Clinical significance of extrapulmonary tuberculosis in the differential diagnosis of fever of unknown

Tuberkuloza predstavlja infekciju humanim sojem mikobakterije Mycobacterium tuberculosis uz pojavu karakteristiĉnog imunološkog odgovora organizma. Najĉešća forma bolesti je plućna. Po procenama Svetske Zdravstvene Organizacije (SZO) vanplućna tuberkuloza (VPTB) ĉini oko 20-25% formi bolesti. Zbog uglavnom atipiĉne kliniĉke slike (izuzimajući tuberkulozni meningitis), produţenog toka u kome su uz progresivno pogoršanje opšteg stanja, prisutni još samo povišena temperatura i ĉesto pozitivan zapaljenski sindrom, najveći broj ovih bolesnika se razmatra u toku diferencijalne dijagnoze nejasnog febrilnog stanja (NFS). Poseban problem predstavlja teţa dijagnostika VPTB i potreba za ĉešćim korišćenjem invazivne dijagnostike. U periodu do pojave virusa humane imunodeficijencije (HIV) incidenca tuberkuloze u svetu je bila u opadanju, ali se od osamdesetih godina dvadesetog veka tuberkuloza ponovo nameće kao bolest od rastućeg interesa. Procenjuje se da je u svetu oko dve milijarde ljudi inficiranih bacilom M. tuberculosis od kojih je oko 8 miliona godišnje razvije aktivnu tuberkulozu, a oko 2 miliona umre. Incidenca oboljevanja od tuberkuloze i VPTB je u porastu svugde u svetu i u HIV negativnoj populaciji. U takvim okolnostima raste i znaĉaj informisanosti lekara dijagnostiĉara, da se u toku dijagnostiĉkog postupka febrilnog stanja mora razmatrati i tuberkulozna infekcija, kako pluća, tako i vanplućna. Tuberkuloza moţe zahvatiti bilo koji organ u organizmu, s’tim da je plućna lokalizacija najĉešća. Terminom VPTB se oznaĉava izolovana pojava tuberkuloze na bilo kom mestu u organizmu van pluća. Ako je uz vanplućnu lokalizaciju prisutna i zahvaćenost pluća takvi se pacijenti kategorizuju pod dijagnozom plućne tuberkuloze. Varijeteti kliniĉke slike VPTB su mnogobrojni što oteţava dijagnostiku. Uz retke lokalizacije koje daju karakteristiĉne simptome i znake (meningitis) ili bar mogu uputiti u pravcu dijagnoze (tuberkulozni limfadenitis), većina drugih, posebno dubokih lokalizacija se manifestuje samo povišenom temperaturom. Zbog ovakvih teškoća u dijagnostici, proporcionalno je veća zastupljenost VPTB u ukupnom broju otkrivenih bolesnika sa tuberkulozom u tercijarnim ustanovama, nego u primarnoj zdravstvenoj zaštiti...Tuberculosis is an infection with human mycobacteria strain of Mycobacterium tuberculosis, with the occurrence of the characteristic immune response of the organism. The most common form is lung disease. According to estimates by the World Health Organization (WHO), extrapulmonary tuberculosis (EPTB) accounts for 20-25% of the tuberculosis. Mainly due to atypical clinical features (except for tuberculous meningitis), the prolong course of the illness with progressive deterioration of general condition, present only with fever and often positive inflammatory syndrome, most of theses patients are considered in the differential diagnosis of fever of unknown origin (FUO). A particular problem is a difficult diagnosis of EPTB and the need for more frequent use of invasive diagnostic. Until the appearance of human immunodeficiency virus (HIV) incidence of tuberculosis in the world was in decline, but since the eighties of the twentieth century, tuberculosis re-imposed as a disease of growing interest. It is estimated that the world's two billion people infected with an M. tuberculosis, of which about 8 million develop active TB annually, and about 2 million die. The incidence of tuberculosis and EPTB is increasing everywhere in the world and in the HIV negative population too. In such circumstances, medical doctors must have growing awareness of the importance of tuberculosis infection, both lung and extrapulmonary during the diagnostic procedure in febrile conditions. Tuberculosis can affect any organ in the body; however, the most frequent localization is pulmonary. The term EPTB means an isolated occurrence of tuberculosis anywhere in the body outside the lungs. If present with extrapulmonary localization and involvement of the lungs such patients are categorized under the diagnosis of pulmonary tuberculosis. Varieties of clinical presentations of EPTB are numerous which makes diagnosis difficult. With rare localization which give the characteristic signs and symptoms (meningitis), or at least can make towards the diagnosis (tuberculous lymphadenitis), most of the others, especially the deep localization is only manifested with fever. Because of these difficulties in diagnosis, the greater proportion EPTB was detected in tertiary institutions, instead in primary care. The most common localization of EPTB is tuberculosis of the lymph nodes, genitourinary tuberculosis, abdominal tuberculosis, pleural tuberculosis, tuberculous pericarditis, neurotuberculosis, tuberculosis of bones and joints. Other forms of EPTB occur less frequently..

3-Anilino-1-ferrocenylpropan-1-one

In the title ferrocene derivative, [Fe(C5H5)(C14H14NO)], the dihedral angle between the mean planes of the phenyl ring and the substituted cyclo­penta­dienyl ring is 84.4 (1)°. The mol­ecules are connected into centrosymmetric dimers via N—H⋯O hydrogen bonds. In addition, C—H⋯O and C—H⋯N contacts stabilize the crystal packing

1-Ferrocenyl-3-(4-methyl­anilino)propan-1-one

In the title ferrocene derivative, [Fe(C5H5)(C15H16NO)], the dihedral angle between the best planes of the benzene and the substituted cyclo­penta­dienyl ring is 83.4 (1)°. The presence of a methyl substituent in the para position of the aniline group does not alter the crystal packing compared to that of 3-anilino-1-ferrocenylpropan-1-one [Leka et al. (2012 ▶). Acta Cryst. E68, m229]. The molecules are connected into centro­symmetric dimers via N—H⋯O hydrogen bonds. In addition, C—H⋯O and C—H⋯N contacts stabilize the crystal packing

Fundamentalni aspekti procesa elektrohemijskog taloženja olova - nukleacija i rast

In this comprehensive study, the processes of nucleation and growth of lead from electrolytes of various kind and compositions have been analyzed. The processes of Pb nucleation were examined by the analysis of potentiostatic current transients, while the growth process was examined by the scanning electron microscopic (SEM) analysis of the obtained deposits. It was found that nucleation of lead follows Scharifker and Hills (SH) model based on the 3-D instantaneous nucleation with the diffusion controlled growth. Morphologies of lead particles starting from granules produced at the low overpotentials from the dilute electrolytes to very branchy dendrites at the higher ones were formed by the electrodeposition processes. The obtained surface morphologies were correlated with the corresponding polarization characteristics. It was found that regular hexagonal particles are formed by electrodeposition in the ohmic control, while irregular crystals denoted as precursors of dendrites and dendrites of various types (the needle-like, the primary (P) and the secondary (S) dendrites) were formed in the mixed ohmicdiffusion and diffusion controlled electrodeposition. The needle-like and primary (P) dendrites were primarily formed from the basic (nitrate), while the secondary (S) and the tertiary (T) dendrites were formed from the complex (acetate and hydroxide) electrolytes.U ovoj sveobuhvatnoj studiji su analizirani procesi nukleacije i rasta olova iz elektrolita različite vrste i sastava. Procesi nukleacije olova su ispitani analizom potenciostatskih strujnih prelaza, dok procesi rasta su ispitani analizom olovnih taloga tehnikom skenirajuće elektronske mikroskopije (SEM). Nađeno je da nukleacija olova sledi Šarifkerov i Hilsov (SH) model koji se zasniva na 3-D trenutnoj nukleaciji praćenoj difuziono kontrolisanim rastom. Procesima elektrohemijskog taloženja su bile dobijene različite morfologije olovnih čestica, počev od granula dobijenih na malim prenapetostima iz razblaženih elektrolita do veoma razgranatih dendrita na višim prenapetostima. Dobijene morfologije su bile korelisane sa odgovarajućim polarizacionim karakteristikama. Nađeno je da su regularne heksagonalne čestice formirane taloženjem u omskoj kontroli, dok nepravilni kristali označeni kao prekursori dendrita i dendriti različitog oblika (igličasti, primarni (P) i sekundarni (S) dendriti) su bili formirani u mešovito omsko-difuziono i difuziono kontrolisanom taloženju. Igličasti i primarni (P) dendriti su prvenstveno formirani iz osnovnog (nitratnog), dok sekundarni (S) i tercijarni (T) dendriti su formirani iz kompleksnih (acetatnog i hidroksilnog) elektrolita

ELECTROCHEMICAL GENERATION OF A CATALYST FOR MICHAEL ADDITION OF DICARBONYL COMPOUNDS AND CYANIDE ANION TO ACRYLOYLFERROCENE

Michael addition of diethyl malonate, ethyl acetoacetate, acetylacetone, and cyanide anion to acryloylferrocene promoted by a catalyst in situ generated from a sacrificial zirconium anode is described. Most of the obtained compounds were identified by comparison of their spectral and physical data with those published elsewhere, whereas the only newly synthesized compound - diethyl 2,2-bis(3-ferrocenyl-3-oxopropyl)malonate - was completely characterized by spectral (IR, 1H- and 13C-NMR), physical and crystallographic (single-crystal X-ray)  data. ELEKTROHEMIJSKO GENERISANJE KATALIZATORA ZA MAJKLOVU ADICIJU DIKARBONILNIH JEDINJENJA I CIJANIDA NA AKRILOILFEROCENOpisana je Majklova adicija dietil-malonata, etil-acetoacetata, acetilacetona i cijanidnog anjona na akriloilferocen pomoću katalizatora generisanog in situ sa rastvorne anode od cirkonijuma. Većina dobijenih jedinjenja je identifikovana poređenjem njihovih fizičkih i spektroskopskih podataka sa literaturnim, a jedino novo jedinjenje je potpuno opisano spektroskopskim (IR, 1H- i 13C-NMR) i fizičkim podacima, kao i podacima iz kristalografske analize X-zracima. HIGHLIGHTSMichael addition of diethyl malonate, ethyl acetoacetate, acetylacetone, and cyanide anion to acryloylferrocene is described.Reaction was promoted by a catalyst in situ generated from a sacrificial zirconium anode.Diethyl 2,2-bis(3-ferrocenyl-3-oxopropyl)malonate, a new compound, was completely characterized by spectral, physical and crystallographic data.Other obtained compounds were identified by comparison of their spectral and physical data with those published elsewhere. 

Erratum: Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Clinical significance of extrapulmonary tuberculosis in the differential diagnosis of fever of unknown

Tuberkuloza predstavlja infekciju humanim sojem mikobakterije Mycobacterium tuberculosis uz pojavu karakteristiĉnog imunološkog odgovora organizma. Najĉešća forma bolesti je plućna. Po procenama Svetske Zdravstvene Organizacije (SZO) vanplućna tuberkuloza (VPTB) ĉini oko 20-25% formi bolesti. Zbog uglavnom atipiĉne kliniĉke slike (izuzimajući tuberkulozni meningitis), produţenog toka u kome su uz progresivno pogoršanje opšteg stanja, prisutni još samo povišena temperatura i ĉesto pozitivan zapaljenski sindrom, najveći broj ovih bolesnika se razmatra u toku diferencijalne dijagnoze nejasnog febrilnog stanja (NFS). Poseban problem predstavlja teţa dijagnostika VPTB i potreba za ĉešćim korišćenjem invazivne dijagnostike. U periodu do pojave virusa humane imunodeficijencije (HIV) incidenca tuberkuloze u svetu je bila u opadanju, ali se od osamdesetih godina dvadesetog veka tuberkuloza ponovo nameće kao bolest od rastućeg interesa. Procenjuje se da je u svetu oko dve milijarde ljudi inficiranih bacilom M. tuberculosis od kojih je oko 8 miliona godišnje razvije aktivnu tuberkulozu, a oko 2 miliona umre. Incidenca oboljevanja od tuberkuloze i VPTB je u porastu svugde u svetu i u HIV negativnoj populaciji. U takvim okolnostima raste i znaĉaj informisanosti lekara dijagnostiĉara, da se u toku dijagnostiĉkog postupka febrilnog stanja mora razmatrati i tuberkulozna infekcija, kako pluća, tako i vanplućna. Tuberkuloza moţe zahvatiti bilo koji organ u organizmu, s’tim da je plućna lokalizacija najĉešća. Terminom VPTB se oznaĉava izolovana pojava tuberkuloze na bilo kom mestu u organizmu van pluća. Ako je uz vanplućnu lokalizaciju prisutna i zahvaćenost pluća takvi se pacijenti kategorizuju pod dijagnozom plućne tuberkuloze. Varijeteti kliniĉke slike VPTB su mnogobrojni što oteţava dijagnostiku. Uz retke lokalizacije koje daju karakteristiĉne simptome i znake (meningitis) ili bar mogu uputiti u pravcu dijagnoze (tuberkulozni limfadenitis), većina drugih, posebno dubokih lokalizacija se manifestuje samo povišenom temperaturom. Zbog ovakvih teškoća u dijagnostici, proporcionalno je veća zastupljenost VPTB u ukupnom broju otkrivenih bolesnika sa tuberkulozom u tercijarnim ustanovama, nego u primarnoj zdravstvenoj zaštiti...Tuberculosis is an infection with human mycobacteria strain of Mycobacterium tuberculosis, with the occurrence of the characteristic immune response of the organism. The most common form is lung disease. According to estimates by the World Health Organization (WHO), extrapulmonary tuberculosis (EPTB) accounts for 20-25% of the tuberculosis. Mainly due to atypical clinical features (except for tuberculous meningitis), the prolong course of the illness with progressive deterioration of general condition, present only with fever and often positive inflammatory syndrome, most of theses patients are considered in the differential diagnosis of fever of unknown origin (FUO). A particular problem is a difficult diagnosis of EPTB and the need for more frequent use of invasive diagnostic. Until the appearance of human immunodeficiency virus (HIV) incidence of tuberculosis in the world was in decline, but since the eighties of the twentieth century, tuberculosis re-imposed as a disease of growing interest. It is estimated that the world's two billion people infected with an M. tuberculosis, of which about 8 million develop active TB annually, and about 2 million die. The incidence of tuberculosis and EPTB is increasing everywhere in the world and in the HIV negative population too. In such circumstances, medical doctors must have growing awareness of the importance of tuberculosis infection, both lung and extrapulmonary during the diagnostic procedure in febrile conditions. Tuberculosis can affect any organ in the body; however, the most frequent localization is pulmonary. The term EPTB means an isolated occurrence of tuberculosis anywhere in the body outside the lungs. If present with extrapulmonary localization and involvement of the lungs such patients are categorized under the diagnosis of pulmonary tuberculosis. Varieties of clinical presentations of EPTB are numerous which makes diagnosis difficult. With rare localization which give the characteristic signs and symptoms (meningitis), or at least can make towards the diagnosis (tuberculous lymphadenitis), most of the others, especially the deep localization is only manifested with fever. Because of these difficulties in diagnosis, the greater proportion EPTB was detected in tertiary institutions, instead in primary care. The most common localization of EPTB is tuberculosis of the lymph nodes, genitourinary tuberculosis, abdominal tuberculosis, pleural tuberculosis, tuberculous pericarditis, neurotuberculosis, tuberculosis of bones and joints. Other forms of EPTB occur less frequently..

New ferrocene containing 3-(arylthio)propan-1-ones: Synthesis, spectral characterization and crystal structure of 3-[(4-chlorophenyl)thio]-1-ferrocenylpropan-1-one, 3-[(4-chlorophenyl)thio]-1-ferrocenyl-3-phenylpropan-1-one and 3-[(4-chlorophenyl)thio]-3-ferrocenyl-1-phenylpropan-1-one

Three series of ferrocene containing 3-(arylthio)propan-1-ones (each of eight examples) have been synthesized by thia-Michael addition of the corresponding thiophenols to acryloylferrocene, 1-ferroceny1-3-phenylprop-2-en-1-one and 3-ferrocenyl-1-phenylprop-2-en-1-one promoted by the catalyst generated from a sacrificial zirconium anode. All the newly synthesized compounds (16 in total) were characterized by spectral data, whereas single crystal X-ray structure analysis was performed for 3-[(4-chlorophenyl)thio]-1-ferrocenylpropan-1-one (1h), 3-[(4-chlorophenyl)thio]-1-ferrocenyl-3-phenylpropan-1 one (2h) and 3-[(4-chlorophenyl)thio]-3-ferrocenyl-1-phenylpropan-1-one (3h). Molecular geometry and structural characteristics of three thiaketones (1h, 2h and 3h) were analysed and compared in detail. It was found that all three molecules do not form classical H-bonds and pi center dot center dot center dot pi interactions (regardless of the presence of 3 or 4 aromatic rings per a molecule). However, all three crystal structures abound in intermolecular C-H center dot center dot center dot pi interactions while 2h and 3h in addition form intramolecular C-H center dot center dot center dot pi as only evident interaction within the molecules. (C) 2013 Elsevier Ltd. All rights reserved

Nucleation and early stages of growth of lead onto copper electrodes from dilute electrolytes

The processes of nucleation and growth of lead from the dilute electrolytes on copper substrates were investigated by chronoamperometry and by scanning electron microscopic (SEM) analysis of the deposits obtained in the potentiostatic regime of electrolysis. In the dependence of electrodeposition conditions, the nucleation of Pb followed either progressive or instantaneous type. The type of nucleation changed from progressive to instantaneous one with increasing the concentration of Pb(II) ions and the overpotential of electrodeposition. Regardless of the type nucleation, a novel type of Pb particles like cobweb was formed by the potentiostatic electrodeposition in the moment of nucleation and at the early stages of growth. On the basis of the shape of cobweb-like particles and the electrodeposition conditions leading to their formation, these particles were situated in the group of spongy-like ones. Also, comparative morphological analysis of Pb deposits obtained in the conditions of progressive and instantaneous nucleation confirmed the existence of two limiting types of nucleation