Miracle-dz/UniFAR-FTUs huggingface dataset:
The incidence and epidemiology of plasma cell neoplasms.

Plasma cell neoplasia includes monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), and Waldenström's macroglobulinemia (WM). In MGUS, a large, stable clone does not cause symptoms; additional change(s) is/are required to convert this clone into a progressively expanding tumor that becomes symptomatic, as in MM or WM. The prevalence of MGUS (i.e., the number of cases in a defined population at a certain time) is 20 times greater than MM. The incidence (i.e., the number of cases developing in a defined population in a defined period) has not been determined for MGUS. Between 1960 and 1969, the average, annual, age-adjusted (1950 standard) incidence of MM in Malmö, Sweden was 3.4/10(5). The incidence of MM is strongly influenced by the age and race of the population, and the diagnostic services available. MM is a disease of old age; it rarely occurs before the age of 40. The incidence of MM increases rapidly with age, is lowest among the Chinese and Japanese, intermediate among Caucasians in America and Europe, and highest among blacks in the USA. The striking differences in the incidence of MM in different countries appears to be due to racial rather than environmental differences, since the low incidence among the Chinese and Japanese in Asia has migrated with them to the Bay area of California and to Hawaii. The high incidence of MM in USA black males (10.8/10(5)) and females (7.2/10(5)) is more than twice the rate for whites in the same regions. (ABSTRACT TRUNCATED AT 250 WORDS)
Neuropsychology in South Africa: confronting the challenges of specialist practice in a culturally diverse developing country

Abstract Objective: This was an invited paper on the history and current status of neuropsychology in South Africa. Method: Information was gathered from literature searches, personal communication, and the authors’ experiences while occupying relevant professional and academic positions for over 30 years. Results: Since its origins in the 1950s, the development of neuropsychology in South Africa has faced numerous challenges, against a background of extreme sociocultural and socioeconomic disparity in the country that is on-going. The creation of the South African Clinical Neuropsychological Society in the 1980s, a credentialing and training body, gave impetus to the discipline. In the absence of a neuropsychology category within the South African professional framework, university instruction has been ad hoc with vastly different levels of competency depending on the institution involved. The small number of practitioners and/or academics involved in neuropsychology includes mainly masters, and some doctoral level psychologists registered in clinical, counseling or educational categories. A prime emphasis of neuropsychological research has been local norming of psychometric tests to facilitate valid assessment practices in the country. South Africa is on the cusp of achieving a hard-won neuropsychology professional register. It is anticipated that this development will provide impetus to the discipline by promoting training programs, the creation of neuropsychology posts, wider service delivery, and increased research funding. Conclusions: Despite significant challenges in a culturally diverse, developing country, neuropsychology has evolved sufficiently to warrant the creation of a separate category in the professional framework. This development will facilitate training, research, and services in the country.
Regulation of Activity of Transient Receptor Potential Melastatin 8 (TRPM8) Channel by Its Short Isoforms*

Background: The mechanism of regulation of ion channels often involves interaction with their nonfunctional isoforms. Results: Cloned short isoforms of the TRPM8 cold receptor channel negatively regulate its activation mechanisms. Conclusion: By affecting the stability of the TRPM8 C terminus, short isoforms weaken channel gating by cold and decrease its open probability (Po). Significance: This helps to understand the mechanisms of TRPM8 activation. One important mechanism of the regulation of membrane ion channels involves their nonfunctional isoforms generated by alternative splicing. However, knowledge of such isoforms for the members of the transient receptor potential (TRP) superfamily of ion channels remains quite limited. This study focuses on the TRPM8, which functions as a cold receptor in sensory neurons but is also expressed in tissues not exposed to ambient temperatures, as well as in cancer tissues. We report the cloning from prostate cancer cells of new short splice variants of TRPM8, termed short TRPM8α and short TRPM8β. Our results show that both variants are in a closed configuration with the C-terminal tail of the full-length TRPM8 channel, resulting in stabilization of its closed state and thus reducing both its cold sensitivity and activity. Our findings therefore uncover a new mode of regulation of the TRPM8 channel by its splice variants.
Prevalence of Chronic Obstructive Pulmonary Disease according to BTS, ERS, GOLD and ATS Criteria in Relation to Doctor’s Diagnosis, Symptoms, Age, Gender, and Smoking Habits

Background: Guidelines and standards for diagnosis and management of chronic obstructive pulmonary disease (COPD) have been presented by different national and international societies, but the spirometric criteria for COPD differ between guidelines. Objectives: To estimate prevalence of COPD using the guidelines of the British Thoracic Society (BTS), the European Respiratory Society (ERS), the Global Initiative for Chronic Obstructive Lung Disease (GOLD), and the American Thoracic Society (ATS). Further, to evaluate reported airway symptoms, contacts with health care providers, and physician diagnosis of COPD in relation to the respective criteria, and gender differences. Method: In 1992 a postal questionnaire was sent to a random sample of adults aged 20–69 years, 4,851 (85%) out of 5,681 subjects responded. In 1994–1995 a random sample of the responders, 970 subjects, were invited to a structured interview and a lung function test; 666 (69%) participated. Results: The prevalence of COPD was 7.6, 14.0, 14.1, 12.2 and 34.1% according to BTS, ERS, GOLD, clinical ATS (with symptoms or physician diagnosis), and spirometric ATS criteria, respectively. Prevalent COPD was related to age, smoking habits and family history of obstructive airway disease but not to gender. Physician diagnosis of chronic bronchitis or emphysema was only reported by 16.3, 12.2, 11.0, 23.4 and 8.2% of subjects fulfilling the respective criteria, though a majority reported airway symptoms. Conclusion: The main determinants for prevalent COPD were age, smoking habits and spirometric criteria of COPD. Though a majority reported airway symptoms and contact with health care providers due to respiratory complaints, only a minority was diagnosed as having COPD, indicating a large underdiagnosis.
Depressive Symptoms Increase the Likelihood of Cognitive Impairment in Elderly People with Subclinical Alzheimer Pathology

The objective of this study was to investigate whether the presence of depressive symptoms influences the clinical expression of Alzheimer’s pathology. We have analysed the relationships between the severity of Alzheimer’s pathology and cognitive decline in two patient groups defined by the presence or absence of depressive symptoms. The study included 89 subjects who participated in a longitudinal research programme prior to death, underwent post-mortem examination and were found to have only Alzheimer-type pathology in their brains, ranging in severity from the entorhinal to neocortical stages. Our results indicate that depressive symptoms did not influence cognition in the early (entorhinal) stages of Alzheimer’s disease (AD; where cognition was good regardless of whether or not there was evidence for depressive symptoms) or in the late (neocortical) stages (where cognition was poor regardless of whether or not there was evidence for depression). However, in the intermediate (limbic) stages, patients with depressive symptoms had significantly worse cognitive performance (mean CAMCOG of 32) than those who did not (mean CAMCOG of 73). We conclude that depressive symptoms may contribute to the cognitive decline of AD patients in that pathology, that would be otherwise silent, becomes clinically apparent. Therefore, a multiple diagnosis of early AD and depression should be more widely considered in elderly persons presenting with mild cognitive decline and depression. Treating the depressive symptoms would benefit the patient, but the cognitive improvement may not indicate that AD is absent.
Effect of R-(+)-alpha-lipoic acid on experimental diabetic retinopathy.

AIMS/HYPOTHESIS Hyperglycaemia-induced mitochondrial overproduction of reactive oxygen species (ROS) is central to the pathogenesis of endothelial damage in diabetes. R-(+)-alpha-lipoic acid has advantages over classic antioxidants, as it distributes to the mitochondria, is regenerated by glycolytic flux, and has a low redox potential. METHODS To assess the effect of R-(+)-alpha-lipoic acid on experimental diabetic retinopathy, three groups of male Wistar rats were studied: non-diabetic controls, untreated diabetic controls, and diabetic rats treated with 60 mg/kg bodyweight R-(+)-alpha-lipoic acid i.p. for 30 weeks. Quantitative retinal morphometry included acellular occluded capillaries and pericyte numbers. The effects of R-(+)-alpha-lipoic acid on parameters of oxidative and nitrative stress, AGE and its receptor and nuclear factor kappa B (NFkappaB) were assessed by immunoblotting, and NFkappaB activation by electrophoretic mobility shift assay. Angiopoietin-2 and vascular endothelial growth factors were also determined by immunoblotting. RESULTS After 30 weeks of diabetes, the number of acellular capillaries was significantly elevated in diabetic rats (57.1+/-10.6 acellular capillary segments [ac]/mm(2) of retinal area) compared with non-diabetic (19.8+/-5.1 ac/mm(2); p<0.001). Treatment with 60 mg/kg R-(+)-alpha-lipoic acid reduced the numbers by 88% (p<0.001 vs diabetic). Pericyte loss was also significantly inhibited in diabetic rats treated with R-(+)-alpha-lipoic acid (non-diabetic: 1,940+/-137 pericytes/mm(2)capillary area; untreated diabetic: 1,294+/-94 pericytes/mm(2)capillary area vs treated diabetic: 1,656+/-134 pericytes/mm(2); p<0.01). R-(+)-alpha-lipoic acid treatment reduced oxidative stress, normalised NFkappaB activation and angiopoietin-2 expression, and reduced vascular endothelial growth factor in the diabetic retina by 43% (p<0.0001). CONCLUSIONS/INTERPRETATION R-(+)-alpha-lipoic acid prevents microvascular damage through normalised pathways downstream of mitochondrial overproduction of ROS, and preserves pericyte coverage of retinal capillaries, which may provide additional endothelial protection.
The El Tor Biotype of Vibrio cholerae Exhibits a Growth Advantage in the Stationary Phase in Mixed Cultures with the Classical Biotype

ABSTRACT Vibrio cholerae strains of the O1 serogroup that typically cause epidemic cholera can be classified into two biotypes, classical and El Tor. The El Tor biotype emerged in 1961 and subsequently displaced the classical biotype as a cause of cholera throughout the world. In this study we demonstrate that when strains of the El Tor and classical biotypes were cocultured in standard LB medium, the El Tor strains clearly had a competitive growth advantage over the classical biotype starting from the late stationary phase and could eventually take over the population. The classical biotype produces extracellular protease(s) in the stationary phase, and the amounts of amino acids and small peptides in the late stationary and death phase culture filtrates of the classical biotype were higher than those in the corresponding culture filtrates of the El Tor biotype. The El Tor biotype cells could utilize the amino acids more efficiently than the classical biotype under the alkaline pH of the stationary phase cultures but not in medium buffered to neutral pH. The growth advantage of the El Tor biotype was also observed in vivo using the ligated rabbit ileal loop and infant mouse animal models.
Multiple domains of the large fibroblast proteoglycan, versican.

The primary structure of a large chondroitin sulfate proteoglycan expressed by human fibroblasts has been determined. Overlapping cDNA clones code for the entire 2389 amino acid long core protein and the 20‐residue signal peptide. The sequence predicts a potential hyaluronic acid‐binding domain in the amino‐terminal portion. This domain contains sequences virtually identical to partial peptide sequences from a glial hyaluronate‐binding protein. Putative glycosaminoglycan attachment sites are located in the middle of the protein. The carboxy‐terminal portion includes two epidermal growth factor (EGF)‐like repeats, a lectin‐like sequence and a complement regulatory protein‐like domain. The same set of binding elements has also been identified in a new class of cell adhesion molecules. Amino‐ and carboxy‐terminal portions of the fibroblast core protein are closely related to the core protein of a large chondroitin sulfate proteoglycan of chondrosarcoma cells. However, the glycosaminoglycan attachment regions in the middle of the core proteins are different and only the fibroblast core protein contains EGF‐like repeats. Based on the similarities of its domains with various binding elements of other proteins, we suggest that the large fibroblast proteoglycan, herein referred to as versican, may function in cell recognition, possibly by connecting extracellular matrix components and cell surface glycoproteins.
Kinetic mechanism and some properties of glucose-6- phosphate dehydrogenase from sheep brain cortex

Objective: Glucose-6-phosphate dehydrogenase is an important key enzyme which catalyzes the first oxidative step of the pentose phosphate pathway. The objectives of this study are to determine some properties and kinetic mechanism of glucose-6-phosphate dehydrogenase. Method: In this study we used the enzyme that was purified from sheep brain cortex. The kinetic analysis and other studies were performed within three days after the purification to prevent any loss of enzyme activity. Results: The subunit molecular weight was determined as 61.2 kDa by SDS-PAGE and 64.5 kDa by Sephadex G-200 gel filtration chromatography. The activation energy (Ea) of the reaction was calculated from the Arrhenius plot as 6.689 kcal/mol. We have calculated the temperature coefficient as 1.913 from the integrated form of the Arrhenius equation (for the temperatures between 30 - 40 oC). Optimum pH of the enzyme was determined as 8. Kinetic constants estimated by a nonlinear curve-fitting program are as follows: Vm= 2.182 ± 0.064 mmol/min/mg enzyme; Km NADP+ = 0.064 ± 0.001 mM; Km G6P = 0.0729 ± 0.006 mM; Ki G6P = 0.074 ± 0.003 mM; Ki NADP+ = 0.056 ± 0.001mM. Conclusion: Sheep brain cortex glucose-6-phosphate dehydrogenase exhibits classical Michaelis-Menten kinetics. Product inhibition studies were undertaken to distinguish the type of the mechanism. We have found that G6PD enzyme obeys 'Theorell-Chance' mechanism. The kinetic behavior, molecular weight, optimum temperature and pH of the enzyme were in accordance with our previous studies.
Genetic variation in the autophagy gene ULK1 and risk of Crohn's disease

Background: The autophagy pathway has been linked with Crohn's disease (CD) through association of the ATG16L1 and IRGM genes with susceptibility for CD, and also to the Nod2 pathway, involved in CD. Our aim was to investigate polymorphisms in selected autophagy genes for their association with susceptibility to CD. Methods: We prioritized all known human homologs of yeast autophagy (Atg) genes according to their location in a known inflammatory bowel disease (IBD) locus or in a genomic region detected in a genome‐wide association study (GWAS) or GWAS‐meta‐analysis. A total of 70 haplotype tagging single nucleotide polymorphisms (tSNPs) in 12 genes were genotyped in a cohort of CD patients (n = 947) and controls (n = 548). Transmission disequilibrium testing (TDT) was performed in an independent cohort of 335 parent‐child CD‐trios. Results: The frequency of the T‐allele of tSNP rs12303764 in ULK1 was significantly higher in CD (64%) versus controls (57%, corrected P‐value 0.002). TDT demonstrated overtransmission of this allele to affected offspring (P = 0.02). Model‐based multifactor dimensionality reduction (MB‐MDR) interaction analysis confirmed a strong main effect for rs12303764. No interaction was found between ULK1 and CARD15, or between ULK1 genotypes and CD phenotypes. Conclusions: We report a genetic association with a tSNP in ULK1, an interesting candidate gene for IBD, given the role of ULK1 in autophagy initiation, and the interaction between Nod2 and autophagy pathways. To further clarify the role of ULK1 in CD, an in‐depth investigation of the variation in the region and possible role for copy number variation in this region should be evaluated. (Inflamm Bowel Dis 2011)
Donor splice‐site mutation in CUL4B is likely cause of X‐linked intellectual disability

X‐linked intellectual disability is the most common form of cognitive disability in males. Syndromic intellectual disability encompasses cognitive deficits with other medical and behavioral manifestations. Recently, a large family with a novel form of syndromic X‐linked intellectual disability was characterized. Eight of 24 members of the family are male and had cognitive dysfunction, short stature, aphasia, skeletal abnormalities, and minor anomalies. To identify the causative gene(s), we performed exome sequencing in three affected boys, both parents, and an unaffected sister. We identified a haplotype consisting of eight variants located in cis within the linkage region that segregated with affected members in the family. Of these variants, two were novel. The first was at the splice‐donor site of intron 7 (c.974+1G>T) in the cullin‐RING ubiquitin ligase (E3) gene, CUL4B. This variant is predicted to result in failure to splice and remove intron 7 from the primary transcript. The second variant mapped to the 3′‐UTR region of the KAISO gene (c.1127T>G). Sanger sequencing validated the variants in these relatives as well as in three affected males and five carriers. The KAISO gene variant was predicted to create a binding site for the microRNAs miR‐4999 and miR‐4774; however, luciferase expression assays failed to validate increased targeting of these miRNAs to the variant 3′‐UTR. This SNP may affect 3′‐UTR structure leading to decreased mRNA stability. Our results suggest that the intellectual disability phenotype in this family is caused by aberrant splicing and removal of intron 7 from CUL4B gene primary transcript. © 2014 Wiley Periodicals, Inc.
Actin‐based motility of pathogens: the Arp2/3 complex is a central player

Bacterial actin‐based motility has provided cell biologists with tools that led to the recent discovery that, in many forms of actin‐based motilities, a key player is a protein complex named the Arp2/3 complex. The Arp2/3 complex is evolutionally conserved and made up of seven polypeptides involved in both actin filament nucleation and organization. Interestingly, this complex is inactive by itself and recent work has highlighted the fact that its activation is achieved differently in the different types of actin‐based motilities, including the well‐known examples of Listeria and Shigella motilities. Proteins of the WASP family and small G‐proteins are involved in most cases. It is interesting that bacteria bypass or mimic some of the events occurring in eukaryotic systems. The Shigella protein IcsA recruits N‐WASP and activates it in a Cdc42‐like fashion. This activation leads to Arp2/3 complex recruitment, activation of the complex and ultimately actin polymerization and movement. The Listeria ActA protein activates Arp2/3 directly and, thus, seems to mimic proteins of the WASP family. A breakthrough in the field is the recent reconstitution of the actin‐based motilities of Listeria and N‐WASP‐coated E. coli (IcsA) using a restricted number of purified cellular proteins including F‐actin, the Arp2/3 complex, actin depolymerizing factor (ADF or cofilin) and capping protein. The movement was more effective upon addition of profilin, α‐actinin and VASP (for Listeria). Bacterial actin‐based motility is now one of the best‐documented examples of the exploitation of mammalian cell machineries by bacterial pathogens.
Lead-free Perovskite Materials (NH4 )3 Sb2 Ix Br9-x.

A family of perovskite light absorbers (NH4 )3 Sb2 Ix Br9-x (0≤x≤9) was prepared. These materials show good solubility in ethanol, a low-cost, hypotoxic, and environmentally friendly solvent. The light absorption of (NH4 )3 Sb2 Ix Br9-x films can be tuned by adjusting I and Br content. The absorption onset for (NH4 )3 Sb2 Ix Br9-x films changes from 558 nm to 453 nm as x changes from 9 to 0. (NH4 )3 Sb2 I9 single crystals were prepared, exhibiting a hole mobility of 4.8 cm2 V-1 s-1 and an electron mobility of 12.3 cm2 V-1 s-1 . (NH4 )3 Sb2 I9 solar cells gave an open-circuit voltage of 1.03 V and a power conversion efficiency of 0.51 %.
Evaluation of the impact of the baby-friendly hospital initiative on rates of breastfeeding.

The Baby-Friendly Hospital Initiative (BFHI) is based on the Ten Steps to Successful Breast-Feeding, a program which summarize the practices that maternity wards need to adopt to support breastfeeding.1 There are more than 16 000 Baby-Friendly Hospitals throughout the world, and of these, more than 200 are located in Brazil. Despite the abundance of studies evaluating each of the 10 steps or a combination of them, information on the impact of BFHI on the duration of breastfeeding is limited. Recently, a large randomized controlled trial including 31 hospitals in Belarus showed that an intervention based on BFHI principles increased breastfeeding rates, especially exclusive breastfeeding.2 The present study reproduced these results using a less complex study design.
Chemical composition of the essential oil and botanical study of the flowers of Mentha suaveolens

Abstract Context: Herbal medicines play a paramount role in the treatment of wide range of diseases, so there is a growing need for their quality control and standardization. Traditionally, histological and morphological inspections have been the usual methods to authenticate herbs intended for medicinal applications. Mentha suaveolens Ehrh. (Lamiaceae) is native to Africa Temperate Asia and Europe and it's cultivated in Egypt. Objective: The macro- and micromorphology of the flowers of M. suaveolens Ehrh. cultivated in Egypt were studied to find the diagnostic characters of this species. In addition, the chemical composition of the essential oil of the flowers was also studied to define the chemotype of the plant. Materials and methods: Photographs of macro- and micromorphology were taken using Casio and Leica DFC500 digital cameras, respectively. In addition, the essential oil was prepared by hydrodistillation followed by gas chromatographic/mass spectrometric (GC/MS) analysis for identification of its components. Results: The macro- and micromorphological characteristics of M. suaveolens were determined. The yield of the essential oil obtained by hydrodistillation from M. suaveolens flowers was 1.7% calculated on dry weight basis. GC/MS analysis of the oil resulted in identification of 29 components, which amounted to 99.77% of the total oil composition. The major component was carvone (50.59%) followed by limonene (31.25%). Discussion and conclusion: The results obtained herein revealed for the macro, micromorphological and chemical composition characteristics of the flowers. The results of GC/MS analysis of the essential oil supported that M. suaveolens cultivated in Egypt could be categorized as carvone-rich chemotype since this compound pertained its high relative percentile.