Geoengineering characterization of the rock masses of northern face of Jabal Sabir, Taiz city, Yemen

This paper is aimed at thedescription and the geotechnical characterization of the Tertiary granitic rock masses of the northern face of Sabir Mountain, Taiz city, Yemen, for the first time. For accomplishing this task, direct and indirect approaches are adopted. The direct approach is represented by field and laboratory investigations. Field investigations include discontinuity (joints) measurements/evaluation, applied Rock Mass Rating (RMR) system and Geological Strength Index (GSI) system, in addition to field tests, while laboratory investigations encompass physico-mechanical tests carried out on granitic rock materials. Indirect approach for the estimation of shear strength parameters (c, Ø), compressive strength (σcm), tensile strength (σtm) and deformation modulus (Erm) of these rock masses was made by applying the generalized Hoek–Brown failure criterion using geotechnical Roc-Lab software. The laboratory results indicate that the Tertiary granitic rock masses show wide range of variations in their physico-mechanical characteristics owing to degree of weathering /alteration and microfractures. The intact samples of Sabir granitic (Tg) rocks show "Moderate"to "High"density, "Low"to "Medium"porosity, "Good"to "Marginal"water absorption capacity and "Weak"to "Very Strong"strength. Stereographically, three main sets of discontinuities (joints) are identified at each station; however, the fourth joint set occurs, in addition to random joint sets. The discontinuities (joints) trend predominately in NE-SW and NW-SE directions in conformity with the regional structures or faults. According to Jv j/m³values, the degree of jointing of these rock masses are varied from "Moderate"to "High"jointing. These rocks are categorized as "Fair"to "Excellent"quality, "Fair"to "Good/Very Good"quality and "Poor"to "Very Good"quality classes according to RQD, RMRb89and GSI respectively. Values ofthe shear strength parameters (c and Ø) and the other rock mass parameters (σtm, σc, σcmand Erm) show variations depending on the rock mass quality and properties of intact rock. However, in general the values of the rock mass parameters are found to increase with increase in the quality of rock mass and intact rock properties

Polymorphism of alpha-1-antitrypsin in hematological malignancies

Alpha-1-antitrypsin (AAT) or serine protease inhibitor A1 (SERPINA1) is an important serine protease inhibitor in humans. The main physiological role of AAT is to inhibit neutrophil elastase (NE) released from triggered neutrophils, with an additional lesser role in the defense against damage inflicted by other serine proteases, such as cathepsin G and proteinase 3. Although there is a reported association between AAT polymorphism and different types of cancer, this association with hematological malignancies (HM) is, as yet, unknown. We identified AAT phenotypes by isoelectric focusing (in the pH 4.2-4.9 range) in 151 serum samples from patients with HM (Hodgkins lymphomas, non-Hodgkins lymphomas and malignant monoclonal gammopathies). Healthy blood-donors constituted the control group (n = 272). The evaluated population of patients as well as the control group, were at Hardy-Weinberg equilibrium for the AAT gene (χ2 = 4.42, d.f.11, p = 0.96 and χ2 = 4.71, d.f.11, p = 0.97, respectively). There was no difference in the frequency of deficient AAT alleles (Pi Z and Pi S) between patients and control. However, we found a significantly higher frequency of PiM1M1 homozygote and PiM1 allele in HM patients than in control (for phenotype: f = 0.5166 and 0.4118 respectively, p = 0.037; for allele: f = 0.7020 and 0.6360 respectively, p = 0.05). In addition, PiM homozygotes in HM-patients were more numerous than in controls (59% and 48%, respectively, p = 0.044). PiM1 alleles and PiM1 homozygotes are both associated with hematological malignancies, although this is considered a functionally normal AAT variant

Mitochondrial and endoplasmic reticulum stress pathways cooperate in zearalenone-induced apoptosis of human leukemic cells

<p>Abstract</p> <p>Background</p> <p>Zearalenone (ZEA) is a phytoestrogen from <it>Fusarium </it>species. The aims of the study was to identify mode of human leukemic cell death induced by ZEA and the mechanisms involved.</p> <p>Methods</p> <p>Cell cytotoxicity of ZEA on human leukemic HL-60, U937 and peripheral blood mononuclear cells (PBMCs) was performed by using 3-(4,5-dimethyl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Reactive oxygen species production, cell cycle analysis and mitochondrial transmembrane potential reduction was determined by employing 2',7'-dichlorofluorescein diacetate, propidium iodide and 3,3'-dihexyloxacarbocyanine iodide and flow cytometry, respectively. Caspase-3 and -8 activities were detected by using fluorogenic Asp-Glu-Val-Asp-7-amino-4-methylcoumarin (DEVD-AMC) and Ile-Glu-Thr-Asp-7-amino-4-methylcoumarin (IETD-AMC) substrates, respectively. Protein expression of cytochrome c, Bax, Bcl-2 and Bcl-xL was performed by Western blot. The expression of proteins was assessed by two-dimensional polyacrylamide gel-electrophoresis (PAGE) coupled with LC-MS2 analysis and real-time reverse transcription polymerase chain reaction (RT-PCR) approach.</p> <p>Results</p> <p>ZEA was cytotoxic to U937 > HL-60 > PBMCs and caused subdiploid peaks and G1 arrest in both cell lines. Apoptosis of human leukemic HL-60 and U937 cell apoptosis induced by ZEA was via an activation of mitochondrial release of cytochrome c through mitochondrial transmembrane potential reduction, activation of caspase-3 and -8, production of reactive oxygen species and induction of endoplasmic reticulum stress. Bax was up regulated in a time-dependent manner and there was down regulation of Bcl-xL expression. Two-dimensional PAGE coupled with LC-MS2 analysis showed that ZEA treatment of HL-60 cells produced differences in the levels of 22 membrane proteins such as apoptosis inducing factor and the ER stress proteins including endoplasmic reticulum protein 29 (ERp29), 78 kDa glucose-regulated protein, heat shock protein 90 and calreticulin, whereas only <it>ERp29 </it>mRNA transcript increased.</p> <p>Conclusion</p> <p>ZEA induced human leukemic cell apoptosis via endoplasmic stress and mitochondrial pathway.</p

Global, regional, and national burden of other musculoskeletal disorders, 1990–2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021

Background Musculoskeletal disorders include more than 150 different conditions affecting joints, muscles, bones, ligaments, tendons, and the spine. To capture all health loss from death and disability due to musculoskeletal disorders, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) includes a residual musculoskeletal category for conditions other than osteoarthritis, rheumatoid arthritis, gout, low back pain, and neck pain. This category is called other musculoskeletal disorders and includes, for example, systemic lupus erythematosus and spondylopathies. We provide updated estimates of the prevalence, mortality, and disability attributable to other musculoskeletal disorders and forecasted prevalence to 2050. Methods Prevalence of other musculoskeletal disorders was estimated in 204 countries and territories from 1990 to 2020 using data from 68 sources across 23 countries from which subtraction of cases of rheumatoid arthritis, osteoarthritis, low back pain, neck pain, and gout from the total number of cases of musculoskeletal disorders was possible. Data were analysed with Bayesian meta-regression models to estimate prevalence by year, age, sex, and location. Years lived with disability (YLDs) were estimated from prevalence and disability weights. Mortality attributed to other musculoskeletal disorders was estimated using vital registration data. Prevalence was forecast to 2050 by regressing prevalence estimates from 1990 to 2020 with Socio-demographic Index as a predictor, then multiplying by population forecasts. Findings Globally, 494 million (95% uncertainty interval 431–564) people had other musculoskeletal disorders in 2020, an increase of 123·4% (116·9–129·3) in total cases from 221 million (192–253) in 1990. Cases of other musculoskeletal disorders are projected to increase by 115% (107–124) from 2020 to 2050, to an estimated 1060 million (95% UI 964–1170) prevalent cases in 2050; most regions were projected to have at least a 50% increase in cases between 2020 and 2050. The global age-standardised prevalence of other musculoskeletal disorders was 47·4% (44·9–49·4) higher in females than in males and increased with age to a peak at 65–69 years in male and female sexes. In 2020, other musculoskeletal disorders was the sixth ranked cause of YLDs globally (42·7 million [29·4–60·0]) and was associated with 83 100 deaths (73 600–91 600). Interpretation Other musculoskeletal disorders were responsible for a large number of global YLDs in 2020. Until individual conditions and risk factors are more explicitly quantified, policy responses to this burden remain a challenge. Temporal trends and geographical differences in estimates of non-fatal disease burden should not be overinterpreted as they are based on sparse, low-quality data.publishedVersio

Global, regional, and national burden of rheumatoid arthritis, 1990–2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021

Background Rheumatoid arthritis is a chronic autoimmune inflammatory disease associated with disability and premature death. Up-to-date estimates of the burden of rheumatoid arthritis are required for health-care planning, resource allocation, and prevention. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, we provide updated estimates of the prevalence of rheumatoid arthritis and its associated deaths and disability-adjusted life-years (DALYs) by age, sex, year, and location, with forecasted prevalence to 2050. Methods Rheumatoid arthritis prevalence was estimated in 204 countries and territories from 1990 to 2020 using Bayesian meta-regression models and data from population-based studies and medical claims data (98 prevalence and 25 incidence studies). Mortality was estimated from vital registration data with the Cause of Death Ensemble model (CODEm). Years of life lost (YLL) were calculated with use of standard GBD lifetables, and years lived with disability (YLDs) were estimated from prevalence, a meta-analysed distribution of rheumatoid arthritis severity, and disability weights. DALYs were calculated by summing YLLs and YLDs. Smoking was the only risk factor analysed. Rheumatoid arthritis prevalence was forecast to 2050 by logistic regression with Socio-Demographic Index as a predictor, then multiplying by projected population estimates. Findings In 2020, an estimated 17·6 million (95% uncertainty interval 15·8–20·3) people had rheumatoid arthritis worldwide. The age-standardised global prevalence rate was 208·8 cases (186·8–241·1) per 100 000 population, representing a 14·1% (12·7–15·4) increase since 1990. Prevalence was higher in females (age-standardised female-to-male prevalence ratio 2·45 [2·40–2·47]). The age-standardised death rate was 0·47 (0·41–0·54) per 100 000 population (38 300 global deaths [33 500–44 000]), a 23·8% (17·5–29·3) decrease from 1990 to 2020. The 2020 DALY count was 3 060 000 (2 320 000–3 860 000), with an age-standardised DALY rate of 36·4 (27·6–45·9) per 100 000 population. YLDs accounted for 76·4% (68·3–81·0) of DALYs. Smoking risk attribution for rheumatoid arthritis DALYs was 7·1% (3·6–10·3). We forecast that 31·7 million (25·8–39·0) individuals will be living with rheumatoid arthritis worldwide by 2050. Interpretation Rheumatoid arthritis mortality has decreased globally over the past three decades. Global age-standardised prevalence rate and YLDs have increased over the same period, and the number of cases is projected to continue to increase to the year 2050. Improved access to early diagnosis and treatment of rheumatoid arthritis globally is required to reduce the future burden of the disease.publishedVersio

Toksikološka svojstva citrinina

Citrinin (CTN) is a nephrotoxic mycotoxin produced by several fungal strains belonging to the genera Penicillium, Aspergillus, and Monascus. It contaminates various commodities of plant origin, cereals in particular, and is usually found together with another nephrotoxic mycotoxin, ochratoxin A (OTA). These two mycotoxins are believed to be involved in the aetiology of endemic nephropathy. In addition to nephrotoxicity, CTN is also embryocidal and fetotoxic. The genotoxic properties of CTN have been demonstrated with the micronuleus test (MN), but not with single-cell gel electrophoresis. The mechanism of CTN toxicity is not fully understood, especially not whether CTN toxicity and genotoxicity are the consequence of oxidative stress or of increased permeability of mitochondrial membranes. CTN requires complex cellular biotransformation to exert mutagenicity. Compared with other mycotoxins, CTN contamination of food and feed is rather scarce. However, it is reasonable to believe that humans are much more frequently exposed to CTN than generally accepted, because it is produced by the same moulds as OTA, which is a common contaminant of human food all over the world. At present, there are no specifi c regulations either in Croatia or in the European Union concerning CTN in any kind of commodity.Citrinin (CTN) nefrotoksičan je mikotoksin koji proizvode različiti sojevi plijesni iz rodova Penicillium, Aspergillus i Monascus. CTN se može naći u različitim namirnicama biljnog podrijetla, osobito u žitaricama i obično se nalazi zajedno s drugim nefrotoksičnim mikotoksinom, okratoksinom A (OTA). Pretpostavlja se da je izloženost ovim mikotoksinima povezana s nastankom endemske nefropatije. Osim što je nefrotoksičan, CTN je još i embricidan i fetotoksičan. Na genotoksičnost citrinina upućuje pozitivan mikronukleusni test na različitim vrstama staničnih kultura, iako je kometski test negativan. Mutagenost CTN-a očituje se na različitim vrstama stanica samo ako se pridodaju stanični aktivatori kao npr. S9-mix. Mehanizam toksičnosti CTN-a nije potpuno razjašnjen pa još uvijek traje znanstvena rasprava je li njegova toksičnost i genotoksičnost posljedica oksidacijskog stresa ili povećane permeabilnosti mitohondrijskih membrana. U dostupnoj literaturi podaci o kontaminiranosti hrane i krmiva ovim mikotoksinom mnogo su rjeđi od onih za druge mikotoksine. Može se pretpostaviti da su ljudi često izloženi ovom mikotoksinu zato što ga proizvode iste plijesni koje proizvode i OTA, a one kontaminiraju hranu po cijelom svijetu. U Hrvatskoj i u zemljama Europske Unije ne postoje zakonske odredbe o dopuštenim granicama CTN-a u bilo kojoj vrsti hrane

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Geoengineering characterization of the rock masses of northern face of Jabal Sabir, Taiz city, Yemen

This paper is aimed at thedescription and the geotechnical characterization of the Tertiary granitic rock masses of the northern face of Sabir Mountain, Taiz city, Yemen, for the first time. For accomplishing this task, direct and indirect approaches are adopted. The direct approach is represented by field and laboratory investigations. Field investigations include discontinuity (joints) measurements/evaluation, applied Rock Mass Rating (RMR) system and Geological Strength Index (GSI) system, in addition to field tests, while laboratory investigations encompass physico-mechanical tests carried out on granitic rock materials. Indirect approach for the estimation of shear strength parameters (c, Ø), compressive strength (σcm), tensile strength (σtm) and deformation modulus (Erm) of these rock masses was made by applying the generalized Hoek–Brown failure criterion using geotechnical Roc-Lab software. The laboratory results indicate that the Tertiary granitic rock masses show wide range of variations in their physico-mechanical characteristics owing to degree of weathering /alteration and microfractures. The intact samples of Sabir granitic (Tg) rocks show "Moderate"to "High"density, "Low"to "Medium"porosity, "Good"to "Marginal"water absorption capacity and "Weak"to "Very Strong"strength. Stereographically, three main sets of discontinuities (joints) are identified at each station; however, the fourth joint set occurs, in addition to random joint sets. The discontinuities (joints) trend predominately in NE-SW and NW-SE directions in conformity with the regional structures or faults. According to Jv j/m³values, the degree of jointing of these rock masses are varied from "Moderate"to "High"jointing. These rocks are categorized as "Fair"to "Excellent"quality, "Fair"to "Good/Very Good"quality and "Poor"to "Very Good"quality classes according to RQD, RMRb89and GSI respectively. Values ofthe shear strength parameters (c and Ø) and the other rock mass parameters (σtm, σc, σcmand Erm) show variations depending on the rock mass quality and properties of intact rock. However, in general the values of the rock mass parameters are found to increase with increase in the quality of rock mass and intact rock properties