Dismal prognosis of Pneumocystis jirovecii pneumonia in patients with multiple myeloma.

Patients with multiple myeloma (MM) are at high risk for infections, including opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP). We conducted a retrospective analysis of patients with MM developing PJP over a 6-year period between January 2016 and December 2021 at the University Hospital of Würzburg by screening cases of microbiologically documented PJP. A total of 201 positive results for P. jirovecii in respiratory specimens were retrospectively retrieved through our microbiology database. Of these cases, 13 patients with MM fulfilled the definition of probable PJP according to EORTC fungal disease definitions. We observed two peaks in PJP incidence, one after stem cell transplantation during first-line treatment (n = 5) and the other in heavily pretreated patients with six or more prior lines of therapy (n = 6). There was high morbidity with nine (69%) patients admitted to the ICU, seven of whom (78%) required mechanical ventilation, and high mortality (62%, n = 8). Notably, only two of the 13 patients (15%) had received PJP prophylaxis. The main reason for discontinuation of prophylaxis with trimethoprim-sulfamethoxazole was grade IV neutropenia. The observed morbidity and mortality of PJP in MM patients are significant and even higher than reported for patients with other hematologic malignancies. According to most current guidelines, the use of prophylaxis would have been clearly recommended in no more than three (23%) of the 13 patients. This illustrates the need to critically reconsider the indications for PJP prophylaxis, which remain incompletely defined.

Quantification of A. fumigatus-specific CD154+ T-cells-preanalytic considerations.

Fungal specific CD154+ T-cells have been described as a biomarker in invasive aspergillosis. The influence of sample storage on the detection of these cells was assessed. Six-hour delay prior to PBMC isolation is associated with an 18% decrease of cell viability and alterations of the cellular composition of the sample. This results in 87% reduction of CD154+ A. fumigatus specific cells due to reduced assay sensitivity and increased background values in unstimulated samples. If prompt cell measurement is not feasible, isolated PBMCs can be frozen (at -20°C and -80°C) and processed later with comparable assay reliability (mean value fresh vs. thawing: 0.126, 0.133; Pearson-Coefficient: 0.962).

Towards loss compensated and lasing terahertz metamaterials based on optically pumped graphene.

We evidence by numerical calculations that optically pumped graphene is suitable for compensating inherent loss in terahertz (THz) metamaterials. We calculate the complex conductivity of graphene under optical pumping and determine the proper conditions for terahertz amplification in single layer graphene. It is shown that amplification in graphene occurs up to room temperature for moderate pump intensities at telecommunication wavelength λ = 1.5 µm. Furthermore, we investigate the coupling between a plasmonic split ring resonator (SRR) metamaterial and optically pumped graphene at a temperature T = 77 K and a pump intensity I = 300 mW/mm(2). We find that the loss of a SRR metamaterial can be compensated by optically stimulated amplification in graphene. Moreover, we show that a hybrid material consisting of asymmetric split-ring resonators and optically pumped graphene can emit coherent THz radiation at minimum output power levels of 60 nW/mm(2).

[Correlation of patients age on length of stay and admission rate in a German emergency department]. / Auswirkungen des patientenalters auf aufenthaltszeiten und stationäre aufnahmen in einer deutschen interdisziplinären notaufnahme.

BACKGROUND: This study aimed to examine correlations between patient age, length-of-stay (LOS) in the emergency department (ED), admission rate for various medical disciplines and probabilities of admission in a German interdisciplinary ED. PATIENTS AND METHODS: In a retrospective cohort analysis, 7937 patients of the ED were evaluated for age, gender, ED-LOS and admission rate. Rank correlation coefficients were calculated in order to analyze the influence of patient age for each discipline. Statistical tests were performed to evaluate explorative hypotheses on specific discipline influence of patient age. RESULTS: Patients age significantly differed between the disciplines. There was a strong correlation between patient age and LOS for trauma surgery, visceral surgery and ophthalmology. The correlation between patient age and admission rate was highest in patients with problems regarding internal medicine, trauma surgery and neurology. CONCLUSION: There is a correlation between patients age, LOS and admission rate in the ED.

Porphyry-copper ore shells form at stable pressure-temperature fronts within dynamic fluid plumes.

Porphyry-type ore deposits are major resources of copper and gold, precipitated from fluids expelled by crustal magma chambers. The metals are typically concentrated in confined ore shells within vertically extensive vein networks, formed through hydraulic fracturing of rock by ascending fluids. Numerical modeling shows that dynamic permeability responses to magmatic fluid expulsion can stabilize a front of metal precipitation at the boundary between lithostatically pressured up-flow of hot magmatic fluids and hydrostatically pressured convection of cooler meteoric fluids. The balance between focused heat advection and lateral cooling controls the most important economic characteristics, including size, shape, and ore grade. This self-sustaining process may extend to epithermal gold deposits, venting at active volcanoes, and regions with the potential for geothermal energy production.

Dietary P regulates phosphate transporter expression, phosphatase activity, and effluent P partitioning in trout culture.

Phosphate utilization by fish is an important issue because of its critical roles in fish growth and aquatic environmental pollution. High dietary phosphorus (P) levels typically decrease the efficiency of P utilization, thereby increasing the amount of P excreted as metabolic waste in effluents emanating from rainbow trout aquaculture. In mammals, vitamin D3 is a known regulator of P utilization but in fish, its regulatory role is unclear. Moreover, the effects of dietary P and vitamin D3 on expression of enzymatic and transport systems potentially involved in phosphate utilization are little known. We therefore monitored production of effluent P, levels of plasma vitamin D3 metabolites, as well as expression of phosphatases and the sodium phosphate cotransporter (NaPi2) in trout fed semipu diets that varied in dietary P and vitamin D3 levels. Mean soluble P concentrations varied markedly with dietary P but not with vitamin D3, and constituted 40-70% of total effluent P production by trout. Particulate P concentrations accounted for 25-50% of effluent P production, but did not vary with dietary P or vitamin D3. P in settleable wastes accounted for <10% of effluent P. The stronger effect of dietary P on effluent P levels is paralleled by its striking effects on phosphatases and NaPi2. The mRNA abundance of the intestinal and renal sodium phosphate transporters increased in fish fed low dietary P; vitamin D3 had no effect. Low-P diets reduced plasma phosphate concentrations. Intracellular phytase activity increased but brushborder alkaline phosphatase activity decreased in the intestine, pyloric caeca, and gills of trout fed diets containing low dietary P. Vitamin D3 had no effect on enzyme activities. Moreover, plasma concentrations of 25-hydroxyvitamin D3 and of 1,25-dihydroxyvitamin D3 were unaffected by dietary P and vitamin D3 levels. The major regulator of P metabolism, and ultimately of levels of P in the effluent from trout culture, is dietary P.

Release into the environment of metals by two vascular salt marsh plants.

Metals in contaminated salt marshes are mainly locked in the anaerobic layer of sediments, where they are tightly bound as sulfides and organic complexes. Vascular plants survive in saturated soils in part by pumping O2 into their root zones, changing their microenvironment to an oxic one. This, along with chelating exudates, mobilizes metals, allowing uptake by the roots. We compared the common reed Phragmites australis and cordgrass Spartina alterniflora in lab and field studies for ways in which they handle trace metals. Both plants store most of their metal burden in their roots, but some is transported to aboveground tissues. Spartina leaves contain approximately 2-3 x more Cr, Pb, and Hg than Phragmites leaves, but equivalent Cu and Zn. Furthermore, Spartina leaves have salt glands, so leaf excretion of all metals is twice that of Phragmites. In-depth studies with Hg indicate that Hg excretion correlates with Na release but not with transpiration, which is 2.2 x higher in Phragmites; and that more Hg accumulates in early-appearing leaves than in upper (i.e. later) leaves in both species. Spartina thus makes more metals available to salt marsh ecosystems than Phragmites by direct excretion and via dead leaves which will enter the food web as detritus.

Hepatic histopathology in two populations of the mummichog, Fundulus heteroclitus.

The pollution-tolerant mummichog, Fundulus heteroclitus, inhabits a heavily contaminated estuary, Piles Creek (PC), in Linden, NJ. PC contaminants include PAHs, PCBs and many metals, including high Hg and Pb. PC mummichog livers and kidneys were compared with those from a pristine estuary in Tuckerton (TK), NJ, by standard histopathological methods, with quantification by computerized image analysis. PC livers had > 2 x the lipid ratios of TK livers. Cell sizes and shapes were not different between populations. TK livers had a 25% incidence of basophilic areas and an age-related 30% incidence of macrophage aggregates; PC livers had none of these lesions. PC livers had a 100% incidence of necrotic foci, compared with 55% of TK livers. Inflammation was noted in 50% of TK livers but only 27% of PC livers. Curiously, the TK livers had a 45% incidence of metacercarial cysts of a digenetic trematode, while none were found in the PC livers. The TK focal necrosis and macrophage aggregates coincided with parasite infestation. There were no observed kidney lesions in either population. Positive biomarkers in this species thus included high hepatic lipid content, possibly necrosis, but no other lesions. The lack of trematode cysts in PC livers may reflect the lack of an intermediate host in this low biodiversity estuary.

Development of thyroid abnormalities in mummichogs, Fundulus heteroclitus, from a polluted site.

Previous studies showed that adult and 6-month-old young-of-year Fundulus heteroclitus from a polluted site have enlarged thyroid follicles and (in adults) higher thyroxine levels compared to fish from an unpolluted reference site. This study's purpose was to discover when in development these differences begin to appear. For 15-20 mm fish, the average follicle size of the polluted population was significantly larger than that of the reference population, similar to the pattern found in older fish. However, for the smaller size (12-14.5 mm), the average follicle size of fish from the polluted site was significantly smaller. Although not statistically significant, radioimmunoassay measurements of thyroxine levels were consistent with follicle differences: in larger sizes (20-25 and 15-20 mm) fish from the polluted site had higher thyroxine levels but the smaller size (12-14.5 mm) had lower levels. Therefore, the thyroid abnormalities seen in adults begin when the fish are approximately 15-20 mm long. However, the follicle size reversal for the 12-14.5 mm range may also indicate abnormality at that developmental stage.

Lead uptake, distribution, and effects in two dominant salt marsh macrophytes, Spartina alterniflora (cordgrass) and Phragmites australis (common reed).

We examined biomass accumulation, tissue concentrations of lead (Pb), and net uptake of Pb in Phragmites australis (common reed) and Spartina alterniflora (salt cord grass) grown under greenhouse conditions in sediment of different Pb concentrations. Sediment and newly emerged ramets of each plant species were collected in April 1999 from Tuckerton, NJ, a relatively clean salt marsh. One-gallon pots were filled with either control sediment (29 microg g(-1) Pb) or Pb-added sediment (68 microg g(-1) Pb), and the sediment moisture was kept saturated along with controlled additions of additional nutrients. At harvest in October, whole plant biomass was 60-85% greater for pots with P. australis than pots with S. alterniflora and a 40-70% reduction in biomass in response to the addition of Pb was observed for both species. In the high Pb treatments, both concentrations and pools of Pb were greater in the leaves of S. alterniflora than in leaves of P. australis at the end of the growing season. In both species, Pb concentrations were higher in lower leaves than upper leaves. The addition of Pb into experimental pots led to over an 800% increase in Pb standing stock for both species. In S. alterniflora, however, significantly more of this pool was allocated to aboveground biomass (leaves and stems) than to belowground biomass (roots and rhizomes). This difference in allocation was more profound at the higher sediment Pb concentration (Pb-added pots). This fundamental difference between the species in response to Pb contamination indicates that metal export into food webs or the water column should be greater in stands of S. alterniflora than in P. australis. These results suggest that in Pb-contaminated, and possibly all metal-contaminated sediments, the replacement of S. alterniflora with P. australis may reduce metal bioavailability by sequestering a greater proportion of its metal burden in belowground tissues which are likely to be permanently buried.

Dinuclear titanium(IV) complexes from amino acid bridged dicatechol ligands: formation, structure, and conformational analysis.

Amino acid bridged dicatechol ligands 3a-e-H4 form dinuclear double-stranded coordination compounds [(3a-e)2Ti2(OCH3)2]2- with titanium(IV) ions. Due to the directionality of the ligands, the chirality of the strand, and the chiral complex units, up to seven isomers, I-VII, can be obtained for the double-stranded complexes of ligands 3a-e-H4. The composition of the mixture of isomeric compounds in solution is strongly dependent on the conditions of complex formation. Under thermodynamic control, only a few isomers are obtained, one of which is the major component of the mixture. X-ray structure analyses were performed for K2[(3b)2Ti2(OH)2] and K2[(3d)2Ti2(OH)2] (type I), and for the meso complex Na2[(3e)(3e')Ti2(OCH3)2]. A conformational analysis that uses Ramachandrans method revealed that the conformation of the amino acids in the ligand strands can be compared with those found for amino acids in helical peptide structures. The most favored isomer of [(3)2Ti2(OCH3)2]2- appears to be of type I, with the catecholamide unit located at the N terminus of the ligand strand that binds to a lambda-configurated titanium(IV) complex unit and the dihydroxybenzyl group at the C terminus that coordinates to a delta-configurated titanium(IV) complex unit. The lambda configuration at the N terminus induces the conformation of a right-handed helix in the amino acid residue, while the delta configuration induces the less favored left-handed helix.

Calcitermin, a novel antimicrobial peptide isolated from human airway secretions.

The human airways are protected from pathogenic colonization by a blanket of fluid impregnated with innate antimicrobial effector molecules. Among several previously uncharacterized components, we isolated a peptide that had activity primarily targeting Gram-negative bacteria. We named the peptide 'calcitermin' since its amino acid sequence and mass were equivalent to the 15 C-terminal residues of the S100 protein, calgranulin C. The antimicrobial activity of calcitermin was enhanced in acidic buffers (pH 5.4) and in the presence of micromolar concentrations of ZnCl(2). Analysis revealed a putative zinc-binding consensus sequence as well as an alpha-helical conformation in structure-promoting solvents.

Endocrine disruption: thyroid dysfunction in mummichogs (Fundulus heteroclitus) from a polluted habitat.

Mummichogs (Fundulus heteroclitus) from Piles Creeks (PC), New Jersey (a polluted site), are sluggish and show poorer prey capture and predator avoidance than reference fish from Tuckerton (TK). The behavioral dysfunction of the PC fish may be associated with thyroid impairment due to endocrine disruption. In this study, we compared thyroid histology and thyroid hormones in the two populations and determined experimentally whether the polluted environment could alter thyroid hormone levels. PC fish had larger thyroid follicles, greater follicle cell heights, and contained higher plasma thyroxine (T4) levels than TK fish. However, there were no significant differences in either plasma or tissue triiodothyronine (T3). TK fish held in simulated PC environments had higher plasma T4 and lower plasma T3 than field-sampled fish. PC fish held in clean water had lower plasma T4 and T3 than field-sampled fish. In either case, there was no significant difference in tissue T3 content. The contaminants in PC alter thyroid structure and function, which may relate to the behavioral differences between fish from the polluted and reference sites.

Sexually transmitted infections in young pregnant women in Bangui, Central African Republic.

In early 1996, 481 women visiting the antenatal services of the 3 major governmental health centres in the capital city of the Central African Republic (CAR) were included in the study. All study participants underwent the health centre's routine gynaecological examination, including laboratory diagnosis of trichomoniasis, candidiasis, gonorrhoea, syphilis and bacterial vaginosis. Cervical secretions and blood samples from study participants were sent to the National STD Reference Centre for diagnosis of Chlamydia trachomatis, Neisseria gonorrhoeae, Candida albicans, Treponema pallidum, and HIV. Overall, 34% of the study women were diagnosed with at least one sexually transmitted infection (STI) (3.1% N. gonorrhoeae, 6.2% C. trachomatis, 9.9% T. vaginalis, 6.7% T. pallidum, 12.2% HIV-1). In addition, 29.1% of women were diagnosed with bacterial vaginosis and 46.6% with candidiasis. Only a small proportion of these women had sought treatment during the weeks before, despite the recognition of genital symptoms. Self-reported and health worker-recognized symptoms, signs and laboratory results exhibited only low sensitivities, specificities, and positive predictive values in the diagnosis of STIs. These findings confirm the high vulnerability of young African women to STIs and emphasize the need for specific control interventions which should include affordable and user-friendly services. Moreover, these results call for more effective quality control in case of laboratory-based STI control strategies and question the validity of syndromic STI management strategies in women attending antenatal care services in Africa.

PIP: This study reports on the prevalence of sexually transmitted infections (STIs) among pregnant women in Bangui, Central African Republic. A total of 481 pregnant women visiting the antenatal services of the 3 major governmental health centers were included in the study. All these women were interviewed and underwent gynecological examination, including laboratory diagnosis of trichomoniasis, candidiasis, gonorrhea, syphilis and bacterial vaginosis. The results revealed that 34% of the women were diagnosed with at least one STI. Gonorrhea accounted for 3.1%, chlamydiasis for 6.2%, trichomoniasis for 9.9%, syphilis for 6.7%, and HIV-1 for 12.2%. In addition, 29.1% of women were diagnosed with bacterial vaginosis and 46.6% with candidiasis. The majority of the women diagnosed with an STI reported specific clinical symptoms during the week before they entered into the study, but only a minority of them actively sought treatment, and only half of those consulted the formal health sector. Self-reported and health worker-recognized symptoms, signs and laboratory results manifested only low sensitivities, specificities, and positive predictive values in STI diagnosis. These results confirmed the high susceptibility of young African women to STIs. Therefore, specific control interventions should be carried out which incorporate affordable and user-friendly services.

Application of the ParaSight-F dipstick test for malaria diagnosis in a district control program.

A rapid test for the diagnosis of Plasmodium falciparum infections based on the detection of histidine-rich-protein II, the ParaSight-F test, was evaluated after introduction in a district malaria control program in Uganda. Suspected treatment failures, pregnant women and infants with clinical malaria and general fever cases were tested at health facilities in malaria hypo-, meso- and holoendemic areas. A total of 1326 tests were carried out by health unit staff, cross read by experienced laboratory staff and results compared with thick film microscopy as the standard. Rater agreement in reading the dipstick result between health unit staff and laboratory staff was high, kappa index 0.94 (0.88-0.99). Sensitivity was 99.6% (99.0-100) for parasite densities above 500/microl, 98.6% (97.7-99.6) for densities above 50/microl and 22.2% (8.6-42.3) for densities below 10/microl. With the applied testing strategies no differences were found between endemicity levels or patient categories. Specificity was 86.2% (83.3-88.8) overall, but significantly higher in general fever cases (92.7%) compared to the other patient groups (84.3%, P=0.009). At the given prevalences positive predictive values (ppv) were above 80% and negative predictive values (npv) above 90% in all cases except in pregnant women (ppv: 77.8%). We conclude that in certain situations this test is an alternative to microscopy to improve diagnostic facilities for case management in malaria control programs in endemic African countries.

Reductions in risk behaviour provide the most consistent explanation for declining HIV-1 prevalence in Uganda.

OBJECTIVE: To monitor the HIV-1 epidemic in Western Uganda and the possible impact of interventions. DESIGN: Results from sentinel surveillance of HIV-1 seroprevalence were compared with cross-sectional serosurvey data and model simulations. METHODS: Age-specific trends in HIV-1 prevalence between 1991 and 1997 amongst antenatal clinic (ANC) attenders in the town of Fort Portal, where a comprehensive AIDS control programme has been implemented since 1991, were analysed. Results were compared with outputs from a mathematical model simulating the HIV-1 epidemic in Uganda. Two scenarios were modelled: one without and one with behaviour change. Sentinel surveillance data were compared with data from a population-based HIV-1 serosurvey at the study site, which was carried out in early 1995. RESULTS: Data from 3271 ANC attenders identified greater education and being single as risk factors for HIV-1 infection. A significant decrease of risk for women with secondary school education over time was observed, whereas the risk for illiterate women remained high. Among women aged 15-19 years (n = 1045) education and marital status-adjusted HIV-1 prevalence declined steadily from 32.2% in 1991 to 10.3% in 1997. For 20-24-year-old women (n = 1010) HIV-1 prevalence increased until 1993 from 19.9% to 31.7% and decreased thereafter (21.7% in 1997). These trends closely follow the prediction of the model simulation assuming behaviour change, and for 1995-1997, confidence intervals of the HIV-1 prevalence estimate exclude the model output for an uninfluenced epidemic. No clear trends of HIV-1 prevalence were found in older women (n = 1216) and comparisons with the model were ambiguous. Sentinel surveillance data at the time of the population survey closely reflected results for the female general population sample for the two younger age-groups (15-19 and 20-24 years). In contrast, pregnant women aged 25-29 years showed significantly lower rates than the population sample (20.8% versus 45.1%). CONCLUSION: HIV-1 prevalence amongst ANC attenders aged 15-24 years can be used to monitor the HIV-1 epidemic in the given setting. Declining trends of HIV-1 prevalence in women aged 15-19 and 20-24 years most likely correspond to a reduced HIV-1 incidence attributable to changes in behaviour. Our data also show that sentinel surveillance data need to be age-stratified to give useful information.