Characterizing two-mode-squeezed light from four-wave mixing in rubidium vapor for quantum sensing and information processing.

We present a study of homodyne measurements of two-mode, vacuum-seeded, quadrature-squeezed light generated by four-wave mixing in warm rubidium vapor. Our results reveal that the vacuum squeezing can extend down to measurement frequencies of less than 1 Hz, and the squeezing bandwidth, similar to the seeded intensity-difference squeezing measured in this system, reaches up to approximately 20 MHz for typical pump parameters. By dividing the squeezing bandwidth into smaller frequency bins, we show that different sideband frequencies represent independent sources of two-mode squeezing. These properties are useful for quantum sensing and quantum information processing applications. We also investigate the impact of group velocity delays on the correlations in the system, which allows us to optimize the useful spectrum.

Cognitive Behavioral Therapy for Insomnia Self-Management Mobile Apps: A Review of Efficacy and Quality.

Cognitive behavioral therapy for insomnia (CBT-I) is the recommended treatment for insomnia, yet multiple barriers limit utilization. Digital CBT-I may present a solution, though related reviews have focused on Internet-based delivery rather than app use. The high utilization of health apps and prevalence of sleep apps indicate the need to equip clinicians with app-specific research. Toward this end, we reviewed efficacy and quality data on self-management CBT-I smartphone apps, revealing efficacy research on eleven apps, five of which were publicly available. While preliminary, these efficacy studies showed consistent positive findings. When examining quantitative quality indicators for the five publicly available apps, two had consistent data. Overall, two apps, CBTi Coach and Insomnia Coach, had positive, empirical findings across all efficacy and quality assessment approaches. We provide recommendations to guide clinician decision making regarding CBT-I self-management apps based on the literature and publicly available methods of app evaluations.

Analgesic Activity of 5-Acetamido-2-Hydroxy Benzoic Acid Derivatives and an In-Vivo and In-Silico Analysis of Their Target Interactions.

The design, synthesis, and evaluation of novel non-steroidal anti-inflammatory drugs (NSAIDs) with better activity and lower side effects are big challenges today. In this work, two 5-acetamido-2-hydroxy benzoic acid derivatives were proposed, increasing the alkyl position (methyl) in an acetamide moiety, and synthesized, and their structural elucidation was performed using 1H NMR and 13C NMR. The changes in methyl in larger groups such as phenyl and benzyl aim to increase their selectivity over cyclooxygenase 2 (COX-2). These 5-acetamido-2-hydroxy benzoic acid derivatives were prepared using classic methods of acylation reactions with anhydride or acyl chloride. Pharmacokinetics and toxicological properties were predicted using computational tools, and their binding affinity (kcal/mol) with COX-2 receptors (Mus musculus and Homo sapiens) was analyzed using docking studies (PDB ID 4PH9, 5KIR, 1PXX and 5F1A). An in-silico study showed that 5-acetamido-2-hydroxy benzoic acid derivates have a better bioavailability and binding affinity with the COX-2 receptor, and in-vivo anti-nociceptive activity was investigated by means of a writhing test induced by acetic acid and a hot plate. PS3, at doses of 20 and 50 mg/kg, reduced painful activity by 74% and 75%, respectively, when compared to the control group (20 mg/kg). Regarding the anti-nociceptive activity, the benzyl showed reductions in painful activity when compared to acetaminophen and 5-acetamido-2-hydroxy benzoic acid. However, the proposed derivatives are potentially more active than 5-acetamido-2-hydroxy benzoic acid and they support the design of novel and safer derivative candidates. Consequently, more studies need to be conducted to evaluate the different pharmacological actions, the toxicity of possible metabolites that can be generated, and their potential use in inflammation and pain therapy.

3D printing stretchable and compressible porous structures by polymerizable emulsions for soft robotics.

UV-curable 3D printing compositions for the fabrication of stretchable and flexible porous structures for soft robotics are presented. The stereolithography-based printing compositions are water-in-oil (W/O) emulsions in which water droplets are the pore-forming material, and the continuous phase is a stretchable polyurethane diacrylate (PUA). The porosity of the printed objects is controlled by the material's micro-porosity and by the macro-porosity obtained by a cellular design. The mechanical behavior can be tailored by the composition of the emulsion, providing both compliance and strength while utilizing a unique optimization methodology for fitting the ink to the 3D printer. This approach enables developing materials having superior mechanical properties, with the highest reported elongation-at-break for 3D printed porous structures, 450%. The emulsion-based printing compositions were utilized for fabricating a soft robotic gripper with unique actuation performance that could not be obtained with commonly used materials.

HMGB1 acts as an agent of host defense at the gut mucosal barrier.

Mucosal barriers provide the first line of defense between internal body surfaces and microbial threats from the outside world. 1 In the colon, the barrier consists of two layers of mucus and a single layer of tightly interconnected epithelial cells supported by connective tissue and immune cells. 2 Microbes colonize the loose, outer layer of colonic mucus, but are essentially excluded from the tight, epithelial-associated layer by host defenses. 3 The amount and composition of the mucus is calibrated based on microbial signals and loss of even a single component of this mixture can destabilize microbial biogeography and increase the risk of disease. 4-7 However, the specific components of mucus, their molecular microbial targets, and how they work to contain the gut microbiota are still largely unknown. Here we show that high mobility group box 1 (HMGB1), the prototypical damage-associated molecular pattern molecule (DAMP), acts as an agent of host mucosal defense in the colon. HMGB1 in colonic mucus targets an evolutionarily conserved amino acid sequence found in bacterial adhesins, including the well-characterized Enterobacteriaceae adhesin FimH. HMGB1 aggregates bacteria and blocks adhesin-carbohydrate interactions, inhibiting invasion through colonic mucus and adhesion to host cells. Exposure to HMGB1 also suppresses bacterial expression of FimH. In ulcerative colitis, HMGB1 mucosal defense is compromised, leading to tissue-adherent bacteria expressing FimH. Our results demonstrate a new, physiologic role for extracellular HMGB1 that refines its functions as a DAMP to include direct, virulence limiting effects on bacteria. The amino acid sequence targeted by HMGB1 appears to be broadly utilized by bacterial adhesins, critical for virulence, and differentially expressed by bacteria in commensal versus pathogenic states. These characteristics suggest that this amino acid sequence is a novel microbial virulence determinant and could be used to develop new approaches to diagnosis and treatment of bacterial disease that precisely identify and target virulent microbes.

Leishmania infantum Axenic Amastigotes Induce Human Neutrophil Extracellular Traps and Resist NET-Mediated Killing.

Neutrophils are multifaceted cells that, upon activation, release meshes of chromatin associated with different proteins, known as neutrophil extracellular traps (NETs). Leishmania amazonensis promastigotes and amastigotes induce NET release, and we have identified the signaling pathways involved in NET extrusion activated by promastigotes. Amastigotes maintain the infection in vertebrate hosts, and we have shown the association of NETs with amastigotes in human biopsies of cutaneous leishmaniasis. However, the interaction of amastigotes and neutrophils remains poorly understood. Our study aimed to characterize the pathways involved in the formation of NETs induced by axenic amastigotes from L. infantum, the causal agent of visceral leishmaniasis. Human neutrophils pretreated with signaling pathway inhibitors were incubated with amastigotes, and NET release was quantified in the culture supernatant. Amastigote viability was checked after incubation with NETs. We found that the release of NETs by neutrophils stimulated with these amastigotes requires the participation of elastase and peptidyl arginine deaminase and the involvement of PI3K, ROS, and calcium. Moreover, amastigotes are not susceptible to NET-mediated killing. Altogether, these findings improve our comprehension of the signaling pathways implicated in the interaction between amastigotes and human neutrophils.

Chemical composition, antinociceptive and anti-inflammatory activities of the curzerene type essential oil of Eugenia uniflora from Brazil.

ETHNOPHARMACOLOGICAL RELEVANCE: The Eugenia uniflora leaf infusion is widely used in folk medicine to treat gastroenteritis, fever, hypertension, inflammatory and diuretic diseases. AIM OF THE STUDY: This work evaluated the acute oral toxic, antinociceptive, and anti-inflammatory activities of the curzerene chemotype of Eugenia uniflora essential oil (EuEO). MATERIAL AND METHODS: EuEO was obtained by hydrodistillation and analyzed by GC and GC-MS. The antinociceptive action in mice was evaluated for the peripheral and central analgesic activity using abdominal contortion and hot plate tests (50, 100, and 200 mg/kg); xylene-induced ear swelling was carried out for the nociception test, and carrageenan-induced cell migration test. Spontaneous locomotor activity was assessed in the open field test to rule out any nonspecific sedative or muscle relaxant effects of EuEO. RESULTS: The EuEO displayed a yield of 2.6 ± 0.7%. The major compounds classes were oxygenated sesquiterpenoids (57.3 ± 0.2%), followed by sesquiterpene hydrocarbons (16.4 ± 2.6). The chemical constituents with the highest concentrations were curzerene (33.4 ± 8.5%), caryophyllene oxide (7.6 ± 2.8%), ß-elemene (6.5 ± 1.8%), and E-caryophyllene (4.1 ± 0.3%). Oral treatment with EuEO, at doses of 50, 300, and 2000 mg/kg, did not change the behavior patterns or mortality of the animals. EuEO (300 mg/kg) did not cause a reduction in the number of crossings in the open field compared to the vehicle group. The aspartate aminotransferase (AST) level was higher in EuEO-treated groups (50 and 2000 mg/kg) when compared to the control group (p < 0.05). EuEO, at doses of 50, 100, and 200 mg/kg, reduced the number of abdominal writhings by 61.66%, 38.33%, and 33.33%. EuEO did not show increased hot plate test time latency in any of the intervals analyzed. At 200 mg/kg, EuEO decreased paw licking time, with inhibition of 63.43%. In formalin-induced acute pain, EuEO decreased paw licking time at doses of 50, 100, and 200 mg/kg in the first phase, with inhibition of 30.54%, 55.02%, and 80.87%. The groups treated with EuEO at doses of 50, 100, and 200 mg/kg showed ear edema reduction of 50.26%, 55.17%, and 51.31%, respectively. Moreover, EuEO inhibited leukocyte recruitment only at a dose of 200 mg/kg. The inhibitory values of leukocyte recruitment after 4 h of carrageenan application were 4.86%, 4.93%, and 47.25% for 50, 100, and 200 mg/kg of essential oil, respectively. CONCLUSION: The EuEO, curzerene chemotype, has significant antinociceptive and anti-inflammatory activities and low acute oral toxicity. This work confirms the antinociceptive and anti-inflammatory of this species as the traditional use.

Child and family perceptions of satisfaction with neutropenia management in pediatric acute myeloid leukemia.

PURPOSE: Chemotherapy for pediatric acute myeloid leukemia (AML) is very intensive and many, but not all centers, require extended hospitalization until neutrophil recovery. Child and family preferences, beliefs, and experiences around hospitalization have not been systematically assessed. PATIENTS AND METHODS: We recruited children with AML and their parents from nine pediatric cancer centers across the United States for a qualitative interview about their experiences of neutropenia management. Interviews were analyzed using a conventional content analysis approach. RESULTS: Of 116 eligible individuals, 86 (74.1%) agreed to participate. Interviews were conducted with 32 children and 54 parents from 57 families. Of these 57 families, 39 were cared for as inpatients and 18 were managed as outpatients. A very high proportion of respondents in both groups reported satisfaction with the discharge management strategy recommended by the treating institution: 86% (57 individuals) of respondents who experienced inpatient management and 85% (17 individuals) of respondents who experienced outpatient management expressed satisfaction. Respondent perceptions associated with satisfaction related to safety (access to emergency interventions, infection risk, close monitoring) and psychosocial concerns (family separation, low morale, social support). Respondents believed it could not be assumed that all children would have the same experience due to varied life circumstances. CONCLUSION: Children with AML and their parents express a very high degree of satisfaction with the discharge strategy recommended by their treating institution. Respondents saw a nuanced tradeoff between patient safety and psychosocial concerns that was mediated by a child's life circumstances.

Climate Change, Fragility, and Child Mortality; Understanding the Role of Water Access and Diarrheal Disease Amongst Children Under Five During the MDG Era.

The present study examined the influence of improvements to Water, Sanitation, and Hygiene (WASH) infrastructure on rates of under-five mortality specifically from diarrheal disease amongst children in fragile states. The World Bank's Millennium Development Goals and Sustainable Development Goals both include a specific target of reduction in preventable disease amongst children, as well as goal to improve WASH. Although gains have been made, children under the age of five remain particularly vulnerable to diarrheal mortality in states identified as fragile. Increasingly, climate change is placing undue pressure on states labeled fragile due to their inability to properly prepare for, or respond to, natural disasters that further compromise WASH development and water safety. The impact of climate change upon child health outcomes is neither direct nor linear and necessitates a linkage framework that can account for complex pathways between environmental pressures and public health outcomes. The World Health Organization's Drive Force-Pressure-State-Exposure-Effect-Action conceptual framework was used to draw the connections between seemingly disparate, and highly nuanced, environmental, and social measures. Using a multilevel hierarchical model, this analysis used a publicly available UNICEF data set that reported rates of mortality specifically from diarrheal disease amongst children age five and younger. All 171 formally recognized countries were included, which showed a decline in diarrheal disease over time when investments in WASH infrastructure are compared. As states experience increased pressure because of climate change, this area of intervention is key for immediate health and safety of children under-five, as well as assisting fragile states long-term as the move toward stability.

Organic ultraviolet filter mixture promotes bleaching of reef corals upon the threat of elevated seawater temperature.

Global reef degradation is a critical environmental health issue that has triggered intensive research on ocean warming, but the implications of emerging contaminants in coral habitats are largely overlooked. Laboratory experiments assessing organic ultraviolet (UV) filter exposure have shown that these chemicals negatively affect coral health; their ubiquitous occurrence in association with ocean warming may pose great challenges to coral health. We investigated both short- (10-day) and long-term (60-day) single and co-exposures of coral nubbins to environmentally relevant organic UV filter mixtures (200 ng/L of 12 compounds) and elevated water temperatures (30 °C) to investigate their effects and potential mechanisms of action. The initial 10-day exposure of Seriatopora caliendrum resulted in bleaching only under co-exposure conditions (compounds + temperature). The 60-day mesocosm study entailed the same exposure settings with nubbins of three species (S. caliendrum, Pocillopora acuta and Montipora aequituberculata). Bleaching (37.5 %) and mortality (12.5 %) of S. caliendrum were observed under UV filter mixture exposure. In the co-exposure treatment, 100 % S. caliendrum and P. acuta bleached associating with 100 % and 50 % mortality, respectively, and significant increase of catalase activities in P. acuta and M. aequituberculata nubbins were found. Biochemical and molecular analyses indicated significant alteration of oxidative stress and metabolic enzymes. The results suggest that upon the adverse effects of thermal stress, organic UV filter mixture at environmental concentrations can cause bleaching in corals by inducing a significant oxidative stress and detoxification burden, suggesting that emerging contaminants may play a unique role in global reef degradation.

Multi-macromolecular Extraction from Endosymbiotic Anthozoans.

Obligately symbiotic associations between reef-building corals (anthozoan cnidarians) and photosynthetically active dinoflagellates of the family Symbiodiniaceae comprise the functional basis of all coral reef ecosystems. Given the existential threats of global climate change toward these thermo-sensitive entities, there is an urgent need to better understand the physiological implications of changes in the abiotic milieu of scleractinian corals and their mutualistic algal endosymbionts. Although initially slow to leverage the immense breakthroughs in molecular biotechnology that have benefited humankind, coral biologists are making up for lost time in exploiting an array of ever-advancing molecular tools for answering key questions pertaining to the survival of corals in an ever-changing world. In order to comprehensively characterize the multi-omic landscape of the coral holobiont-the cnidarian host, its intracellular dinoflagellates, and a plethora of other microbial constituents-I introduce a series of protocols herein that yield large quantities of high-quality RNA, DNA, protein, lipids, and polar metabolites from a diverse array of reef corals and endosymbiotic sea anemones. Although numerous published articles in the invertebrate zoology field feature protocols that lead to sufficiently high yield of intact host coral macromolecules, through using the approach outlined herein one may simultaneously acquire a rich, multi-compartmental biochemical pool that truly reflects the complex and dynamic nature of these animal-plant chimeras.

Risk of bacterial bloodstream infection does not vary by central-line type during neutropenic periods in pediatric acute myeloid leukemia.

BACKGROUND: Bloodstream infections (BSIs) are a frequent cause of morbidity in patients with acute myeloid leukemia (AML), due in part to the presence of central venous access devices (CVADs) required to deliver therapy. OBJECTIVE: To determine the differential risk of bacterial BSI during neutropenia by CVAD type in pediatric patients with AML. METHODS: We performed a secondary analysis in a cohort of 560 pediatric patients (1,828 chemotherapy courses) receiving frontline AML chemotherapy at 17 US centers. The exposure was CVAD type at course start: tunneled externalized catheter (TEC), peripherally inserted central catheter (PICC), or totally implanted catheter (TIC). The primary outcome was course-specific incident bacterial BSI; secondary outcomes included mucosal barrier injury (MBI)-BSI and non-MBI BSI. Poisson regression was used to compute adjusted rate ratios comparing BSI occurrence during neutropenia by line type, controlling for demographic, clinical, and hospital-level characteristics. RESULTS: The rate of BSI did not differ by CVAD type: 11 BSIs per 1,000 neutropenic days for TECs, 13.7 for PICCs, and 10.7 for TICs. After adjustment, there was no statistically significant association between CVAD type and BSI: PICC incident rate ratio [IRR] = 1.00 (95% confidence interval [CI], 0.75-1.32) and TIC IRR = 0.83 (95% CI, 0.49-1.41) compared to TEC. When MBI and non-MBI were examined separately, results were similar. CONCLUSIONS: In this large, multicenter cohort of pediatric AML patients, we found no difference in the rate of BSI during neutropenia by CVAD type. This may be due to a risk-profile for BSI that is unique to AML patients.

The Identification and Treatment of Common Skin Infections.

Skin conditions are a common problem addressed by medical providers. Up to 25% of individuals in the United States will seek attention for these conditions each year. The same problem occurs in the athletic training room, where athletes with infectious skin conditions can be seen. Most conditions are simple and can be treated without concern for spread to susceptible athletes. However, others can be quite serious and spread rapidly through a team and opponents during competition. Knowledge of the different types of skin infections is necessary to help treat these athletes and prevent spread to others. With proper diagnosis and treatment, certified athletic trainers can keep the athlete off the field of play for a minimum period and prevent transmission.

Modes and Mechanisms of Pacific Decadal-Scale Variability.

The modes of Pacific decadal-scale variability (PDV), traditionally defined as statistical patterns of variance, reflect to first order the ocean's integration (i.e., reddening) of atmospheric forcing that arises from both a shift and a change in strength of the climatological (time-mean) atmospheric circulation. While these patterns concisely describe PDV, they do not distinguish among the key dynamical processes driving the evolution of PDV anomalies, including atmospheric and ocean teleconnections and coupled feedbacks with similar spatial structures that operate on different timescales. In this review, we synthesize past analysis using an empirical dynamical model constructed from monthly ocean surface anomalies drawn from several reanalysis products, showing that the PDV modes of variance result from two fundamental low-frequency dynamical eigenmodes: the North Pacific-central Pacific (NP-CP) and Kuroshio-Oyashio Extension (KOE) modes. Both eigenmodes highlight how two-way tropical-extratropical teleconnection dynamics are the primary mechanisms energizing and synchronizing the basin-scale footprint of PDV. While the NP-CP mode captures interannual- to decadal-scale variability, the KOE mode is linked to the basin-scale expression of PDV on decadal to multidecadal timescales, including contributions from the South Pacific.

Chemical composition and antinociceptive and anti-inflammatory activity of the essential oil of Hyptis crenata Pohl ex Benth. from the Brazilian Amazon.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaf tea of Hyptis crenata has its practical use in the Brazilian Amazon for treating gastrointestinal and liver disorders, sweating induction, and as an anti-inflammatory. AIM OF THE STUDY: Evaluation of the chemical composition, acute oral toxicity, and antinociceptive and anti-inflammatory activities of the H. crenata essential oil. MATERIAL AND METHODS: The essential oil was hydrodistilled and analyzed by GC and GC-MS. The antinociceptive action in mice was evaluated for the peripheral and central analgesic activity (abdominal contortion and hot plate tests), and the xylene-induced ear swelling was carried out for the nociception test. RESULTS: Oxygenated monoterpenes (53.0%) and monoterpene hydrocarbons (38.9%) predominated in the H. crenata oil, being 1,8-cineo1e (35.9%), α-pinene (20.8%), camphor (10.0%), and ß-pinene (7.3%) their primary constituents. The oral oil administration in the mice did not display changes in behavior patterns or animal mortality at 300 and 2000 mg/kg doses. The control group's biochemical parameters (ALP, AST, ALT) displayed a statistical difference from the treated group, unlike the renal parameters, which showed no variation between the groups. Oil reduced the abdominal contortions at doses of 100 (79.5%) and 300 mg/kg (44.4%), while with endodontacin, the dose was 5 mg/kg (75.2%). In addition, the oil could not decrease the paw licking/biting time at doses of 30, 100, and 300 mg/kg. However, it showed a significant antinociceptive effect on the second phase in the formalin test inhibiting licking time, with a reduction of 50.8% (30 mg/kg), 63.4% (100 mg/kg), 58.0% (300 mg/kg), and morphine (4 mg/kg, 78.3%). The oil administration produced significant inhibition of ear edema at all tested doses, with a better effect produced at 30 mg/kg (64.0% inhibition). CONCLUSION: The oil of Hyptis crenata, rich in 1,8-cineole, camphor, α-pinene, and ß-pinene, totaling 74%, displayed low acute toxicity and significant anti-inflammatory activity, with peripheral and no central antinociceptive action. Thus, these results show an actual perspective on using H. crenata oil in developing a phytotherapeutic product.

Justification Of Empiric Methodology to Determine Dexmedetomidine Dose for the TREX Study.

INTRODUCTION: Dexmedetomidine is the sedative agent administered in combination with remifentanil and low dose of sevoflurane in the interventional arm of the ongoing TREX trial (Trial Remifentanil DExmedetomidine). The TREX pilot study (published in Paediatr Anaesth 2019;29:59-67) established infusion rates higher than those initially proposed. This could be attributed to an inappropriate target concentration for sedation or incorrect initial pharmacokinetic parameter estimates. METHODS: The TREX study is a Phase III, randomized, active controlled, parallel group, blinded evaluator, multicentre, superiority trial comparing neurological outcome after standard sevoflurane anaesthesia with dexmedetomidine/remifentanil and low dose sevoflurane anaesthesia in children aged less than 2 years undergoing anaesthesia of 2 hours or longer. In this report, dexmedetomidine pharmacokinetics were analysed in the interventional arm of the Italian population. RESULTS: There were 162 blood samples from 32 infants (22 male and 10 female). The median (IQR) age was 12 (5.2-15.5) months, weight 9.9 (7.3-10.8) kg. Duration of anaesthesia ranged from 2-6 hours. None of the children were born premature (median postnatal age 39 weeks, IQR 38-40 weeks). A 3-compartment PK model that incorporated allometric scaling and a maturation function demonstrated plasma concentration observations from the current Italian arm of the TREX study were consistent with those predicted by a "universal" model using pooled data obtained from neonates to adults. CONCLUSIONS: This current PK analysis from the Italian arm of the TREX study confirms that plasma concentration of dexmedetomidine is predictable using known covariates such as age and size. The initial target concentration (0.6 µg.L-1 ) used to sedate children cared for in the intensive care after cardiac surgery was inadequate for infants in the current TREX study. A target concentration 1 mcg.L-1 , corresponding to a loading dose of 1 mcg.kg-1 followed by an infusion of 1 mcg.kg-1 .hour-1 , provided adequate sedation.

Cancer care for Ukrainian refugees: Strategic impact assessments in the early days of the conflict.

BACKGROUND: The invasion of Ukraine by Russia in February 2022 has resulted in destruction of healthcare infrastructure and triggered the largest wave of internally displaced populations and refugees since World War Two. Conflicts in transitioned countries such as Ukraine create new non-communicable disease (NCD) challenges, especially for cancer care for refugees and humanitarian assistance in host countries. In the early days, rapid attempts were made to model possible impacts. METHODS: By evaluating open source intelligence used in the first three months of the conflict through snowball search methods, we aimed to address: (i) burden of cancer in Ukrainian population, specifically considering translating to the refugees population, and its cancer care capacity; ii) baseline capacity/strengths of cancer systems in initial host countries. Moreover, using a baseline scenario based on crude cancer incidence in Ukraine, and considering data from UNHCR, we estimated how cancer cases would be distributed across host countries. Finally, a surveillance assessment instrument was created, intersecting health system's capacity and influx of internally displaced populations and refugees. FINDINGS AND CONCLUSIONS: The total new cancer patients per month in pre-conflict Ukraine was estimated as 13,106, of which < 1 % are paediatric cases. The estimated cancer cases in the refugee population (combining prevalent and incident), assuming 7.5 million refugees by July 2022 and a female:male ratio of 9:1, was 33,121 individuals (Poland: 19284; Hungary: 3484; Moldova: 2651; Slovakia: 2421; Romania: 5281). According to our assessments, Poland is the only neighbouring country classified as green/yellow for cancer capacity, i.e. sufficient ablility to absorb additional burden into national health system; Slovakia we graded as yellow, Hungary and Romania as yellow/red and Moldova as red.

A phase 1b study of crenigacestat (LY3039478) in combination with gemcitabine and cisplatin or gemcitabine and carboplatin in patients with advanced or metastatic solid tumors.

BACKGROUND: Notch signaling plays an integral role in development and tissue homeostasis. Inhibition of Notch signaling has been identified as a reasonable target for oncotherapy. Crenigacestat (LY3039478) is a potent Notch inhibitor that decreases Notch signaling and its downstream biologic effects. METHODS: I6F-MC-JJCD was a multicenter, nonrandomized, open-label, phase 1b study with 5 separate, parallel dose escalations in patients with advanced or metastatic cancer from a variety of solid tumors followed by a dose-confirmation phase in pre-specified tumor types. This manuscript reports on 2 of 5 groups. The primary objective was to determine the recommended phase 2 dose of crenigacestat combined with other anticancer agents (gemcitabine/cisplatin or gemcitabine/carboplatin). Secondary objectives included evaluation of safety, tolerability, preliminary efficacy, and pharmacokinetics. RESULTS: Patients (N = 31) received treatment between November 2016 and July 2019. Dose-limiting toxicities occurred in 6 patients. The recommended phase 2 dose for crenigacestat was 50 mg TIW in Part 1 (combined with gemcitabine/cisplatin) and not established in Part 2 (combined with gemcitabine/carboplatin) due to poor tolerability. Patients had at least one treatment-emergent adverse event (TEAE), and most had Grade ≥ 3 TEAEs. Over 50% of the patients experienced gastrointestinal disorders (Grade ≥ 3). No patient had complete response; 5 patients had a partial response. Disease control rates were 62.5% (Part 1) and 60.0% (Part 2). CONCLUSION: This study demonstrated that the Notch inhibitor, crenigacestat, combined with different anticancer agents (gemcitabine, cisplatin, and carboplatin) was poorly tolerated and resulted in disappointing clinical activity in patients with advanced or metastatic solid tumors. CLINICALTRIALS: gov Identification Number: NCT02784795.

Acoustic and vibration isolation for a gravity gradiometer.

Vibration in the audio frequency band affects the performance of rotating gravity gradiometers used for airborne mineral exploration. This is probably due to translation to rotation coupling inside the gradiometer platform. It was found that the DC gravity gradient signal was proportional to the square of the third time derivative of position, or jerk squared. The demanding airborne environment for such instrumentation demands a light weight broadband acoustic shield and vibration isolator. This paper presents the design principles for such an isolator, based on vibration isolated spherical shell structures. Performance data are presented as well as flight test data that demonstrated a 14% gravity gradient noise reduction compared with an unshielded instrument.

House dust mite fauna characterization in the city of Rio de Janeiro and its importance in allergy diagnosis / Caracterização da fauna dos ácaros de poeira na cidade do Rio de Janeiro e sua importância em diagnósticos de alergias

Introduction: The home environment is one of the most favorable spaces for the development of mites because of its low light, humidity, and temperature. Thus, it contributes to the growing cases of allergies among atopic individuals. Objective: To investigate the faunal profile of house dust mites in the city of Rio de Janeiro and the allergenic potential in this region. Methods: Thirty dust samples were collected from homes in the city of Rio de Janeiro, and the species found were classified according to their morphology, family, and genus by classification key. For the collection region, the total protein level was assessed by the Lowry method and electrophoresis under denaturing conditions (SDSPAGE). Results: There was a predominance of Pyroglyphidae mites, accounting for 84.9% of samples; Tyrophagus putrescentiae accounted for 8%, Blomia tropicalis for 6%, Cheyletus malaccensis for 1%, and Acarus siro for 0.1%. The allergen protein content of the samples was the following: group 1 ­ 25 kDa (Der 1, Der p 1, and Blo t 1), group 2 ­ 15 kDa (Der f 2, Der 2, Tyr p 2, and Blo t 2), and group 3 ­ 29-30 kDa (Der f 3 and Blo t 3), which indicates that people in this region are susceptible to sensitization to these mites. Conclusion: Knowledge of the mite fauna in the region under study allows the guidance of health care professionals to perform skin tests for specific mites and conduct treatment according to the pool of mite extracts containing antigens, making immunotherapy more effective.

Introdução: O ambiente domiciliar é um dos espaços favoráveis para o desenvolvimento de ácaros, tendo em vista a baixa luminosidade, umidade e temperatura, o que contribui para os crescentes casos de alergias em indivíduos atópicos. Objetivo: Investigar o perfil faunístico dos ácaros na cidade do Rio de Janeiro e o potencial alergêncio para essa região. Métodos: Foram coletadas 30 amostras de poeira em residências na cidade do Rio de Janeiro, e as espécies encontradas foram classificadas quanto à morfologia, família e o gênero por chave de classificação. Para as regiões das coletas, a carga total de proteínas contendo os alérgenos foi determinada pelo método de Lowry e eletroforese em condições desnaturantes (SDS-PAGE). Resultados: Os resultados mostram a predominância de 84,9% de ácaros da família Pyroglyphidae; para os demais ácaros o percentual corresponde a 8% Tyrophagus putrescentiae, 6% Blomia tropicalis, 1% Cheyletus malaccensis, e 0,1% de Acarus siro. O conteúdo proteico alergêncio constituinte das amostras foram, grupo 1: 25 kDa (Der 1, Der p 1 e Blo t 1); grupo 2: 15 kDa (Der f 2, Der 2, Tyr p 2 e Blo t 2); e para o grupo 3: 29-30 kDa (Der f 3 e Blo t 3), o que indica uma região passível à sensibilização de indivíduos por estes ácaros. Conclusão: O conhecimento da acarofauna nas regiões em estudo permite orientar a comunidade médica quanto à realização de testes cutâneos, além da terapêutica a partir do pool de extratos de ácaros contendo os antígenos, a fim de tornar a imunoterapia mais eficaz.