Search

Food allergies affect millions of individuals worldwide, significantly impacting personal health and the economy. While avoiding allergenic foods remains the primary management strategy, consumers lack reliable means for immediate allergen detection in everyday dining settings. Here, we present iEAT2 (integrated Exogenous Allergen Test 2), an advanced electrochemical sensing system for rapid, on-site food allergen detection. Building upon our previous assay system, the iEAT2 features technical breakthroughs: i) a complete kit for sample processing, including a torsion device for food grinding, and ii) a new strategy for multi-electrode measurements, which enables the simultaneous detection of multiple allergens in a simplified electronic architecture. We designed a compact iEAT2 prototype capable of 16 electrochemical reactions. Experimental validation confirmed the independent electrochemical measurements in a simultaneous operation. Furthermore, the entire testing protocol was completed within 15 min, from allergen extraction to detection. The platform detected three common food allergens (gliadin, Ara h1, and ovalbumin) at concentrations below established allergic reaction thresholds. It also effectively identified cross-contamination events in real-world food samples. This technology may empower consumers to monitor food safety and improve its management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Globally, cervical cancer is the fourth leading cancer among women and is dominant in resource-poor settings in its occurrence and mortality. This study focuses on developing liquid immunogenic fiducial eluter (LIFE) Biomaterial with components that include biodegradable polymers, nanoparticles, and an immunoadjuvant. LIFE Biomaterial is designed to provide image guidance during radiotherapy similar to clinically used liquid fiducials while enhancing therapeutic efficacy for advanced cervical cancer. C57BL6 mice were used to grow subcutaneous tumors on bilateral flanks. The tumor on one flank was then treated using LIFE Biomaterial prepared with the immunoadjuvant anti-CD40, with/without radiotherapy at 6 Gy. Computed tomography (CT) and magnetic resonance (MR) imaging visibility were also evaluated in human cadavers. A pharmacodynamics study was also conducted to assess the safety of LIFE Biomaterial in healthy C57BL6 female mice. Results showed that LIFE Biomaterial could provide both CT and MR imaging contrast over time. Inhibition in tumor growth and prolonged significant survival (* p < 0.05) were consistently observed for groups treated with the combination of radiotherapy and LIFE Biomaterial, highlighting the potential for this strategy. Minimal toxicity was observed for healthy mice treated with LIFE Biomaterial with/without anti-CD40 in comparison to non-treated cohorts. The results demonstrate promise for the further development and clinical translation of this approach to enhance the survival and quality of life of patients with advanced cervical cancer.

The use of an immunogenic smart radiotherapy biomaterial (iSRB) for the delivery of anti-CD40 is effective in treating different cancers in animal models. This study further characterizes the use of iSRBs to evaluate any associated toxicity in healthy C57BL6 mice. iSRBs were fabricated using a poly-lactic-co-glycolic-acid (PLGA) polymer mixed with titanium dioxide (TiO 2 ) nanoparticles incorporated into its matrix. Animal studies included investigations of freely injected anti-CD40, anti-CD40-loaded iSRBs, unloaded iSRBs and control (healthy) animal cohorts. Mice were euthanized at pre-determined time points post-treatment to evaluate the serum chemistry pertaining to kidney and liver toxicity and cell blood count parameters, as well as pathology reports on organs of interest. Results showed comparable liver and kidney function in all cohorts. The results indicate that using iSRBs with or without anti-CD40 does not result in any significant toxicity compared to healthy untreated animals. The findings provide a useful reference for further studies aimed at optimizing the therapeutic efficacy and safety of iSRBs and further clinical translation work.

This technical note describes a stepwise osteotomy for zygomatic implant placement with an extra-sinus trajectory under navigation using virtual markers for registration. The stepwise osteotomy protocol divides the trajectory of the zygomatic implant osteotomy into three consecutive co-axial components. The aim is to achieve better control of the osteotomy under navigation and to minimize or eliminate any intermittent free-hand drilling. The stepwise osteotomy protocol facilitates the use of shorter drills to finish the zygomatic implant osteotomy at the entry location before switching back to the long drill to complete the whole osteotomy. This protocol has been applied in a patient and the preliminary result is promising. However, the clinical effectiveness of this approach requires further investigation in prospective clinical studies., Competing Interests: Competing interests None., (Copyright © 2023 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

New Jersey was among the first states impacted by the COVID-19 pandemic, with one of the highest overall death rates in the nation. Nevertheless, relatively few reports have been published focusing specifically on New Jersey. Here we report on molecular, clinical, and epidemiologic observations, from the largest healthcare network in the state, in a cohort of vaccinated and unvaccinated individuals with laboratory-confirmed SARS-CoV-2 infection. We conducted molecular surveillance of SARS-CoV-2-positive nasopharyngeal swabs collected in nine hospitals from December 2020 through June 2022, using both whole genome sequencing (WGS) and a real-time RT-PCR screening assay targeting spike protein mutations found in variants of concern (VOCs) within our region. De-identified clinical data were obtained retrospectively, including demographics, COVID-19 vaccination status, ICU admission, ventilator support, mortality, and medical history. Statistical analyses were performed to identify associations between SARS-CoV-2 variants, vaccination status, clinical outcomes, and medical risk factors. A total of 5007 SARS-CoV-2-positive nasopharyngeal swabs were successfully screened and/or sequenced. Variant screening identified three predominant VOCs, including Alpha ( n = 714), Delta ( n = 1877), and Omicron ( n = 1802). Omicron isolates were further sub-typed as BA.1 ( n = 899), BA.2 ( n = 853), or BA.4/BA.5 ( n = 50); the remaining 614 isolates were classified as "Other". Approximately 31.5% (1577/5007) of the samples were associated with vaccine breakthrough infections, which increased in frequency following the emergence of Delta and Omicron. Severe clinical outcomes included ICU admission (336/5007 = 6.7%), ventilator support (236/5007 = 4.7%), and mortality (430/5007 = 8.6%), with increasing age being the most significant contributor to each ( p < 0.001). Unvaccinated individuals accounted for 79.7% (268/336) of ICU admissions, 78.3% (185/236) of ventilator cases, and 74.4% (320/430) of deaths. Highly significant ( p < 0.001) increases in mortality were observed in individuals with cardiovascular disease, hypertension, cancer, diabetes, and hyperlipidemia, but not with obesity, thyroid disease, or respiratory disease. Significant differences ( p < 0.001) in clinical outcomes were also noted between SARS-CoV-2 variants, including Delta, Omicron BA.1, and Omicron BA.2. Vaccination was associated with significantly improved clinical outcomes in our study, despite an increase in breakthrough infections associated with waning immunity, greater antigenic variability, or both. Underlying comorbidities contributed significantly to mortality in both vaccinated and unvaccinated individuals, with increasing risk based on the total number of comorbidities. Real-time RT-PCR-based screening facilitated timely identification of predominant variants using a minimal number of spike protein mutations, with faster turnaround time and reduced cost compared to WGS. Continued evolution of SARS-CoV-2 variants will likely require ongoing surveillance for new VOCs, with real-time assessment of clinical impact.

Examining the neutralizing capacity of monoclonal antibodies (MAbs) used to treat COVID-19, as well as antibodies recovered from unvaccinated, previously vaccinated, and infected individuals, against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) remains critical to study. Here, we report on a SARS-CoV-2 nosocomial outbreak caused by the SARS-CoV-2 R.1 variant harboring the E484K mutation in a 281-bed psychiatric facility in New Jersey among unvaccinated inpatients and health care professionals (HCPs). A total of 81 inpatients and HCPs tested positive for SARS-Cov-2 by reverse transcription (RT)-PCR from 29 October 9 to 30 November 2020. The R.1 variant exhibits partial or complete resistance to two MAbs in clinical use, as well as 2 receptor binding domain MAbs and 4 N-terminal domain (NTD) MAbs. NTD MAbs against pseudovirus harboring single characteristic R.1 mutations highlight the role of S255F in loss of activity. Additionally, we note dampened neutralization capacity by plasma from individuals with previous SARS-CoV-2 infection or sera from vaccinated individuals. The relative resistance of the R.1 variant is likely lower than that of B.1.351 and closer to that of P.1 and B.1.526. The R.1 lineage has been reported in 47 states in the United States and 40 countries. Although high proportions exhibited symptoms (26% and 61% among patients and HCPs, respectively) and relative antibody resistance, we detected only 10 R.1 variants from over 2,900 samples (~0.34%) collected from January to October 2021. Among 3 vaccinated individuals previously infected with R.1, we observed robust neutralizing antibody responses against SARS-CoV-2 wild type and VOCs. IMPORTANCE The neutralizing capacities of monoclonal antibodies used to treat COVID-19 and of those recovered from previously infected and vaccinated individuals against SARS-CoV-2 variants of concern (VOCs) remain important questions. We report on a nosocomial outbreak caused by a SARS-CoV-2 R.1 variant harboring an E484K mutation among 81 unvaccinated inpatients and health care professionals. We note high attack rates with symptoms in nearly 50% of infected individuals, in sharp contrast to an unrelated institutional outbreak caused by the R.1 variant among a vaccinated population. We found little evidence of significant community spillover. This variant exhibits partial or complete resistance to two monoclonal antibodies in clinical use and dampened the neutralization capacity of convalescent-phase plasma from individuals with previous infection or sera from vaccinated individuals. Among three vaccinated individuals previously infected with R.1, we observed robust neutralizing antibody responses against SARS-CoV-2 wild type and VOCs. These findings underscore the importance of vaccination for prevention of symptomatic COVID-19 disease.

Emergence of SARS-CoV-2 with high transmission and immune evasion potential, the so-called variants of concern (VOC), is a major concern. We describe the early genomic epidemiology of SARS-CoV-2 recovered from vaccinated health care professionals (HCP). Our postvaccination COVID-19 symptoms-based surveillance program among HCPs in a 17-hospital network identified all vaccinated HCPs who tested positive for COVID-19 after routine screening or after self-reporting. From 1 January 2021 to 30 April 2021, 23,687 HCPs received either mRNA-1273 or BNT162b2 mRNA vaccine. All available postvaccination SARS-CoV-2 samples and a random collection from nonvaccinated patients during the similar time frame were subjected to VOC screening and whole-genome sequencing (WGS). Sixty-two percent (23,697/37,500) of HCPs received at least one vaccine dose, with 60% (22,458) fully vaccinated. We detected 138 (0.58%, 138/23,697) COVID-19 cases, 105 among partially vaccinated and 33 (0.15%, 33/22,458) among fully vaccinated. Five partially vaccinated required hospitalization, four with supplemental oxygen. VOC screening from 16 fully vaccinated HCPs identified 6 (38%) harboring N501Y and 1 (6%) with E484K polymorphisms; percentage of concurrent nonvaccinated samples was 37% (523/1,404) and 20% (284/1,394), respectively. There was an upward trend from January to April for E484K/Q (3% to 26%) and N501Y (1% to 49%). WGS analysis from vaccinated and nonvaccinated individuals indicated highly congruent phylogenies. We did not detect an increased frequency of any receptor-binding domain (RBD)/N-terminal domain (NTD) polymorphism between groups ( P  > 0.05). Our results support robust protection by vaccination, particularly among recipients of both doses. Despite VOCs accounting for over 40% of SARS-CoV-2 from fully vaccinated individuals, the genomic diversity appears to proportionally represent VOCs among nonvaccinated populations. IMPORTANCE A number of highly effective vaccines have been developed and deployed to combat the COVID-19 pandemic. The emergence and epidemiological dominance of SARS-CoV-2 mutants with high transmission potential and immune evasion properties, the so-called variants of concern (VOC), continue to be a major concern. Whether these VOCs alter the efficacy of the administered vaccines is of great concern and a critical question to study. We describe the initial genomic epidemiology of SARS-CoV-2 recovered from partial/fully vaccinated health care professionals and probe specifically for VOC enrichment. Our findings support the high level of protection provided by full vaccination despite a steep increase in the prevalence of polymorphisms associated with increased transmission potential (N501Y) and immune evasion (E484K) in the nonvaccinated population. Thus, we do not find evidence of VOC enrichment among vaccinated groups. Overall, the genomic diversity of SARS-CoV-2 recovered postvaccination appears to proportionally represent the observed viral diversity within the community.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs), harboring spike protein N-terminal domain (NTD) or receptor-binding domain (RBD) mutations, exhibit reduced in vitro susceptibility to convalescent-phase serum, commercial antibody cocktails, and vaccine neutralization and have been associated with reinfections. The accumulation of these mutations could be the consequence of intrahost viral evolution due to prolonged infection in immunocompromised hosts. In this study, we document the microevolution of SARS-CoV-2 recovered from sequential tracheal aspirates from an immunosuppressed patient on steroids and convalescent plasma therapy and identify the emergence of multiple NTD and RBD mutations. SARS-CoV-2 genomes from the first swab (day 0) and from three tracheal aspirates (days 7, 21, and 27) were compared at the sequence level. We identified a mixed viral population with five different S protein mutations (141 to 144 deletion, 243 to 244 deletion, E484K, Q493K, and Q493R) at the NTD or RBD region from the second tracheal aspirate sample (day 21) and a predominance of the S protein 141 to 144 LGVY deletion and E484K mutant on day 27. The neutralizing antibodies against various S protein lentiviral pseudovirus mutants, as well as the anti-SARS-CoV-2 total Ig and IgG, showed "U" shape dynamics, in support of the endogenous development of neutralizing antibodies. The patient's compromised immune status, the antirejection regiment, convalescent plasma treatment, and the development of neutralizing antibodies may have resulted in unique selective pressures on the intrahost genomic evolution, and this observation supports the hypotheses that VOCs can independently arise and that immunocompromised patients on convalescent plasma therapy are potential breeding grounds for immune escape mutants. IMPORTANCE Over a year of the COVID-19 pandemic, distinct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages have arisen in multiple geographic areas around the world. SARS-CoV-2 variants of concern (VOCs), i.e., B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), and B.1.617.2 (delta), harboring mutations and/or deletions in spike protein N-terminal domain (NTD) or receptor-binding domain (RBD) regions showed evidence of increased transmissibility and disease severity and possible reduced vaccine efficacy. In this study, we report the emergence of five different NTD and RBD mutations in an uncommon SARS-CoV-2 B.1.369 lineage from an immunosuppressed patient undergoing steroid and convalescent plasma therapy. The observation highlighted that VOCs can independently arise in immunocompromised populations undergoing anti-SARS-CoV-2 therapy, and enhanced measures will be required to reduce the transmission.

Fungal infections are common complications of respiratory viral infections and are associated with the increased need for intensive care and elevated mortality. Data regarding microbiological and molecular characteristics of such infections in COVID-19 patients are scarce. Here, we performed a comprehensive analysis, including species identification, antifungal susceptibility testing, molecular resistance determinants analysis, typing, and retrospective clinical data review, of fungal isolates recovered from 19 COVID-19 patients, who were hospitalized at the Hackensack University Medical Center (HUMC) in Hackensack, New Jersey, USA, in the initial phase of the pandemic from April-May 2020. In total, 17 Candida albicans , two C. parapsilosis , and two Aspergillus fumigatus were analyzed. All Candida spp. isolates were susceptible to micafungin and azole drugs (fluconazole, voriconazole, posaconazole, itraconazole, isavuconazole). A. fumigatus isolates were susceptible to micafungin and all triazole drugs except fluconazole (intrinsic resistance). Multilocus sequence typing (MLST) of C. albicans isolates revealed 15 different sequence types (STs), which clustered below the clade-defining limit of p-distance < 0.04. Pulsed-field gel electrophoresis (PFGE) karyotyping revealed no chromosomal rearrangements in these isolates. A. fumigatus isolates were of different, non-related genotypes. We speculate that virus- and drug-induced immunosuppression (94.7% of the patients received corticosteroids), together with prolonged hospital stay (median duration of 29 days) and mechanical ventilation (median duration of 24 days) likely increased the susceptibility to secondary respiratory and bloodstream infections in the studied patient population. The presence of fungi in blood or respiratory tract fluid was a prognosticator for poor clinical outcome, which presented as an 89.5% 30-day mortality in our patient cohort.

New Jersey was an early epicenter for the COVID-19 pandemic in the United States, yet information on hospitalized COVID-19 patients from this area is scarce. This study aimed to provide data on demographics and clinical features of a hospitalized patient population who were confirmed with infection by our in-house (CDI) real-time reverse-transcription polymerase chain reaction (RT-PCR) test. We included consecutive patients who were admitted to Hackensack Meridian Health system hospitals with laboratory-confirmed diagnoses of COVID-19 at Hackensack University Medical Center by the CDI virus test between March 12, 2020, and April 8, 2020. Clinical data and viral testing results were collected and analyzed for characteristics associated with outcomes, as well as the correlation with viral load. A total of 722 patients were included in the study, with a median age of 63 (interquartile range (IQR), 51-75) and 272 (37.7%) females. Mortality of this case series was 25.8%, with a statistically significant linear increase observed from age 40 to ≥ 80 by 10-year intervals. Viral load, as indicated by the cycle of threshold (Ct) values from the RT-PCR test, was significantly higher in the oldest patient group (≥ 80), and inversely correlated with survival. This is the first report to describe the clinical characteristics and outcomes in a large hospitalized COVID-19 patient series from New Jersey. Findings from this study are valuable to the ongoing response of both nationwide healthcare networks and the medical research community.

Polyaniline (PANI) is one of the most studied conducting polymers owing to its high electrical conductivity, straightforward synthesis and stability. Graphene-supported PANI nanocomposite materials combine the superior physical properties of graphene, synergistically enhancing the performance of PANI as well as giving rise to new properties. Covalent nanocomposites have shown to give higher stability and better performance than their non-covalent counterparts, however, the covalent graphene-PANI nanocomposite are primarily prepared from graphene oxide. We report a new method to synthesize covalent graphene-PANI nanocomposites from pristine graphene. Using few-layer graphene (FLG) flakes as the model system, we first conjugated aniline to FLG via a perfluorophenyl azide (PFPA)-mediated coupling chemistry. A subsequent in situ polymerization of aniline gave polyaniline covalently grafted on the FLG surface. Characterization by FTIR, TEM, SEM, XPS, XRD and electrochemistry confirmed the successful conjugation of PANI to FLG. The grafting density of PANI was estimated by thermal analysis to be ∼26%. As the PFPA-mediated coupling chemistry is applicable to other carbon materials including carbon nanotubes and fullerene, the method developed in this work can be readily adapted to grow PANI on these materials., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

This article describes an electrochemical method to remove bacterial biofilm from a stainless steel (SS) surface using a potential pulse/reverse pulse technique. This technique employs a periodic waveform that consists of anodic and cathodic pulses. The pulses can effectively strip a thin layer of metal off the SS surface, along with the adherent biofilm, in a saline solution. Not only can the pulses effectively remove biofilm from the SS surface, but they also regenerate the original mirror-like shiny surface. The importance of this electrochemical biofilm removal method is its wide applicability for any types of biofilms. That is, instead of directly removing the biofilm, it removes a very thin layer of the metal under the biofilm. Thus, the removal process is independent to the nature of the biofilms. Furthermore, this electrochemical biofilm removal method is rapid (less than 30 s of potential pulse time) and does not require hazardous chemicals.

In this study, we investigate the use of multifunctional smart radiotherapy biomaterials (SRBs) loaded with immunoadjuvants for boosting the abscopal effect of local radiotherapy (RT). SRBs were designed similar to currently used inert RT biomaterials, incorporating a biodegradable polymer with reservoir for loading payloads of the immunoadjuvant anti-CD40 monoclonal antibody. Lung (LLC1) tumors were generated both on the right and left flank of each mouse, with the left tumor representing metastasis. The mice were randomized and divided into eight cohorts with four cohorts receiving image-guided RT (IGRT) at 5 Gy and another similar four cohorts at 0 Gy. IGRT and Computed Tomography (CT) imaging were performed using a small animal radiation research platform (SARRP). Tumor volume measurements for both flank tumors and animal survival was assessed over 25 weeks. Tumor volume measurements showed significantly enhanced inhibition in growth for the right flank tumors of mice in the cohort treated with SRBs loaded with CD40 mAbs and IGRT. Results also suggest that the use of polymeric SRBs with CD40 mAbs without RT could generate an immune response, consistent with previous studies showing such response when using anti-CD40. Overall, 60% of mice treated with SRBs showed complete tumor regression during the observation period, compared to 10% for cohorts administered with anti-CD40 mAbs, but no SRB. Complete tumor regression was not observed in any other cohorts. The findings justify more studies varying RT doses and quantifying the immune-cell populations involved when using SRBs. Such SRBs could be developed to replace currently used RT biomaterials, allowing not only for geometric accuracy during RT, but also for extending RT to the treatment of metastatic lesions.

Stomatologists and dental practitioners, as they are called in different parts of the world according to tradition and history, are basically physicians who specialise in the study and treatment of diseases of the mouth and surrounding structures. They have always been outstanding in advocating the reduction of sugar consumption, mainly due to its direct connection to the pathogenesis of dental caries. Increasingly, it has come to the attention of researchers, epidemiologists and many healthcare workers and professionals that excessive consumption of sugar is also closely tied to the increase in tandem of our current major health issues like obesity, diabetes, heart, liver and kidney disease, and a host of other associated ailments. This development of current health crises throughout the world wherever traditional diets are replaced with modern fast food diets, which are usually packed with hidden, added refined sugars, is extremely troubling. It becomes all the more urgent and incumbent upon clinicians and stomatologists throughout the world to redouble their efforts to reduce and even eliminate the excessive consumption of added or extrinsic or secondary or hidden sugars to food and drinks. It will not only be to reduce dental caries, but also to reduce the many systemic and organ diseases associated with added sugars and which also exacerbate many oral diseases. This review is to give a basic history of sugar, the current understanding of sugar metabolism and the developing literature and research on the impact of sugar consumption on oral and overall health, as the mouth cannot be divorced from the body and vice versa. The author hopes to kick-start more research into this area that will result in various positive developments in the food and drink industry and persuade stakeholders to comprehensively address this universal health crisis that is closely tied to excessive consumption of added sugar in all its forms.

In this Article, we report a coulometric sensing platform that is capable of sensing analytes on a working electrode and providing a visual readout of the analyte concentration on a silver (Ag) band counter electrode in a microchannel. The display mechanism relies on the electro-oxidation of metallic Ag as a complementary reaction to the sensing reduction reaction. The Ag band counter electrode is arranged longitudinally in a microchannel while the frontal tip of the band electrode directly faces a gold (Au) working electrode, which lies across the microchannel. The Ag oxidation always occurs at the band electrode's tip region that faces the working electrode due to the Ohmic potential drop across the solution in the microchannel. The decrement of the Ag electrode, which is clearly measurable with the naked eye, correlates linearly with an analyte concentration (e.g., 0.1-2.5 mM p-benzoquinone) and with an analyte feeding rate (i.e., a sample solution flow rate of 1.0-75.0 μL min(-1)). The platform design is also effective for a model analyte of horseradish peroxidase (HRP)-avidin in the dynamic range of 0.1-3.0 μg mL(-1).

Fludarabine, cyclophosphamide, and rituximab (FCR) remains the standard of care for fit chronic lymphocytic leukemia (CLL) patients requiring first therapy. However, side effects can be significant, and patients with poor risk features have inferior outcomes. The purpose of this study was to evaluate reduced-dose FCR (FCR-Lite) plus lenalidomide (FCR(2) ) followed by lenalidomide maintenance as a strategy to shorten immunochemotherapy in untreated CLL. Patients received four to six cycles of FCR(2) . Patients who were minimal residual disease (MRD) negative in peripheral blood (PB) and bone marrow (BM) initiated 12 months of lenalidomide maintenance after either four or six cycles (based on MRD status). The primary study endpoint was the complete response (CR) rate after four cycles of FCR(2) . Twenty patients were evaluable. After four cycles of FCR(2) , response rates were: CR, 45.0%; CR with incomplete blood count recovery (CRi), 5.0%; partial response (PR), 45.0%; and stable disease (SD), 5.0%. BM and PB samples from 27.8% and 52.9% of patients, respectively, were MRD negative. After six cycles, response rates were: CR, 58.3%; CRi, 16.7%; and PR, 25.0%. BM and PB samples from 50.0% and 72.7% of patients, respectively, were MRD negative. Overall, 75% of evaluable patients achieved a CR or CRi following FCR(2) . After 17.4 months of median follow-up, one progression and one death occurred. Our findings suggest that FCR(2) combines encouraging clinical activity with acceptable toxicity in previously untreated CLL. Lenalidomide can be safely added to FCR and may reduce chemotherapy exposure without compromising outcomes., (© 2015 Wiley Periodicals, Inc.)

Lymphocytic neoplasm involving the heart is not common and usually presents with pericardial effusion or focal myocardial infiltration. Myocardial infarctions due to leukemic infiltration of the coronary arteries are rarely reported. We present the case of a 52-year-old Guatemalan man with a one-year history of untreated T-cell prolymphocytic leukemia. He was admitted to our hospital for chemotherapy and evaluation of a pulmonary cavitary lesion by wedge resection. During sedation, the patient experienced acute respiratory failure and hypovolemic shock, from which he could not be resuscitated. Autopsy revealed that leukemic cells extensively infiltrated the aorta, myocardium, and coronary arteries. The lumina of the 3 major coronary artery branches showed 70% to 95% stenosis, with multifocal remote myocardial infarctions. Tumor cells were also detected in the lungs and other organs. The acute cardiorespiratory insufficiency secondary to leukemia-particularly the extensive infiltration of the coronary arteries and myocardium, and the multiple myocardial infarctions-eventually resulted in cardiac death.

Relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is associated with a poor prognosis. Outcomes are particularly poor following immunochemotherapy failure or relapse within 12 months of induction. We conducted a Phase I/II trial of lenalidomide plus RICE (rituximab, ifosfamide, carboplatin, and etoposide) (RICER) as a salvage regimen for first-relapse or primary refractory DLBCL. Dose-escalated lenalidomide was combined with RICE every 14 d. After three cycles of RICER, patients with chemosensitive disease underwent stem cell collection and consolidation with BEAM [BCNU (carmustine), etoposide, cytarabine, melphalan] followed by autologous stem cell transplantation (autoSCT). Patients who recovered from autoSCT toxicities within 90 d initiated maintenance treatment with lenalidomide 25 mg daily for 21 d every 28 d for 12 months. No dose-limiting or unexpected toxicities occurred with lenalidomide 25 mg plus RICE. Grade 3/4 haematological toxicities resolved appropriately, and planned dose density and dose intensity of RICER were preserved. No lenalidomide or RICE dose reductions were required in any of the three cycles. After two cycles of RICER, nine of 15 patients (60%) achieved a complete response, and two achieved a partial response (13%). Combining lenalidomide with RICE is feasible, and results in promising response rates (particularly complete response rates) in high-risk DLBCL patients., (© 2014 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.)

The electronic conductivity of films of iridium oxide (IrO(x)) composed of ca. 2 nm nanoparticles (NPs) is strongly dependent on the film oxidation state. The Ir(IV)O(x) NPs can be electrochemically converted to several oxidation states, ranging from Ir(III) to Ir(V) oxides. The NP films exhibit a very high apparent conductivity, e.g., 10(-2) S cm(-1), when the NPs are in the oxidized +4/+5 state. When the film is fully reduced to its Ir(III) state, the apparent conductivity falls to 10(-6) S cm(-1).

The increasing occurrence of food frauds suggests that species identification should be part of food authentication. Current molecular-based species identification methods have their own limitations or drawbacks, such as relatively time-consuming experimental steps, expensive equipment and, in particular, these methods cannot identify mixed species in a single experiment. This project proposes an improved method involving PCR amplification of the COI gene and detection of species-specific sequences by hybridisation. Major innovative breakthrough lies in the detection of multiple species, including pork, beef, lamb, horse, cat, dog and mouse, from a mixed sample within a single experiment. The probes used are species-specific either in sole or mixed species samples. As little as 5 pg of DNA template in the PCR is detectable in the proposed method. By designing species-specific probes and adopting reverse dot blot hybridisation and flow-through hybridisation, a low-cost high-density DNA-based multi-detection test suitable for routine inspection of meat species was developed., (© 2013.)

Subtypes of diffuse large B-cell lymphoma (DLBCL) that have inferior outcomes after front-line therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) have been identified. While it is agreed that R-CHOP is probably not adequate in these patients, there is no standard treatment approach for patients with DLBCL with high-risk features. We present results of a retrospective cohort study of high-risk DLBCL (defined as having at least one unfavorable risk factor: non-germinal center [GC] subtype by immunohistochemistry [IHC], Ki-67 ≥ 80%, high International Prognostic Index [IPI], c-MYC rearrangement) treated with R-HCVAD/R-MTX-AraC (rituximab, cyclophosphamide-fractionated, vincristine, doxorubicin and dexamethasone alternating with rituximab, methotrexate and cytarabine; R-HCVAD) as front-line therapy. With a median follow-up of 25.3 months, the 3-year PFS and OS estimates are 79% (95% confidence interval [CI], 65-88%) and 76% (95% CI, 61-86%), respectively, which are higher than those for historical comparisons with R-CHOP data for high-risk patients. These data are in accord with other recent reports of dose-intense front-line therapy of high-risk DLBCL. This analysis represents the largest reported cohort of patients with DLBCL treated with R-HCVAD. These data suggest that R-HCVAD can overcome traditional poor risk features such as high IPI, high Ki-67 and non-GC IHC pattern. Future work will focus on identifying molecular markers for failure in patients with DLBCL treated with dose-intensive regimens.

We report a two-channel microelectrochemical sensor that communicates between separate sensing and reporting microchannels via one or more bipolar electrodes (BPEs). Depending on the contents of each microchannel and the voltage applied across the BPE, faradaic reactions may be activated simultaneously in both channels. As presently configured, one end of the BPE is designated as the sensing pole and the other as the reporting pole. When the sensing pole is activated by a target, electrogenerated chemiluminescence (ECL) is emitted at the reporting pole. Compared to previously reported single-channel BPE sensors, the key advantage of the multichannel architecture reported here is physical separation of the ECL reporting cocktail and the solution containing the target. This prevents chemical interference between the two channels.

An infiltrate mimicking subcutaneous panniculitis associated with a granulomatous response represents an uncommon histopathologic presentation of lymphoma. We report three cases, comprising one case each of nasal-type extranodal NK/T-cell lymphoma, cutaneous γ/δ T-cell lymphoma and human T-lymphotropic virus-I associated adult T-cell leukemia/lymphoma, which based on initial histopathologic and/or clinical presentation were thought to represent systemic lupus erythematosus, sarcoidosis and psoriasiform dermatitis, respectively. Excisional biopsies of indurated lesions performed at our institute; however, in each case showed an atypical subcutaneous lymphohistiocytic infiltrate associated with a variable number of granulomas. Extensive immunophenotypic characterization, in conjunction with histomorphologic and molecular analysis, established the diagnosis of lymphoma in all instances. All patients had a rapidly progressive clinical course and death was attributable to complications of lymphoma shortly after diagnosis. These cases highlight the importance of using a multimodality diagnostic approach to distinguish lymphomas masquerading as granulomatous panniculitis from inflammatory or reactive disorders associated with such histopathologic patterns., (Copyright © 2011 John Wiley & Sons A/S.)

Past studies have shown decreased hematogones in the bone marrow of patients with myelodysplastic syndromes and acquired aplastic anemia. In this study, we examined the bone marrow of patients with chronic myeloid leukemia (n = 33, mean age 49 years, age range 2-83 years) for the presence of hematogones and compared their frequency with that of age-matched controls (n = 50). We found that the percentages of total and stage I hematogones were decreased in chronic myeloid leukemia at diagnosis (n = 25) and at follow-up post therapy (n = 8) when compared to age-matched controls (diagnosis, total: 0.29% vs. 0.87%, p = 0.001; diagnosis, stage I: 0.06% vs. 0.20%, p = 0.008; follow-up, total: 0.17% vs. 0.87%, p < 0.001; follow-up, stage I: 0.04 vs. 0.20, p = 0.003). We also found a significant decrease in the number of natural killer cells in patients with chronic myeloid leukemia at diagnosis. Further studies are warranted to elucidate the mechanism of hematogone decrease in chronic myeloid leukemia and whether this finding also applies to other myeloproliferative neoplasms.

Here we report a simple design philosophy, based on the principles of bipolar electrochemistry, for the operation of microelectrochemical integrated circuits. The inputs for these systems are simple voltage sources, but because they do not require much power they could be activated by chemical or biological reactions. Device output is an optical signal arising from electrogenerated chemiluminescence. Individual microelectrochemical logic gates are described first, and then multiple logic circuits are integrated into a single microfluidic channel to yield an integrated circuit that can perform parallel logic functions. AND, OR, NOR, and NAND gates are described. Eventually, systems such as those described here could provide on-chip data processing functions for lab-on-a-chip devices.

Over the past decade, bipolar electrochemistry has emerged from relative obscurity to provide a promising new means for integrating electrochemistry into lab-on-a-chip systems. This article describes the fundamental operating principles of bipolar electrodes, as well as several interesting applications.

Here we report a new type of sensing platform that is based on electrodissolution of a metallic bipolar electrode (BPE). When the target DNA binds to the capture probe at the cathodic pole of the BPE, it triggers the oxidation and dissolution of Ag metal present at the anodic pole. The loss of Ag is easily detectable with the naked eye or a magnifying glass and provides a permanent record of the electrochemical history of the electrode. More importantly, the decrease in the length of the BPE can be directly correlated to the number of electrons passing through the BPE and hence to the sensing reaction at the cathode.

In this paper, we report a new electroanalytical technique we call snapshot voltammetry. This method combines the properties of bipolar electrodes with electrogenerated chemiluminescence (ECL) to provide a means for recording optical voltammograms in a single micrograph. In essence, the information in a snapshot voltammogram is contained in the spatial domain rather than in the time domain, which is the case for conventional voltammetry. The use of a triangle-shaped bipolar electrode stabilizes the interfacial potential difference along its length. Basic electrochemical parameters extracted from snapshot voltammograms are in good agreement with those obtained by conventional voltammetry. Although not explicitly demonstrated in this paper, this method offers the possibility of using arrays of bipolar electrodes to obtain numerous snapshot voltammograms simultaneously.

We report a microelectrochemical array composed of 1000 individual bipolar electrodes that are controlled with just two driving electrodes and a simple power supply. The system is configured so that faradaic processes occurring at the cathode end of each electrode are correlated to light emission via electrogenerated chemiluminescence (ECL) at the anode end. This makes it possible to read out the state of each electrode simultaneously. The significant advance is that the electrode array is fabricated on a glass microscope slide and is operated in a simple electrochemical cell. This eliminates the need for microfluidic channels, provides a fabrication route to arbitrarily large electrode arrays, and will make it possible to place sensing chemistries onto each electrode using a robotic spotter.

We report an electrochemical DNA microarray sensor whose function is controlled with just two wires regardless of the number of individual sensing electrodes. The bipolar sensing electrode is modified with probe DNA, and the anode end of each electrode is configured to emit light (electrogenerated chemiluminescence) upon hybridization of cDNA labeled with electrocatalytic (oxygen reduction) Pt nanoparticles at the cathode. The important finding is that DNA can be selectively detected at an array of three electrodes. In principle, however, this advance provides a means for controlling the potential of many electrodes using just two wires and then indirectly determining the current flowing through all of them simultaneously by correlating light emission to current.

Purpose: Changes in referral patterns and resource allocation into Centers of Excellence affect the educational experience of urology trainees by altering resident exposure to patients and clinicians, especially at sites where subspecialty deficiencies exist. Access to educators at Centers of Excellence using interactive videoconferencing technology may facilitate residency training objectives and enhance trainees' overall educational experience. We prospectively evaluated the implementation of this technology at tertiary care teaching centers to enhance urology resident education., Materials and Methods: Using videoconferencing technology, urology residents at the University of Western Ontario (London, Canada) participated in a series of didactic, interactive pediatric urology teleteaching seminars. These were presented by an expert pediatric urologist from the Hospital for Sick Children, Toronto, Canada. Using a 5-point Likert scale (1-strongly disagree, 5-strongly agree), participants responded to statements pertaining to seminar content, technology and ease of use at the completion of each session. The results were subsequently tabulated and evaluated to determine the effectiveness and accessibility of the program in providing expert pediatric urological education to residents at a remote urology training program., Results: The entire urology resident staff from postgraduate year 1 to 5 participated in the seminar program. The overall acceptance of this medium was high (mean score 4.5). The quality of presentation, as well as picture and sound quality, all received mean scores greater than 4. Participants indicated that their ability to interact with the presenter was not inhibited by using this medium. All participants agreed that they would use this technology in the future (mean score 4.5) and that the presentation would not be improved if the presenter were on-site. Due to preexisting technology at both centers, no direct cost was incurred throughout the study., Conclusions: Our experience suggests that interactive teleteaching using readily available, existing technology, is a cost-effective and accepted method of providing trainees with an appropriate educational experience. In centers where subspecialty deficiencies exist, this medium may provide residents with the necessary education requirements of their respective programs without the need for costly teacher (or student) travel. Continual improvements in technology as well as the addition of multiple sites will increased this medium's impact in the future.