Efficacy of ceftazidime-avibactam in solid organ transplant recipients with bloodstream infections caused by carbapenemase-producing Klebsiella pneumoniae.

We aimed to compare the efficacy of ceftazidime-avibactam (CAZ-AVI) versus the best available therapy (BAT) in solid organ transplant (SOT) recipients with bloodstream infection caused by carbapenemase-producing Klebsiella pneumoniae (CPKP-BSI). A retrospective (2016-2021) observational cohort study was performed in 14 INCREMENT-SOT centers (ClinicalTrials.gov identifier: NCT02852902; Impact of Specific Antimicrobials and MIC Values on the Outcome of Bloodstream Infections Due to ESBL- or Carbapenemase-producing Enterobacterales in Solid Organ Transplantation: an Observational Multinational Study). Outcomes were 14-day and 30-day clinical success (complete resolution of attributable manifestations, adequate source control, and negative follow-up blood cultures) and 30-day all-cause mortality. Multivariable logistic and Cox regression analyses adjusted for the propensity score to receive CAZ-AVI were constructed. Among 210 SOT recipients with CPKP-BSI, 149 received active primary therapy with CAZ-AVI (66/149) or BAT (83/149). Patients treated with CAZ-AVI had higher 14-day (80.7% vs 60.6%, P = .011) and 30-day (83.1% vs 60.6%, P = .004) clinical success and lower 30-day mortality (13.25% vs 27.3%, P = .053) than those receiving BAT. In the adjusted analysis, CAZ-AVI increased the probability of 14-day (adjusted odds ratio [aOR], 2.65; 95% confidence interval [CI], 1.03-6.84; P = .044) and 30-day clinical success (aOR, 3.14; 95% CI, 1.17-8.40; P = .023). In contrast, CAZ-AVI therapy was not independently associated with 30-day mortality. In the CAZ-AVI group, combination therapy was not associated with better outcomes. In conclusion, CAZ-AVI may be considered a first-line treatment in SOT recipients with CPKP-BSI.

Fabrication of sandwich structures of Ag/analyte/MoO3sea urchins for SERS detection of methylene blue dye molecules.

A substrate for surface-enhanced Raman spectroscopy (SERS) in a sandwich configuration, noble metal/analyte/defect-rich metal oxide, is demonstrated for the detection of methylene blue(MB). The sandwich structure (Ag/MB/SUMoO3) is fabricated by physical vapour deposition of Ag nanoparticles over the MB analytes that are adsorbed on sea urchin MoO3(SUMoO3). SUMoO3are grown on a glass substrate by chemical bath deposition. The morphology of the fabricated sandwich structures shows serrated spikes of MoO3from the core region decorated with strings of silver nanoparticles. The silver-decoration and the oxygen defects of SUMoO3promote absorption in the visible region and facilitate charge transfer between MB and SUMoO3, which are beneficial for achieving superior SERS properties in this configuration compared to the contribution from individual components alone. The sandwich structure is able to detect the MB molecule up to 100 nM with an enhancement factor of 8.1 × 106. The relative standard deviation of SERS intensity for the 1618 cm-1peak of MB across the substrate is 29.2%. The configuration offers stability to SERS substrate under ambient conditions. The combined effect of charge transfer, surface plasmon resonance, and MB resonance results in the improved SERS detection of MB molecules with the Ag/MB/SUMoO3sandwich structure.

National Landscape of Human Immunodeficiency Virus-Positive Deceased Organ Donors in the United States.

BACKGROUND: Organ transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV-positive donors is critical for safety. METHODS: We performed a prospective study of donors with HIV-positive and HIV false-positive (FP) test results within the HIV Organ Policy Equity (HOPE) Act in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262, NCT03500315, and NCT03734393). We compared clinical characteristics in HIV-positive versus FP donors. We measured CD4 T cells, HIV viral load (VL), drug resistance mutations (DRMs), coreceptor tropism, and serum antiretroviral therapy (ART) detection, using mass spectrometry in HIV-positive donors. RESULTS: Between March 2016 and March 2020, 92 donors (58 HIV positive, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidneys and 46 livers). Each year the number of donors increased. The prevalence of hepatitis B (16% vs 0%), syphilis (16% vs 0%), and cytomegalovirus (CMV; 91% vs 58%) was higher in HIV-positive versus FP donors; the prevalences of hepatitis C viremia were similar (2% vs 6%). Most HIV-positive donors (71%) had a known HIV diagnosis, of whom 90% were prescribed ART and 68% had a VL <400 copies/mL. The median CD4 T-cell count (interquartile range) was 194/µL (77-331/µL), and the median CD4 T-cell percentage was 27.0% (16.8%-36.1%). Major HIV DRMs were detected in 42%, including nonnucleoside reverse-transcriptase inhibitors (33%), integrase strand transfer inhibitors (4%), and multiclass (13%). Serum ART was detected in 46% and matched ART by history. CONCLUSION: The use of HIV-positive donor organs is increasing. HIV DRMs are common, yet resistance that would compromise integrase strand transfer inhibitor-based regimens is rare, which is reassuring regarding safety.

HOPE in action: A prospective multicenter pilot study of liver transplantation from donors with HIV to recipients with HIV.

Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D-/R+) LT. We quantified patient survival, graft survival, rejection, serious adverse events (SAEs), human immunodeficiency virus (HIV) breakthrough, infections, and malignancies, using Cox and negative binomial regression with inverse probability of treatment weighting. Between March 2016-July 2019, there were 45 LTs (8 simultaneous liver-kidney) at 9 centers: 24 HIV D+/R+, 21 HIV D-/R+ (10 D- were false-positive). The median follow-up time was 23 months. Median recipient CD4 was 287 cells/µL with 100% on antiretroviral therapy; 56% were hepatitis C virus (HCV)-seropositive, 13% HCV-viremic. Weighted 1-year survival was 83.3% versus 100.0% in D+ versus D- groups (p = .04). There were no differences in one-year graft survival (96.0% vs. 100.0%), rejection (10.8% vs. 18.2%), HIV breakthrough (8% vs. 10%), or SAEs (all p > .05). HIV D+/R+ had more opportunistic infections, infectious hospitalizations, and cancer. In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation.

Coronavirus Disease 2019 in Solid Organ Transplant: A Multicenter Cohort Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well described. METHODS: We performed a multicenter cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients. RESULTS: Four hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (interquartile range [IQR] 46-57), median time post-transplant was 5 years (IQR 2-10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 [78%]), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 [adjusted odds ratio [aOR] 3.0, 95% confidence interval [CI] 1.7-5.5, P < .001], congestive heart failure [aOR 3.2, 95% CI 1.4-7.0, P = .004], chronic lung disease [aOR 2.5, 95% CI 1.2-5.2, P = .018], obesity [aOR 1.9, 95% CI 1.0-3.4, P = .039]) and presenting findings (lymphopenia [aOR 1.9, 95% CI 1.1-3.5, P = .033], abnormal chest imaging [aOR 2.9, 95% CI 1.1-7.5, P = .027]) were independently associated with mortality. Multiple measures of immunosuppression intensity were not associated with mortality. CONCLUSIONS: Mortality among SOT recipients hospitalized for COVID-19 was 20.5%. Age and underlying comorbidities rather than immunosuppression intensity-related measures were major drivers of mortality.

SARS-CoV-2 Infections among Recent Organ Recipients, March-May 2020, United States.

We conducted public health investigations of 8 organ transplant recipients who tested positive for severe acute respiratory syndrome coronavirus 2 infection. Findings suggest the most likely source of transmission was community or healthcare exposure, not the organ donor. Transplant centers should educate transplant candidates and recipients about infection prevention recommendations.

Propensity Score and Desirability of Outcome Ranking Analysis of Ertapenem for Treatment of Nonsevere Bacteremic Urinary Tract Infections Due to Extended-Spectrum-Beta-Lactamase-Producing Enterobacterales in Kidney Transplant Recipients.

There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.

Isavuconazole for the prophylaxis and treatment of invasive fungal disease: A single-center experience.

BACKGROUND: Invasive fungal disease (IFD) is a serious complication among the immunocompromised population. Isavuconazole is a newer broad-spectrum antifungal agent with promising efficacy and safety. However, there remains limited data to favor its use over current first-line agents. OBJECTIVES: We aimed to evaluate isavuconazole use and describe rates of associated breakthrough invasive fungal disease (bIFD). METHODS: A single-center, retrospective study was conducted to evaluate patients receiving isavuconazole for prophylaxis or treatment of IFD between July 1, 2017 and December 31, 2018. Patient-related and outcomes data were extracted from electronic medical records. Descriptive statistics were used to analyze our findings. RESULTS: A total of 54 patients received 61 isavuconazole courses. Isavuconazole was most commonly prescribed for primary prophylaxis in the acute myeloid leukemia (AML) and allogeneic hematopoietic stem cell transplant (HSCT) population along with treatment for possible invasive fungal disease. The primary reasons for choosing isavuconazole included QTc shortening effects, decreased risk of acute kidney injury, broader spectrum of activity, and concern for breakthrough invasive fungal disease on a different prophylactic agent. We found a breakthrough rate of 8.5% for patients and 7.8% for courses. CONCLUSIONS: Isavuconazole appears to be a promising alternative for prophylaxis and treatment of invasive fungal disease. We observed similar bIFD rates and improved tolerability when compared to historical data for posaconazole and voriconazole.

Advancing organ transplantation through HIV-to-HIV transplantation.

PURPOSE OF REVIEW: Persons living with HIV (PLWH) have a life expectancy that is nearly equivalent to the general population, and thus are facing health conditions associated with normal aging as well as long-term HIV infection. End-organ disease is associated with significant morbidity and mortality and solid organ transplantation (SOT) may be a viable option for many PLWH. We review the history and recent updates in SOT in PLWH, specifically focusing on HIV-to-HIV transplantation. RECENT FINDINGS: Following promising data out of South Africa and to expand the donor pool, the United States passed the HIV Organ Procurement Equity (HOPE) Act, allowing for HIV-to-HIV SOT. Preliminary data to date, especially in HIV-to-HIV kidney transplantation, suggest overall excellent patient and graft survival outcomes with no HIV breakthrough infection. SUMMARY: Preliminary HIV D+R+ SOT data to date suggest promising patient outcomes and no significant adverse events to recipients or living donors. This is an important step in expanding the donor pool and increasing opportunity for SOT in PLWH.

Treatment with convalescent plasma in solid organ transplant recipients with COVID-19: Experience at large transplant center in New York City.

Solid organ transplant (SOT) recipients may be at higher risk for poor outcomes with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Convalescent plasma is an investigational therapy that may benefit immunosuppressed patients by providing passive immunity. Convalescent plasma was administered to hospitalized patients with coronavirus disease-2019 (COVID-19) at an academic transplant center in New York City. Eligible patients were hospitalized and required to have positive nasopharyngeal polymerase chain reaction (PCR) diagnosis of SARS-CoV-2 infection, be at least 18 years old, and have either dyspnea, blood oxygen saturation ≤ 93% on ambient air, respiratory frequency ≥ 30 breaths/min, partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300, or lung infiltrates > 50%. Thirteen SOT recipients received convalescent plasma from April 9, 2020, to May 17, 2020. The median time from symptom onset to plasma infusion was 8 days. Eight of 13 patients (62%) had de-escalating oxygenation support by day 7 post-convalescent plasma. Nine (69%) patients were discharged, 1 (7%) patients remain hospitalized, and 3 (23%) patients died. This series supports the need for additional studies on convalescent plasma use in SOT recipients with COVID-19 to better determine efficacy and identify patients who are likely to benefit.

Predictors of mortality in solid organ transplant recipients with bloodstream infections due to carbapenemase-producing Enterobacterales: The impact of cytomegalovirus disease and lymphopenia.

Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score ≥8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score ≥8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.

Methicillin-resistant Staphylococcus aureus in solid organ transplantation-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice review the epidemiology, diagnosis, prevention, and management of methicillin-resistant Staphylococcus aureus (MRSA) infections in solid organ transplantation. Despite an increasing armamentarium of antimicrobials active against MRSA, improved diagnostic tools, and overall declining rates of infection, MRSA infections remain a substantial cause of morbidity and mortality in solid organ transplant recipients. Pre- and post-transplant MRSA colonization is a significant risk factor for post-transplant MRSA infection. The preferred initial treatment of MRSA bacteremia remains vancomycin. Hand hygiene, chlorhexidine bathing in the ICU, central-line bundles that focus on reducing unnecessary catheter use, disinfection of patient equipment, and the environment along with antimicrobial stewardship are all aspects of an infection prevention approach to prevent MRSA transmission and decrease healthcare-associated infections.

Screening recipients of increased risk donor organs: A multicenter retrospective study.

Organ Procurement & Transplantation Network policy requires post-transplant screening of recipients of organs from donors at increased risk for transmission of HIV, hepatitis B virus, and hepatitis C virus. Available data suggest that follow-up testing of recipients is not routinely conducted. Data on increased risk donors and recipients of their organs from 2008 to 2012 were retrospectively collected from 6 transplant centers after IRB approval. Descriptive statistics were performed. About 363 (60%) recipients were screened for transmission of HIV, HBV, and/or HCV at some time point; 257 (70.8%) within 90 days of transplant. The type of test used to screen for infection was variable with many recipients (25%-43%) screened with serology alone. Our results reveal that post-transplant screening for HIV, HBV, and HCV in recipients of increased risk donor organs did not universally occur and testing methods were variable.

18F-FDG PET/CT in left ventricular assist device infections: In-depth characterization and clinical implications.

BACKGROUND: Previous retrospective studies suggest a good diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET)/computed tomography (CT) in left ventricular assist device (LVAD) infections. Our aim was to prospectively evaluate the role of PET/CT in the characterization and impact on clinical management of LVAD infections. METHODS: A total of 40 patients (aged 58 [53-62] years) with suspected LVAD infection and 5 controls (aged 69 [64-71] years) underwent 18F-FDG-PET/CT. Four LVAD components were evaluated: exit site and subcutaneous driveline (peripheral), pump pocket, and outflow graft. The location with maximal uptake was considered the presumed site of infection. Infection was confirmed by positive culture (exit site or blood) and/or surgical findings. RESULTS: Visual uptake was present in 40 patients (100%) in the infection group vs 4 (80%) control subjects. For each individual component, the presence of uptake was more frequent in the infection than in the control group. The location of maximal uptake was most frequently the pump pocket (48%) in the infection group and the peripheral components (75%) in the control group. Maximum standard uptake values (SUVmax) were higher in the infection than in the control group: SUVmax (average all components): 6.9 (5.1-8.5) vs 3.8 (3.7-4.3), p = 0.002; SUVmax (location of maximal uptake): 10.6 ± 4.0 vs 5.4 ± 1.9, p = 0.01. Pump pocket infections were more frequent in patients with bacteremia than without bacteremia (79% vs 31%, p = 0.011). Pseudomonas (32%) and methicillin-susceptible Staphylococcus aureus (29%) were the most frequent pathogens and were associated with pump pocket infections, while Staphylococcus epidermis (11%) was associated with peripheral infections. PET/CT affected the clinical management of 83% of patients with infection, resulting in surgical debridement (8%), pump exchange (13%), and upgrade in the transplant listing status (10%), leading to 8% of urgent transplants. CONCLUSIONS: 18F-FDG-PET/CT enables the diagnosis and characterization of the extent of LVAD infections, which can significantly affect the clinical management of these patients.

Wait Time Advantage for Transplant Candidates With HIV Who Accept Kidneys From Donors With HIV Under the HOPE Act.

BACKGROUND: Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D + ), it is crucial to understand whether this has impacted transplant rates for this population. METHODS: Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D + kidneys (HOPE) compared with 46 025 candidates not listed for D + kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D + , false-positive [FP; donor with false-positive HIV testing], D - [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure. RESULTS: HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P < 0.001). Within 4.5 y, 70% of HOPE candidates received a KT (41% D + , 34% D - , 20% FP, 4% LD) versus 43% of non-HOPE candidates (74% D - , 26% LD). Conversely, 22% of HOPE candidates versus 39% of non-HOPE candidates died or were removed from the waitlist. Median KT wait time was 10.3 mo for HOPE versus 60.8 mo for non-HOPE candidates ( P < 0.001). After adjustment, HOPE candidates had a 3.30-fold higher KT rate (adjusted hazard ratio = 3.30, 95% confidence interval, 2.14-5.10; P < 0.001). CONCLUSIONS: Listing for D + kidneys within HOPE trials was associated with a higher KT rate and shorter wait time, supporting the expansion of this practice for candidates with HIV.

Relationship of white potato to other vegetable consumption by schoolchildren and adolescents in the U.S.A: National Health and Nutrition Examination Survey, 2003-2008.

OBJECTIVE: Intake of white potatoes in and out of school was estimated to provide context for a recent proposal by the U.S. Department of Agriculture to limit provision of white potatoes in U.S. school meals. DESIGN: Mean daily servings of white potatoes and other vegetables consumed in and out of school for school-aged children were estimated from two days of 24 h dietary recall data from the National Health and Nutrition Examination Surveys (NHANES). Total energy intake and percentage energy contribution from discretionary oils and solid fats were also estimated for all white potato dishes consumed. SETTING: The NHANES is nationally representative of the U.S. civilian noninstitutionalized population. SUBJECTS: Children and adolescents aged 6­19 years (n 8466) from three combined NHANES cycles (2003­2004, 2005­2006 and 2007­2008). RESULTS: White potatoes represented 32% of all vegetable servings consumed by U.S. children and adolescents. Preparations high in fats and oils, including French fries, were most popular both in and out of school. Mean consumption of white potatoes obtained from school cafeterias was approximately 0.05 servings/d among all children and adolescents, and about 0.15 servings/d among children and adolescents acquiring at least one item from the school cafeteria, implying current weekly intake levels well below the limit of 2 servings/week proposed by the U.S. Department of Agriculture. CONCLUSIONS: Although white potatoes represent a substantial proportion of vegetable consumption among school-aged children, it is unclear that proposed limits would influence white potato intake from school cafeterias. Policy makers should consider targeting preparation methods to improve the healthfulness of white potato dishes.

Highly sensitive technique for detection of adulterants in centella herbal samples using surface enhanced Raman spectroscopy (SERS).

The trace level detection of adulterants in food, nutritional supplements and medicinal herbs is highly challenging in the field of food processing and herbal industries. In addition, laborious sample processing procedures and well trained personnel are required to analyse the samples using conventional analytical equipments. In this study, a highly sensitive technique with minimal sampling processes and human intervention is proposed for the trace amount detection of pesticidal residues in centella powder. Herein, graphene oxide gold (GO-Au) nanocomposite coated parafilm is developed as substrate by simple dropcasting technique to facilitate dual surface enhanced Raman signal. The dual SERS enhancement involving chemical enhancement from graphene and electromagnetic signal enhancement from gold nanoparticles is utilized for detection of chlorpyrifos in the ppm level concentration. The flexible polymeric surfaces could be the better choice for SERS substrates due to their inherent properties such as flexibility, transparency, roughness and hydrophobicity. Among the various types of flexible substrates explored, GO-Au nanocomposites coated parafilm substrates showed better Raman signal enhancement. Parafilm coated with GO-Au nanocomposites is successful in achieving detection limits down to 0.1 ppm of chlorpyrifos in centella herbal powder sample. Thus, the fabricated parafilm based GO-Au SERS substrates could be used as a screening tool at quality control of herbal product manufacturing sectors for trace level detection of adulterants in herbal samples from their unique chemical and structural information.

New revelations from the zone of uncertainty.

In this issue of Neuron, Schroeder et al.1 provide the first functional account of inhibitory signaling from the zona incerta to neocortex in behaving animals. Incertocortical afferents exhibit bidirectional plasticity during threat learning, highlighting a distinct top-down signaling regime.

An unusual cause of pyrexia of unknown origin with sepsis: A diagnostic challenge.

Sphingobacterium species are ubiquitous and are abundant in nature and rarely involved in causing human infections. A 62-year-old man presented with recurrent episodes of high fever up to 40 â€‹°C accompanied by rigors, sweating, and malaise for the past 4 weeks. After a thorough workup, only elevated C-reactive protein with a leucocytosis was evident. Blood culture showed growth of Gram-negative bacilli which was identified as spingobacterium spiritivorum. Although S. spiritivorum is rare, with limited cases reported in the literature, it must be considered as a causative organism in patients with persistent fevers with sepsis.