (DDI) (n = 168) and "Trønderbrain" (n = 59) cohorts. In order to evaluate normative performance, we apply the norms to an independent sample of persons diagnosed with mild cognitive impairment (MCI = 168) and perform multiple regression analyses to evaluate adjustment of pertinent demographics. Results: CERAD WLT norms adjusted for effects of age, gender and educational level are proposed. The norms successfully adjusted for effects of age, gender and education in an independent sample of Norwegians with MCI. Conclusion: Demographically adjusted norms for the CERAD WLT for ages 40–80 years based on a Norwegian sample are proposed. To our knowledge, this is the first normative study of this test to offer demographically adjusted norms for this age span. [ABSTRACT FROM AUTHOR]

The synthesis of a [2]rotaxane, comprising a calix[6]arene-wheel and a dibenzyl-ammonium axle, is here reported. By virtue of its inherent directionality, the calix-wheel makes non-degenerate two equivalent stations of the symmetrical axle. In this way, the neutral rotaxane shows two co-conformations, named endo-alkyl and endo-benzyl, in which an alkyl or benzyl moiety of the axle are included inside the calix-cavity, respectively. NMR and DFT studies showed that the co-conformation preferred by the neutral mechanomolecule is the ‘endo-alkyl’ one, which is more stabilized by C-H···π interactions between the included alkyl chain and the aromatic wall of the calix-cavity. [ABSTRACT FROM AUTHOR]

We study correlations between Madelung constants, charges of surface ions, and chemical activity of low-coordinated sites of the MgO crystal surface with respect to dissociative adsorption of hydrogen. The ab initio Embedded Cluster model [Puchin et al., Phys. Rev. B 47, 6226 (1993)] employed in this study allowed us to reproduce correctly both short range and long range (Madelung) parts of the interaction between ions in a quantum cluster and the rest of the crystal. Our results show that sites having the same coordination numbers may have different properties, depending on values of Madelung constants. Lower Madelung constants correspond to lower ionicity, higher energy of H2 adsorption, stronger O–H and Mg–H bonds, and larger spatial separation of two adsorbed hydrogen atoms. © 1995 American Institute of Physics. [ABSTRACT FROM AUTHOR]

An ab initio study is presented concerning the chemisorption of hydrogen on a model of the (100) surface of MgO and Li-doped MgO. The local surface environment was modeled employing cubic and tetragonal clusters composed of 8 and 12 atoms, respectively. The lattice constant for the clusters was fixed at the experimentally determined value for bulk MgO and the geometry of the adsorbate was optimized at the unrestricted Hartree–Fock (UHF) level of theory. Correlation energy was treated at the second-order unrestricted Mo\ller–Plesset (UMP2) level at the UHF optimized geometry. It was found that H2 undergoes heterolytic dissociation at neighboring three-coordinated Mg and O sites (denoted Mg3c and O3c) in MgO with activation energies of 4.2 and 2.4 kcal/mol at the UHF and UMP2 levels, respectively. Li-doped MgO did not support heterolytic dissociation at neighboring Mg and O sites. Instead H2 was found to dissociate homolytically without barrier at two O3c sites and to undergo hydrogen atom abstraction at O3c and O4c sites. At the UHF/UMP2 level, it was found that at O3c sites, abstraction occurs with a 17.9/3.0 kcal/mol barrier, and at O4c sites, abstraction occurs with a 15.7/0.6 kcal/mol activation energy. [ABSTRACT FROM AUTHOR]

Background: The French West-Indies rank first for both prostate cancer incidence and mortality rates. Analyzing diagnostic and therapeutic procedures among patients with prostate cancer, using data from a population-based cancer registry, is essential for cancer surveillance and research strategies.Methods: This retrospective observational cohort study was based on data from the Martinique Cancer Registry. Records of 452 patients diagnosed with prostate cancer in 2013 were retrieved from the registry. Data extracted were: socio-demographic and clinical characteristics, circumstances of diagnosis, PSA level at diagnosis, Gleason score and risk of disease progression. Stage at diagnosis and patterns of care among prostate cancer patients were analyzed.Results: Mean age at diagnosis was 67 ± 8 years; 103 (28.5%) were symptomatic at diagnosis. Digital rectal exam was performed in 406 (93.8%). Clinical stage was available in 385 (85.2%); tumours were localized in 322/385 (83.6%). Overall, 17.9% were at low risk, 36.4% at intermediate and 31.9% at high risk; 13.8% were regional/metastatic cancers. Median PSA level at diagnosis was 8.16 ng/mL (range 1.4-5000 ng/mL). A total of 373 patients (82.5%) received at least one treatment, while 79 (17.5%) had active surveillance or watchful waiting. Among patients treated with more than one therapeutic strategy, the most frequent combination was external radiotherapy with androgen deprivation (n = 102, 22.6%).Conclusions: This study provides detailed data regarding the quality of diagnosis and management of patients with prostate cancer in Martinique. Providing data on prostate cancer is essential for the development of high-priority public health measures for the Caribbean. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the prognostic factors of recurrence in uterine tumors resembling ovarian sex-cord tumors (UTROSCT) and to determine clinical-pathological characteristics, treatment options and outcome. Material and Method: An electronic literature search was conducted from 1976 to 2018. After the comprehensive evaluation and conjunction with our case, the study included 79 cases. Results: The median age at initial diagnosis was 49 years (range; 16-86 years). The age was under 40 years in 21 (26.6%) patients. Whereas 68 patients underwent at least hysterectomy, 9 patients had organ sparing surgery. There was necrosis in 4 (5.1%) patients, atypia in 16 (20.3%) patients, and infiltrative tumor border in 34 (43%) patients. At least one mitosis per 10 high power fields was determined in 36 (45.5%) patients. The tumor involved at least part of the myometrium in 54 (68.3%) patients. Median follow-up time was 30 months (range; 3-296 months). Recurrence was determined in 5 (6.3%) patients. The disease free survival (DFS) was significantly related only to surgery type. None of the pathologic features were associated with DFS. The 5-year DFS was 86% and 96% in patients who underwent organ sparing surgery or not, respectively (p=0.038). Conclusion: The accurate pathologic diagnosis of UTROSCT has great value in shaping surgical management and management during the follow-up period. Organ sparing surgery was related to poor DFS. Although recurrence is rare, it should be kept in mind for patients with UTROSCT. [ABSTRACT FROM AUTHOR]

Purpose Recording cancer data in cancer registries is essential for producing reliable population-based data for service planning, monitoring and evaluation. Prostate cancer (PCa) remains the most frequent type of cancer in terms of incidence and mortality in men in the Caribbean. The quality of life PCa cohort will assess quality of life and patient outcomes in Martinique using a digital platform for patient-reported outcome measures. Participants The Martinique Cancer Registry database is the largest clinical database among the French population-based cancer registries in the Caribbean, including more than 38 000 cancer cases, with 1650 new cancer cases per year, including 550 new PCa cases per year (2010-2014 latest period). In 2018, follow-up will include vital status, assessment of quality of life with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ) Core 30 and the Prostate cancer module QLQ-PR25. Urinary incontinence and erectile dysfunction recorded prior to treatment will be analysed 1 and 5 years after treatment. Findings to date The registry includes data on circumstances of diagnosis, clinical stage at diagnosis. For PCa, the registry includes blood prostate-specific antigen level at the time of diagnosis, Gleason score and primary treatment. Future plans Further studies will provide detailed data regarding the quality of diagnosis and management of patients with PCa in Martinique; analysing quality of care will be the next challenge. Quality of life and patient outcomes will be evaluated using a digital platform for patient-reported outcome measurement and electronic records. [ABSTRACT FROM AUTHOR]

The synthesis of new calix[6]arene derivatives bearing anthracenyl and naphthyl fluorescent units at the lower rim is here reported. The threading abilities of these new derivatives toward dialkylammonium and bis(benzylalkylammonium) axles were investigated by NMR and fluorescence spectroscopy. A quenching of the fluorescence of the calix-wheels was observed upon threading with ammonium axles. Finally, DFT calculations evidenced that stabilizing C-H···π interactions are present between the axle and the anthracenyl or naphthyl group of the wheel, in addition to the usual H-bond interactions between the ammonium group of the axle and the oxygen atoms of the calix-wheel. [ABSTRACT FROM AUTHOR]

Periodontal health is defined by absence of clinically detectable inflammation. There is a biological level of immune surveillance that is consistent with clinical gingival health and homeostasis. Clinical gingival health may be found in a periodontium that is intact, i.e. without clinical attachment loss or bone loss, and on a reduced periodontium in either a non‐periodontitis patient (e.g. in patients with some form of gingival recession or following crown lengthening surgery) or in a patient with a history of periodontitis who is currently periodontally stable. Clinical gingival health can be restored following treatment of gingivitis and periodontitis. However, the treated and stable periodontitis patient with current gingival health remains at increased risk of recurrent periodontitis, and accordingly, must be closely monitored. Two broad categories of gingival diseases include non‐dental plaque biofilm–induced gingival diseases and dental plaque‐induced gingivitis. Non‐dental plaque biofilm‐induced gingival diseases include a variety of conditions that are not caused by plaque and usually do not resolve following plaque removal. Such lesions may be manifestations of a systemic condition or may be localized to the oral cavity. Dental plaque‐induced gingivitis has a variety of clinical signs and symptoms, and both local predisposing factors and systemic modifying factors can affect its extent, severity, and progression. Dental plaque‐induced gingivitis may arise on an intact periodontium or on a reduced periodontium in either a non‐periodontitis patient or in a currently stable "periodontitis patient" i.e. successfully treated, in whom clinical inflammation has been eliminated (or substantially reduced). A periodontitis patient with gingival inflammation remains a periodontitis patient (Figure 1), and comprehensive risk assessment and management are imperative to ensure early prevention and/or treatment of recurrent/progressive periodontitis. Precision dental medicine defines a patient‐centered approach to care, and therefore, creates differences in the way in which a "case" of gingival health or gingivitis is defined for clinical practice as opposed to epidemiologically in population prevalence surveys. Thus, case definitions of gingival health and gingivitis are presented for both purposes. While gingival health and gingivitis have many clinical features, case definitions are primarily predicated on presence or absence of bleeding on probing. Here we classify gingival health and gingival diseases/conditions, along with a summary table of diagnostic features for defining health and gingivitis in various clinical situations. [ABSTRACT FROM AUTHOR]

Abstract: Periodontal health is defined by absence of clinically detectable inflammation. There is a biological level of immune surveillance that is consistent with clinical gingival health and homeostasis. Clinical gingival health may be found in a periodontium that is intact, i.e. without clinical attachment loss or bone loss, and on a reduced periodontium in either a non‐periodontitis patient (e.g. in patients with some form of gingival recession or following crown lengthening surgery) or in a patient with a history of periodontitis who is currently periodontally stable. Clinical gingival health can be restored following treatment of gingivitis and periodontitis. However, the treated and stable periodontitis patient with current gingival health remains at increased risk of recurrent periodontitis, and accordingly, must be closely monitored. Two broad categories of gingival diseases include non‐dental plaque biofilm–induced gingival diseases and dental plaque‐induced gingivitis. Non‐dental plaque biofilm‐induced gingival diseases include a variety of conditions that are not caused by plaque and usually do not resolve following plaque removal. Such lesions may be manifestations of a systemic condition or may be localized to the oral cavity. Dental plaque‐induced gingivitis has a variety of clinical signs and symptoms, and both local predisposing factors and systemic modifying factors can affect its extent, severity, and progression. Dental plaque‐induced gingivitis may arise on an intact periodontium or on a reduced periodontium in either a non‐periodontitis patient or in a currently stable “periodontitis patient” i.e. successfully treated, in whom clinical inflammation has been eliminated (or substantially reduced). A periodontitis patient with gingival inflammation remains a periodontitis patient (Figure 1), and comprehensive risk assessment and management are imperative to ensure early prevention and/or treatment of recurrent/progressive periodontitis. Precision dental medicine defines a patient‐centered approach to care, and therefore, creates differences in the way in which a “case” of gingival health or gingivitis is defined for clinical practice as opposed to epidemiologically in population prevalence surveys. Thus, case definitions of gingival health and gingivitis are presented for both purposes. While gingival health and gingivitis have many clinical features, case definitions are primarily predicated on presence or absence of bleeding on probing. Here we classify gingival health and gingival diseases/conditions, along with a summary table of diagnostic features for defining health and gingivitis in various clinical situations. [ABSTRACT FROM AUTHOR]

The main pathological hallmarks in Alzheimer's disease (AD) are the presence of extracellular amyloid plaques, primarily consisting of amyloid-β (Aβ) peptide, and the accumulation of paired helical filaments of hyperphosphorylated tau protein (PHF-Tau) within neurons. Since CA1 is one of the most affected regions in AD, mainly at early stages, we have performed a detailed analysis of the CA1 region from 11 AD patients (demented and clinically similar; Braak stages IV-VI) to better understand the possible relationship between the presence and distribution of different neurochemical types of Aβ plaques and PHF-Tau immunoreactive  (- ir)  neurons. Hence, we have examined hippocampal sections in confocal microscopy images from double and triple-immunostained sections, to study labeled plaques and PHF-Tau-ir neurons using specific software tools. There are four main findings in the present study. First, the pyramidal layer of proximal CA1 (close to CA2) contains the smallest number of both plaques and PHF-Tau-ir neurons. Second, a large proportion of Aβ-ir plaques were also characterized by the presence of PHF-Tau-ir. Third, all plaques containing one of the two PHF-Tau isoforms also express the other isoform, that is, if a plaque contains PHFpS396, it also contains PHFAT8, and vice versa. Fourth, the coexpression study of both PHF-Tau isoforms in CA1 neurons revealed that most of the labeled neurons express only PHFpS396. Our findings further support the idea that AD is not a unique entity even within the same neuropathological stage, since the microanatomical/neurochemical changes that occur in the hippocampus greatly vary from one patient to another. [ABSTRACT FROM AUTHOR]

A 74 year-old woman (MD), free of previous neurological history, presented with difficulty in handling cutlery, clothes, writing with what was initially described as an atypical apraxia in acts related to space. Initial neurological evaluation revealed mixed, asymmetric pyramidal, and extrapyramidal semiology. Νeuropsychological testing revealed dressing and constructional deficits, ideomotor apraxia and signs of executive dysfunction in absence of memory, language, and visual perception pathology. The final diagnosis was that of a corticobasal degeneration, where the rare occurrence of a progressively emerging syndrome of self-management loss within peripersonal space is observed. [ABSTRACT FROM AUTHOR]

Primary ciliary dyskinesia (PCD) restricts lifestyle and increases morbidity. The aim of the study was to investigate anaerobic and aerobic performance in children with PCD and their healthy counterparts. Thirty-one children with PCD and 29 age- and sex-matched healthy subjects were studied. Pulmonary function, hand grip strength (HGS), quadriceps strength (QMS), physical activity, anaerobic capacity (muscle power sprint test), and aerobic performance (modified shuttle walk test (MSWT)) were determined. Pulmonary function, HGS, QMS, mean anaerobic power (MAP), and MSWT distance in PCD were significantly lower than those of healthy subjects (p < 0.05). In PCD, the MAP was significantly correlated with age, FEV1, and the mean kcal for 3 days (p < 0.05), and age was its independent predictor (p < 0.05). The MSWT distance was significantly related to gender and weight (p < 0.05), and gender was selected as its independent predictor (p < 0.05). In healthy controls, the MAP was significantly associated with age, gender, FVC, FEV1, HGS, QMS, and the mean kcal for three days (p < 0.05). The MSWT distance was significantly related to weight and body mass index in healthy group (p < 0.05).Conclusion: Anaerobic and aerobic performance is impaired in PCD from the early stages. Age determines anaerobic performance. Gender is the determinant of aerobic performance. Whether skeletal muscle characteristics and sex-related changes in body composition affect anaerobic and aerobic capacity in PCD children warrants further study. What is Known: • Exercise performance is determined by anaerobic and aerobic power. • Few studies have shown that PCD patients have lower aerobic performance which is associated with impaired lung function. What is New: • The present research indicated that both anaerobic and aerobic exercise capacity determined using field testing is impaired in PCD from the early stages. • Anaerobic capacity was found to be independently associated with age in PCD. Higher aerobic performance is independently associated with male gender. [ABSTRACT FROM AUTHOR]

Progressive neurodegenerative pathologies in aged populations are an issue of major concern worldwide. The microtubule-associated protein tau is able to self-aggregate to form abnormal supramolecular structures that include small oligomers up to complex polymers. Tauopathies correspond to a group of diseases that share tau pathology as a common etiological agent. Since microglial cells play a preponderant role in innate immunity and are the main source of proinflammatory factors in the central nervous system (CNS), the alterations in the cross-talks between microglia and neuronal cells are the main focus of studies concerning the origins of tauopathies. According to evidence from a series of studies, these changes generate a feedback mechanism reactivating microglia and provoking constant cellular damage. Thus, the previously summarized mechanisms could explain the onset and progression of different tauopathies and their functional/behavioral effects, opening the window towards an understanding of the molecular basis of anomalous tau interactions. Despite clinical and pathological differences, increasing experimental evidence indicates an overlap between tauopathies and synucleinopathies, considering that neuroinflammatory events are involved and the existence of protein misfolding. Neurofibrillary tangles of pathological tau (NFT) and Lewy bodies appear to coexist in certain brain areas. Thus, the co-occurrence of synucleinopathies with tauopathies is evidenced by several investigations, in which NFT were found in the substantia nigra of patients with Parkinson's disease, suggesting that the pathologies share some common features at the level of neuroinflammatory events. [ABSTRACT FROM AUTHOR]

Abstract: There is an increasing incidence of well‐differentiated thyroid cancer worldwide. Much of the increase is secondary to increased detection of small, low‐risk tumors, with questionable clinical significance. This review addresses the factors that contribute to the increasing incidence and considers environmental, and patient‐based and clinician‐led influences. Articles addressing the causes of the increased incidence were critically reviewed. A complex interplay of environmental, medical, and social pressures has resulted in increased awareness of the thyroid disease risk, increased screening of thyroid cancers, and increased diagnosis of thyroid cancers. Although there is evidence to suggest that the true disease incidence may be changing slightly, most of the increase is related to factors that promote early diagnosis of low‐risk lesions, which is resulting in a significant phenomenon of overdiagnosis. An improved understanding of these pressures at a global level will enable healthcare policymakers to react appropriately to this challenge in the future. [ABSTRACT FROM AUTHOR]

Metabolic and/or endocrine dysfunction of the white adipose tissue (WAT) contribute to the development of metabolic disorders, such as Type 2 Diabetes (T2D). Therefore, the identification of products able to improve adipose tissue function represents a valuable strategy for the prevention and/or treatment of T2D. In the current study, we investigated the potential effects of dry extracts obtained from Citrus aurantium L. fruit juice (CAde) on the regulation of 3T3-L1 cells adipocyte differentiation and function in vitro. We found that CAde enhances terminal adipocyte differentiation of 3T3-L1 cells raising the expression of CCAAT/enhancer binding protein beta (C/Ebpβ), peroxisome proliferator activated receptor gamma (Pparγ), glucose transporter type 4 (Glut4) and fatty acid binding protein 4 (Fabp4). CAde improves insulin-induced glucose uptake of 3T3-L1 adipocytes, as well. A focused analysis of the phases occurring in the pre-adipocytes differentiation to mature adipocytes furthermore revealed that CAde promotes the early differentiation stage by up-regulating C/ebpβ expression at 2, 4 and 8 h post the adipogenic induction and anticipating the 3T3-L1 cell cycle entry and progression during mitotic clonal expansion (MCE). These findings provide evidence that the exposure to CAde enhances in vitro fat cell differentiation of pre-adipocytes and functional capacity of mature adipocytes, and pave the way to the development of products derived from Citrus aurantium L. fruit juice, which may improve WAT functional capacity and may be effective for the prevention and/or treatment of T2D. [ABSTRACT FROM AUTHOR]

Recent rapid growth of the world's population has increased food demands. This phenomenon poses a great challenge for food manufacturers in maximizing the existing food or plant resources. Nowadays, the recovery of health benefit bioactive compounds from fruit wastes is a research trend not only to help minimize the waste burden, but also to meet the intensive demand from the public for phenolic compounds which are believed to have protective effects against chronic diseases. This review is focused on polyphenolic compounds recovery from tropical fruit wastes and its current trend of utilization. The tropical fruit wastes include in discussion are durian (Durio zibethinus), mangosteen (Garcinia mangostana L.), rambutan (Nephelium lappaceum), mango (Mangifera indica L.), jackfruit (Artocarpus heterophyllus), papaya (Carica papaya), passion fruit (Passiflora edulis), dragon fruit (Hylocereus spp), and pineapple (Ananas comosus). Highlights of bioactive compounds in different parts of a tropical fruit are targeted primarily for food industries as pragmatic references to create novel innovative health enhancement food products. This information is intended to inspire further research ideas in areas that are still under-explored and for food processing manufacturers who would like to minimize wastes as the norm of present day industry (design) objective. [ABSTRACT FROM PUBLISHER]

This article describes the complex interactions occurring between diet, the gut microbiome, and bile acids in the etiology of fatty liver disease. Perhaps 25% of the world's population may have nonalcoholic fatty liver disease (NAFLD) and a significant percentage (∼20%) of these individuals will progress to nonalcoholic steatohepatitis (NASH). Currently, the only recommended treatment for NAFLD and NASH is a change in diet and exercise. A Western-type diet containing high fructose corn syrup, fats, and cholesterol creates gut dysbiosis, increases intestinal permeability and uptake of LPS causing low-grade chronic inflammation in the body. Fructose is a "lipogenic" sugar that induces long-chain fatty acid (LCFA) synthesis in the liver. Inflammation decreases the oxidation of LCFA, allowing fat accumulation in hepatocytes. Hepatic bile acid transporters are downregulated by inflammation slowing their enterohepatic circulation and allowing conjugated bile acids (CBA) to increase in the serum and liver of NASH patients. High levels of CBA in the liver are hypothesized to activate sphingosine-1-phosphate receptor 2 (S1PR2), activating pro-inflammatory and fibrosis pathways enhancing NASH progression. Because inflammation appears to be a major physiological driving force in NAFLD/NASH, new drugs and treatment protocols may require the use of anti-inflammatory compounds, such as berberine, in combination with bile acid receptor agonists or antagonists. Emerging new molecular technologies may provide guidance in unraveling the complex physiological pathways driving fatty liver disease and better approaches to prevention and treatment. © 2021 American Physiological Society. Compr Physiol 11:1-12, 2021., (Copyright © 2022 American Physiological Society. All rights reserved.)

Discusses surface color centers as novel hydrogen bond acceptors. Specific interaction between surface OH groups and surface color centers on nanometer-sized MgO particles; Positions of the respective OH stretching bands; Bandwidths' indication that the color center electron as proton acceptor is strongly localized.

This study focused on determining the learning experiences and lessons learned by Senior High School (SHS) STEM students in General Biology 1 in a private sectarian college in Batangas Province, Philippines. These students implemented scientific inquiry through problem-based learning as the main instructional approach in SHS biology pedagogy. This research utilized a descriptive qualitative approach to study STEM students' experiences using axial coding to identify pertinent narratives and themes on scientific inquiry and problem-based learning. Results of the study showed five pertinent narratives or themes on how SHS students conduct critical thinking about biological science in the classroom. The narrative themes are the following: (1) SHS STEM students analyze biological problems and formulate hypothesis through intensive research by reading related articles and critical issue identification; (2) SHS STEM students synthesize details by collaboratively brainstorming or discussing within their group and primarily accessing their prior knowledge to come up with solutions to the biological issue; (3) SHS STEM students classified variables involved in the biological problem by determining the cause-and-effect relationships in the issue; (4) SHS STEM students compare their outputs and criticized experimental designs collaboratively by sharing their varied concepts and ideas to one another; and (5) SHS STEM students make real-life connections because of the problem's perceived importance or application, allowing them to convince others on the validity of their experiments. The findings of this study provided significant information on how SHS STEM students' perception on scientific inquiry through problem-based learning method actually helped them in designing scientific investigations. This study further shed light on various areas of weakness of SHS STEM students, e.g., failure to focus on the scientific merit of questions generated and to systematically collect and analyze data and draw conclusions. [ABSTRACT FROM AUTHOR]

Cognitive training in MCI may stimulate pre-existing neural reserves or recruit neural circuitry as 'compensatory scaffolding' prompting neuroplastic reorganization to meet task demands (Reuter-Lorenz & Park, 2014). However, existing systematic reviews and meta-analytic studies exploring the benefits of cognitive interventions in MCI have been mixed. An updated examination regarding the efficacy of cognitive intervention in MCI is needed given improvements in adherence to MCI diagnostic criteria in subject selection, better defined interventions and strategies applied, increased use of neuropsychological measures pre- and post-intervention, as well as identification of moderator variables which may influence treatment. As such, this meta-analytic review was conducted to examine the efficacy of cognitive intervention in individuals diagnosed with mild cognitive impairment (MCI) versus MCI controls based on performance of neuropsychological outcome measures in randomized controlled trials (RCT). RCT studies published from January 1995 to June 2017 were obtained through source databases of MEDLINE-R, PubMed, Healthstar, Global Health, PSYCH-INFO, and Health and Psychological Instruments using search parameters for MCI diagnostic category (mild cognitive impairment, MCI, pre-Alzheimer's disease, early cognitive decline, early onset Alzheimer's disease, and preclinical Alzheimer's disease) and the intervention or training conducted (intervention, training, stimulation, rehabilitation, or treatment). Other inclusion and exclusion criteria included subject selection based on established MCI criteria, RCT design in an outpatient setting, MCI controls (active or passive), and outcomes based on objective neuropsychological measures. From the 1199 abstracts identified, 26 articles met inclusion criteria for the meta-analyses completed across eleven (11) countries; 92.31% of which have been published within the past 7 years. A series of meta-analyses were performed to examine the effects of cognitive intervention by cognitive domain, type of training, and intervention content (cognitive domain targeted). We found significant, moderate effects for multicomponent training (Hedges' g observed = 0.398; CI [0.164, 0.631]; Z = 3.337; p = 0.001; Q = 55.511; df = 15; p = 0.000; I = 72.978%; τ = 0.146) as well as multidomain-focused strategies (Hedges' g = 0.230; 95% CI [0.108, 0.352]; Z = 3.692; p < 0.001; Q = 12.713; df = 12; p = 0.390; I = 5.612; τ = 0.003). The effects for other interventions explored by cognitive domain, training type, or intervention content were indeterminate due to concerns for heterogeneity, bias, and small cell sizes. In addition, subgroup and meta-regression analyses were conducted with the moderators of MCI category, mode of intervention, training type, intervention content, program duration (total hours), type of control group (active or passive), post-intervention follow-up assessment period, and control for repeat administration. We found significant overall effects for intervention content with memory focused interventions appearing to be more effective than multidomain approaches. There was no evidence of an influence on outcomes for the other covariates examined. Overall, these findings suggest individuals with MCI who received multicomponent training or interventions targeting multiple domains (including lifestyle changes) were apt to display an improvement on outcome measures of cognition post-intervention. As such, multicomponent and multidomain forms of intervention may prompt recruitment of alternate neural processes as well as support primary networks to meet task demands simultaneously. In addition, interventions with memory and multidomain forms of content appear to be particularly helpful, with memory-based approaches possibly being more effective than multidomain methods. Other factors, such as program duration, appear to have less of an influence on intervention outcomes. Given this, although the creation of new primary network paths appears strained in MCI, interventions with memory-based or multidomain forms of content may facilitate partial activation of compensatory scaffolding and neuroplastic reorganization. The positive benefit of memory-based strategies may also reflect transfer effects indicative of compensatory network activation and the multiple-pathways involved in memory processes. Limitations of this review are similar to other meta-analysis in MCI, including a modest number studies, small sample sizes, multiple forms of interventions and types of training applied (some overlapping), and, while greatly improved in our view, a large diversity of instruments used to measure outcome. This is apt to have contributed to the presence of heterogeneity and publication bias precluding a more definitive determination of the outcomes observed. [ABSTRACT FROM AUTHOR]

Purpose: UTROSCTs are rare neoplasms of the uterine corpus. The authors report the clinicopathological characteristics of two cases of UTROSCTs and review the literature on these tumors. Materials and Methods: Medical records of two patients treated for an UTROSCT were analysed. A comprehensive review of literature was also performed. Results: Case 1:A 49-year old patient underwent an abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH-BSO) for a suspected leiomyoma. The uterus contained leiomyomas and a 1.8-cm nodule diagnosed as an UTROSCT. Immunohistochemical analysis showed positivity for sex-cord and smooth muscle markers. Case 2: A 43-year-old patient underwent TAH-BSO for a uterine tumor adherent to the sigmoid serosa and pelvic peritoneum. Debulking surgery allowed complete cytoreduction. The pathologic analysis was compatible with UTROSCT. Cells stained for sex-cord and epithelial markers. Patient received adjuvant chemotherapy with bleomycin, etoposide, and cisplatin. Forty months after surgery, a three-cm UTROSCT lesion in the posterior cul-de-sac was surgically removed. Review of Literature: A review of the literature identified 85 cases of UTROSCTs. Hysterectomy is the gold standard therapy. More conservative surgery is an option for selected patients of childbearing age who wish to maintain their fertility potential. Recurrence or metastases are mainly addressed surgically. Conclusion: Due to the scarcity of published cases, there is little definite knowledge about UTROSCTs. UTROSCTs are of low malignant potential, thus long term follow-up is recommended. [ABSTRACT FROM AUTHOR]

Teachers who organize for educational equity and social justice generally do so through teacher-led professional networks. Community organizations (COs) that seek to support such teacher leaders can face challenges in working with their organic and often horizontally organized networks. This article examines three case studies of COs that developed successful alliances with urban teacher leaders in teacher-led networks and identifies specific strategies COs used to support the teachers. [ABSTRACT FROM PUBLISHER]