Challenges in the Long-term Management of Patients With Coccidioidal Meningitis: A Retrospective Analysis of Treatment and Outcomes.

Background: Coccidioidal meningitis (CM) is the most severe form of disseminated coccidioidomycosis. Despite years of clinical experience, it remains a difficult condition to treat, often requiring surgical procedures, such as placement of a ventriculoperitoneal shunt, in addition to lifelong antifungal therapy. Methods: We performed a retrospective analysis of patients with CM seen in a large referral center in Central Valley, California, from 2010 to 2020. Data pertinent to CM were collected and analyzed. Results: Among 133 patients with CM identified in the 10-year period, nonadherence to antifungal therapy was noted in 43% of patients. Of the 80 patients who underwent ventriculoperitoneal shunt placement for management of intracranial pressure, shunt failure requiring revision surgery occurred in 42 (52.5%). Rehospitalizations due to CM-related reasons occurred in 78 of 133 patients (59%). Twenty-three percent of patients (n = 29) died due to complications from CM, on an average 22 months after the diagnosis of CM. Encephalopathy at presentation was associated with a significantly higher risk of death. Conclusions: Patients with CM in central California are predominantly rural agricultural workers with elevated levels of poverty and low health literacy and many barriers to care, leading to high rates of medication nonadherence and loss to follow-up outpatient care. Management challenges are frequent, such as failure of antifungal therapy, high rates of rehospitalization, and the need for repeated shunt revision surgeries. In addition to the development of curative new antifungal agents, understanding the barriers to patient adherence to care and antifungal therapy and identifying means to overcome such barriers are of paramount importance.

Water accounting as a tool for tracing the industries responsible for the point-source loads into water bodies.

Returning flows of water from the economy to the environment, particularly wastewaters, are highly important contributors to the quality of freshwater resources and the health of aquatic ecosystems. While the total loads of various harmful substances received by wastewater treatment facilities are often measured and reported, the origins of these loads are generally not allocated to specific industries. Instead, they pass from treatment facilities to the environment and are thus simply attributed to arising from the sewerage industry. In this study, we introduce a method for employing high-quality water accounting of the phosphorous and nitrogen loads and apply it to the Finnish economy. We also introduce a means for assessing the quality of the resulting accountancies and, for our Finnish case study, we show a close correspondence between independent top-down and bottom-up calculations, indicating the figures are highly reliable. We thus conclude, firstly, that the presented methodology can produce versatile and reliable data on different wastewater-related loads in the water; secondly, that such data can assist in developing appropriate mitigation strategies; and, thirdly, that the data may also be applied in further sustainability analyses, such as in environmentally extended input-output modelling.

Spinal Arachnoiditis in Patients with Coccidioidomycosis Meningitis-Analysis of Clinical and Imaging Features.

Background: Coccidioidomycosis meningitis (CM) is the most aggressive form of coccidioidomycosis, requiring lifelong antifungal treatment and often cerebrospinal fluid (CSF) diversion. Long-standing CM can be associated with spinal complications such as arachnoiditis. However, studies describing the frequency, clinical, and imaging characteristics of arachnoiditis in patients with CM are limited. Methods: We identified 133 patients with CM based on CSF culture, PCR, or serology between January 2010 and December 2020. Of these, 37 patients underwent spinal imaging. Data on demographics, risk factors, symptoms, antifungal therapy, surgical management, follow-up visits, adherence, serological trends, and imaging findings were reviewed. Results: Abnormal findings were observed in 30 of the 37 patients with CM who underwent spinal imaging. The imaging abnormalities noted in our study included leptomeningeal enhancement (53%), arachnoiditis (53%), syringomyelia (23%), cord signal abnormalities (10%), and osteomyelitis (7%). Of the 30 patients, 90% had symptoms, such as weakness, numbness, or urinary retention. The incidence of arachnoiditis in the present study was 12%. Higher initial CSF protein levels and intra cranial pressure were associated with a higher risk of developing arachnoiditis/syringomyelia. Management of CM was challenging, as evidenced by shunt failure (46%), medication non-compliance (57%), and lack of adequate follow-up (60%). Persistent disabilities were noted in 62% of the patients. Conclusions: Patients with CM develop spinal complications such as arachnoiditis, or syringomyelia. Many cases may go undetected due to lack of symptoms in early stages. CM management challenges such as shunt failure, lack of follow-up care, and medication noncompliance, were frequent.

Strongyloides Hyperinfection Syndrome among COVID-19 Patients Treated with Corticosteroids.

Widespread use of corticosteroids for COVID-19 treatment has led to Strongyloides reactivation and severe disease in patients from endemic areas. We describe a US patient with COVID-19 and Strongyloides hyperinfection syndrome and review other reported cases. Our findings highlight the need for Strongyloides screening and treatment in high-risk populations.

Disseminated Gonorrhea Presenting as Liver Abscess in a Patient With Sickle Cell Disease.

ABSTRACT: Infection caused by Neisseria gonorrhoeae is a global health concern. Occasionally, gonococcal infections may disseminate and cause clinical syndromes, such as arthritis, tenosynovitis, and skin lesions. Here, we report a very rare presentation of a liver abscess due to N. gonorrhoeae in a 29-year-old woman with sickle cell disease without prior genitourinary complaints. The patient was successfully treated using drainage and antimicrobial therapy. Evaluation did not reveal any inherited defects in complement deficiency. It is possible that the underlying immune defects from sickle cell disease and unknown bacterial virulence factors could have contributed to this dissemination. Further research is needed to understand the immunopathogenesis of disseminated gonococcal infections, and efforts to screen and prevent primary infections are ongoing.

Coccidioidal meningitis and neurosyphilis co-infection in a non-HIV patient.

Coccidioides sp. and Treponema pallidum can both cause infections of the central nervous system if untreated. We describe a case of an immunocompetent patient living in an endemic region for Coccidioides who presented with headaches and diplopia and was found to have co-infection of coccidioidal meningitis and neurosyphilis. We highlight the importance of evaluation for CNS co-infections as they may be underdiagnosed, especially in endemic areas for coccidioidomycosis.

Polarization and Phase Textures in Lattice Plasmon Condensates.

Polarization textures of light may reflect fundamental phenomena, such as topological defects, and can be utilized in engineering light beams. They have been observed, for instance, in photonic crystal lasers and semiconductor polariton condensates. Here we demonstrate domain wall polarization textures in a plasmonic lattice Bose-Einstein condensate. A key ingredient of the textures is found to be a condensate phase that varies spatially in a nontrivial manner. The phase of the Bose-Einstein condensate is reconstructed from the real- and Fourier-space images using a phase retrieval algorithm. We introduce a simple theoretical model that captures the results and can be used for design of the polarization patterns and demonstrate that the textures can be optically switched. The results open new prospects for fundamental studies of non-equilibrium condensation and sources of polarization-structured beams.

Appearance of congenital hand anomalies.

BACKGROUND AND OBJECTIVE: Impact of appearance of congenital hand anomalies has not previously been reported. The purpose of this study was to describe the common perception about how different congenitally malformed hands look. METHODS: We developed a questionnaire in a game format to evaluate the appearance of different hands. Altogether 1450 (954 females) 4- to 84-year-old residents (296 children) of two European and one Asian (n = 102) country were asked to rate the appearance of different looking hands on a five-point pictorial Likert-type scale. Standardized photographs of the dorsal aspect of 17 different congenitally malformed non-operated hands and a normal hand were presented to respondents. Significance of age, gender, nationality, and profession of the respondents was assessed. RESULTS: The respondents' ranking order of the hands was nearly consistent. The normal hand (mean = 4.43, standard deviation = 0.85, Md = 5) and clinodactyly (mean = 4.37, standard deviation = 0.86, Md = 5) were perceived to have the best appearance. Symbrachydactyly (mean = 1.42, standard deviation = 0.68, Md = 1) and radial club hand (mean = 1.40, standard deviation = 0.68, Md = 1) received the lowest scores. Adults rated the appearance of hands higher than children regarding 14 hands, females higher than men regarding 15 hands, and Europeans higher than Asians in 4 hands (p < 0.05, respectively). Europeans rated four-finger hand (mean = 3.21, standard deviation = 1.18, Md = 3) better looking than six-finger hand (mean = 2.92, standard deviation = 1.18, Md = 3, p < 0.005), whereas Asians gave higher scores to six-finger hand (mean = 2.66, standard deviation = 1.26, Md = 3) compared to four-finger hand (mean = 2.51, standard deviation = 1.14, Md = 2). Medical doctors and nurses gave higher scores compared to the other profession groups, school children, and high school students in five hands (p < 0.05). CONCLUSIONS: A normal hand is perceived distinctly better looking than most congenitally different hands. Different malformations' appearance was ranked very coherently in the same order despite of participants' age, gender, nationality, or profession. Asians seem to prefer an additional digit to a four-finger hand.

Spatial and Temporal Coherence in Strongly Coupled Plasmonic Bose-Einstein Condensates.

We report first-order spatial and temporal correlations in strongly coupled plasmonic Bose-Einstein condensates. The condensate is large, more than 20 times the spatial coherence length of the polaritons in the uncondensed system and 100 times the healing length, making plasmonic lattices an attractive platform for studying long-range spatial correlations in two dimensions. We find that both spatial and temporal coherence display nonexponential decay; the results suggest power-law or stretched exponential behavior with different exponents for spatial and temporal correlation decays.

The type of the functional cardiovascular response to upright posture is associated with arterial stiffness: a cross-sectional study in 470 volunteers.

BACKGROUND: In a cross-sectional study we examined whether the haemodynamic response to upright posture could be divided into different functional phenotypes, and whether the observed phenotypes were associated with known determinants of cardiovascular risk. METHODS: Volunteers (n = 470) without medication with cardiovascular effects were examined using radial pulse wave analysis, whole-body impedance cardiography, and heart rate variability analysis. Based on the passive head-up tilt induced changes in systemic vascular resistance and cardiac output, the principal determinants of blood pressure, a cluster analysis was performed. RESULTS: The haemodynamic response could be clustered into 3 categories: upright increase in vascular resistance and decrease in cardiac output were greatest in the first (+45 % and -27 %, respectively), smallest in the second (+2 % and -2 %, respectively), and intermediate (+22 % and -13 %, respectively) in the third group. These groups were named as 'constrictor' (n = 109), 'sustainer' (n = 222), and 'intermediate' (n = 139) phenotypes, respectively. The sustainers were characterized by male predominance, higher body mass index, blood pressure, and also by higher pulse wave velocity, an index of large arterial stiffness, than the other groups (p < 0.01 for all). Heart rate variability analysis showed higher supine and upright low frequency/high frequency (LF/HF) ratio in the sustainers than constrictors, indicating increased sympathovagal balance. Upright LF/HF ratio was also higher in the sustainer than intermediate group. In multivariate analysis, independent explanatory factors for higher pulse wave velocity were the sustainer (p < 0.022) and intermediate phenotypes (p < 0.046), age (p < 0.001), body mass index (p < 0.001), and hypertension (p < 0.001). CONCLUSIONS: The response to upright posture could be clustered to 3 functional phenotypes. The sustainer phenotype, with smallest upright decrease in cardiac output and highest sympathovagal balance, was independently associated with increased large arterial stiffness. These results indicate an association of the functional haemodynamic phenotype with an acknowledged marker of cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT01742702.

Ethanol-based in situ bioremediation of acidified, nitrate-contaminated groundwater.

A novel approach for the in situ bioremediation of acidified, nitrate-contaminated groundwater was developed. Ethanol was introduced into the groundwater to enhance the activity of intrinsic denitrifying micro-organisms. Infiltration of the carbon source was made via an infiltration gallery constructed in the unsaturated zone to avoid clogging problems and to allow wider distribution of ethanol in the groundwater. The changes in the groundwater geochemistry and soil gas composition were monitored at the site to evaluate the efficiencies of the infiltration system and nitrate removal. Moreover, the impact of pH and ethanol addition on the denitrification rate was studied in laboratory. A reduction of 95% was achieved in the groundwater nitrate concentrations during the study. Neither clogging problems nor inefficient introduction of ethanol into the saturated zone were observed. Most crucial to the denitrifying communities was pH, values above 6 were required for efficient denitrification.

Nicotinamide mononucleotide adenylyltransferase2 overexpression enhances colorectal cancer cell-kill by Tiazofurin.

Colorectal cancer cells exhibit limited cytotoxicity towards Tiazofurin, a pro-drug metabolized by cytosolic nicotinamide mononucleotide adenylyltransferase2 (NMNAT2) to thiazole-4-carboxamide adenine dinucleotide, a potent inhibitor of inosine 5'-monophosphate dehydrogenase required for cellular guanylate synthesis. We tested the hypothesis that colorectal cancer cells that exhibit low levels of NMNAT2 and are refractory to Tiazofurin can be rendered sensitive to Tiazofurin by overexpressing NMNAT2. Transfection of hNMNAT2 resulted in a six- and threefold cytoplasmic overexpression in Caco2 and HT29 cell lines correlating with Tiazofurin-induced enhanced cell-kill. Folate receptors expressed on the cell surface of 30-50% colorectal carcinomas were exploited for cellular targeting with Tiazofurin encapsulated in folate-tethered nanoparticles. Our results indicated that in wild-type colorectal cancer cells, free Tiazofurin-induced EC50 cell-kill was 1500-2000 µM, which was reduced to 66-156 µM in hNMNAT2-overexpressed cells treated with Tiazofurin encapsulated in non-targeted nanoparticles. This efficacy was improved threefold by encapsulating Tiazofurin in folate-tethered nanoparticles to obtain an EC(50) cell-kill of 22-59 µM, an equivalent of 100-300 mg m(-2) (one-tenth of the approved dose of Tiazofurin in humans), which will result in minimal toxicity leading to cancer cell-kill. This proof-of-principle study suggests that resistance of colorectal cancer cell-kill to Tiazofurin can be overcome by sequentially overexpressing hNMNAT2 and then facilitating the uptake of Tiazofurin by folate-tethered nanoparticles, which enter cells via folate receptors.

Metabolic syndrome may be associated with increased arterial stiffness even in the absence of hypertension: a study in 84 cases and 82 controls.

OBJECTIVE: To evaluate the hemodynamic characteristics of metabolic syndrome (MetS) in the absence and presence of hypertension. MATERIALS/METHODS: Altogether 166 subjects without previously diagnosed cardiovascular disease, diabetes, or antihypertensive medication, were allocated to four groups: control, hypertension only, MetS without hypertension, and MetS with hypertension (mean age 44-46 years). Cut-point for hypertension was blood pressure ≥140/90 mmHg. Other criteria of MetS were as defined by Alberti et al. 2009. Hemodynamic variables were measured using whole-body impedance cardiography and pulse wave analysis. RESULTS: Pulse wave velocity was higher in hypertensive and normotensive subjects with MetS than controls (p<0.05), and in the hypertensive MetS group than subjects with hypertension only (p<0.05). Aortic pulse pressure was higher in the two hypertensive groups than the two normotensive groups (p<0.05). Systemic vascular resistance index was higher in the hypertensive than normotensive MetS group (p<0.05), and in the group with hypertension alone than in controls (p<0.05). Heart rate was higher in the hypertensive Mets group than in controls and subjects with hypertension only (p<0.05). Cardiac index did not differ, while stroke index was lower in both groups with MetS than groups without MetS. Augmentation pressure was higher in the hypertensive MetS group than in controls and normotensive MetS group (p<0.05). CONCLUSIONS: Pulse wave velocity, an acknowledged marker of arterial stiffness, was associated with MetS even in the absence of hypertension. This emphasizes the importance of the prevention and treatment of MetS.

Surface properties and interaction forces of biopolymer-doped conductive polypyrrole surfaces by atomic force microscopy.

Surface properties and electrical charges are critical factors elucidating cell interactions on biomaterial surfaces. The surface potential distribution and the nanoscopic and microscopic surface elasticity of organic polypyrrole-hyaluronic acid (PPy-HA) were studied by atomic force microscopy (AFM) in a fluid environment in order to explain the observed enhancement in the attachment of human adipose stem cells on positively charged PPy-HA films. The electrostatic force between the AFM tip and a charged PPy-HA surface, the tip-sample adhesion force, and elastic moduli were estimated from the AFM force curves, and the data were fitted to electrostatic double-layer and elastic contact models. The surface potential of the charged and dried PPy-HA films was assessed with Kelvin probe force microscopy (KPFM), and the KPFM data were correlated to the fluid AFM data. The surface charge distribution and elasticity were both found to correlate well with the nodular morphology of PPy-HA and to be sensitive to the electrochemical charging conditions. Furthermore, a significant change in the adhesion was detected when the surface was electrochemically charged positive. The results highlight the potential of positively charged PPy-HA as a coating material to enhance the stem cell response in tissue-engineering scaffolds.

Strategy for naturelike designer transcription factors with reduced toxicity.

For clinical applications, the biological functions of DNA-binding proteins require that they interact with their target binding site with high affinity and specificity. Advances in randomized production and target-oriented selection of engineered artificial DNA-binding domains incited a rapidly expanding field of designer transcription factors (TFs). Engineered transcription factors are used in zinc-finger nuclease (ZFN) technology that allows targeted genome editing. Zinc-finger-binding domains fabricated by modular assembly display an unexpectedly high failure rate having either a lack of activity as ZFNs in human cells or activity at "off-target” binding sites on the human genome causing cell death. To address these shortcomings, we created new binding domains using a targeted modification strategy. We produced two SP1 mutants by exchanging amino acid residues in the alpha-helical region of the transcription factor SP1. We identified their best target binding sites and searched the NCBI HuRef genome for matches of the nine-base-pair consensus binding site of SP1 and the best binding sites of its mutants. Our research concludes that we can alter the binding preference of existing zinc-finger domains without altering its biological functionalities.

Structural and functional characteristics of chimeric avidins physically adsorbed onto functionalized polythiophene thin films.

Stabilized bioreceptor layers are of great importance in the design of novel biosensors. In earlier work, chimeric avidins enabled immobilization of biotinylated antibodies onto gold surfaces with greater stability compared to more conventional avidins (wild-type avidin and streptavidin). In the present study, the applicability of chimeric avidins as a general binding scaffold for biotinylated antibodies on spin-coated functionalized polythiophene thin films has been studied by surface plasmon resonance and atomic force microscopy. Novel chimeric avidins showed remarkably increased binding characteristics compared with other avidins, such as wild-type avidin, streptavidin, and bacterial avidin when merely physically adsorbed onto the polythiophene surface. They gave the highest binding capacities, the highest affinity constant, and the highest stability for biotinylated probe immobilization. Introduction of carboxylic acid groups to polythiophene layer further enhanced the binding level of the avidins. Polythiophene layers functionalized with chimeric avidins thus offered a promising generic platform for biosensor applications.

Monitored natural attenuation.

Monitored natural attenuation (MNA) is an in situ remediation technology that relies on naturally occurring and demonstrable processes in soil and groundwater which reduce the mass and concentration of the contaminants. Natural attenuation (NA) involves both aerobic and anaerobic degradation of the contaminants due to the fact that oxygen is used up near the core of the contaminant plume. The aerobic and anaerobic microbial processes can be assessed by microbial activity measurements and molecular biology methods in combination with chemical analyses. The sampling and knowledge on the site conditions are of major importance for the linkage of the results obtained to the conditions in situ. Rates obtained from activity measurements can, with certain limitations, be used in modeling of the fate of contaminants whereas most molecular methods mainly give qualitative information on the microbial community and gene abundances. However, molecular biology methods are fast and describe the in situ communities and avoid the biases inherent to activity assays requiring laboratory incubations.

Evaluation of the bactec MGIT 960 TB system for recovery and identification of Mycobacterium tuberculosis complex in a high through put tertiary care centre.

AIM: To evaluate the performance of an automated BACTEC MGIT 960, a non-radioactive, non-invasive liquid culture system for cultivation of M. tuberculosis complex in terms of recovery rate and time. MATERIALS AND METHODS: From March 2005 to December 2007, 14,597 specimens were processed using the MGIT 960 system and the results were compared with conventional L.J medium. We standardised r-nitro benzoic acid (PNBA) assay on MGIT 960 TB system for identification of M. tuberculosis complex and evaluated its usefulness by comparing the results with an in-house molecular assay and sequencing. RESULTS AND DISCUSSION: Of the total 6143 (42%) isolates positive for M. tuberculosis complex, 6015 (41%) were positive by MGIT 960 TB system. In contrast, 3526 (24%) M. tuberculosis complex isolates grew on the conventional L.J medium. The mean turn around time for mycobacterial growth in smear-positive specimens was nine days for MGIT 960, and 38 days for L.J. medium whereas in smear negative specimens it was 16 days by MGIT vs. 48 days by L.J. CONCLUSION: MGIT 960 system with PNBA assay for identification of M. tuberculosis complex is a rapid and useful method in laboratories processing a large number of specimens.