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1.
Polymers (Basel) ; 16(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38475263

RESUMO

This study focuses on evaluating the fatigue life performance of 3D-printed polymer composites produced through the fused deposition modelling (FDM) technique. Fatigue life assessment is essential in designing components for industries like aerospace, medical, and automotive, as it provides an estimate of the component's safe service life during operation. While there is a lack of detailed research on the fatigue behaviour of 3D-printed polymer composites, this paper aims to fill that gap. Fatigue tests were conducted on the 3D-printed polymer composites under various loading conditions, and static (tensile) tests were performed to determine their ultimate tensile strength. The fatigue testing load ranged from 80% to 98% of the total static load. The results showed that the fatigue life of the pressed samples using a platen press was significantly better than that of the non-pressed samples. Samples subjected to fatigue testing at 80% of the ultimate tensile strength (UTS) did not experience failure even after 1 million cycles, while samples tested at 90% of UTS failed after 50,000 cycles, with the failure being characterized as splitting and clamp area failure. This study also included a lap shear analysis of the 3D-printed samples, comparing those that were bonded using a two-part Araldite glue to those that were fabricated as a single piece using the Markforged Mark Two 3D printer. In summary, this study sheds light on the fatigue life performance of 3D-printed polymer composites fabricated using the FDM technique. The results suggest that the use of post-printing platen press improved the fatigue life of 3D-printed samples, and that single printed samples have better strength of about 265 MPa than adhesively bonded samples in which the strength was 56 MPa.

2.
Addiction ; 119(6): 984-997, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38356084

RESUMO

BACKGROUND AND AMS: Despite the evident public health impact, the extent and patterns of alcohol use in the Eastern Mediterranean countries remain understudied. The latest estimation for the last 12-month use of alcohol in the region was 2.9% in 2016 by the World Health Organization. We reviewed the main indicators for alcohol consumption in the region since 2010. METHODS: We systematically searched on-line databases until September 2023, together with other global and regional sources for studies on the adult general population (aged ≥ 15 years) and young general populations (aged < 18 years) and studies on the treatment-seeking individuals with substance use in Eastern Mediterranean countries. Studies were included from 22 countries: Afghanistan, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, United Arab Emirates and Yemen. RESULTS: A total of 148 were included (n = 95 on the prevalence of alcohol use, n = 46 on the prevalence of alcohol use disorder, regular use and heavy episodic drinking, n = 35 on alcohol use pattern among people who use substances and one report on alcohol per capita consumption, n = 29 had data for more than one category). The pooled prevalence of the last 12-month alcohol use in the adult general population was 9.5% [95% confidence interval (CI) = 6.4-13.7] among males, 2.8% (95% CI = 1.3-5.5\) among females and 6.2% (95% CI = 3.9-9.6) in both sexes in the region, with notable subregional variations. Data on the prevalence of alcohol use disorder and heavy drinking were limited to several countries, with heterogeneous indicators. The pooled estimate of alcohol as the primary substance of use among treatment-seeking people who used substances was 16.9% (95% CI = 8.8-26.9). CONCLUSIONS: More than 30 million adults in the Eastern Mediterranean region used alcohol in the last 12 months, with a prevalence of 6.2%. This is far fewer than the global estimate of 43% of the population aged 15 years and above, but is approximately two times more than the previous estimate (2.9%), reported by the World Health Organization in 2016, which might show an increasing trend.


Assuntos
Consumo de Bebidas Alcoólicas , Alcoolismo , Humanos , Consumo de Bebidas Alcoólicas/epidemiologia , Oriente Médio/epidemiologia , Alcoolismo/epidemiologia , Masculino , Adulto , Consumo Excessivo de Bebidas Alcoólicas/epidemiologia , Feminino , Prevalência , Adolescente , Adulto Jovem , Região do Mediterrâneo/epidemiologia
3.
Nat Commun ; 15(1): 1158, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326354

RESUMO

Exploring non-genetic evolution of cell states during cancer treatments has become attainable by recent advances in lineage-tracing methods. However, transcriptional changes that drive cells into resistant fates may be subtle, necessitating high resolution analysis. Here, we present ReSisTrace that uses shared transcriptomic features of sister cells to predict the states priming treatment resistance. Applying ReSisTrace in ovarian cancer cells perturbed with olaparib, carboplatin or natural killer (NK) cells reveals pre-resistant phenotypes defined by proteostatic and mRNA surveillance features, reflecting traits enriched in the upcoming subclonal selection. Furthermore, we show that DNA repair deficiency renders cells susceptible to both DNA damaging agents and NK killing in a context-dependent manner. Finally, we leverage the obtained pre-resistance profiles to predict and validate small molecules driving cells to sensitive states prior to treatment. In summary, ReSisTrace resolves pre-existing transcriptional features of treatment vulnerability, facilitating both molecular patient stratification and discovery of synergistic pre-sensitizing therapies.


Assuntos
Células Matadoras Naturais , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Carboplatina , Fenótipo , Linhagem Celular Tumoral
4.
Immunity ; 56(12): 2816-2835.e13, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38091953

RESUMO

Cancer cells can evade natural killer (NK) cell activity, thereby limiting anti-tumor immunity. To reveal genetic determinants of susceptibility to NK cell activity, we examined interacting NK cells and blood cancer cells using single-cell and genome-scale functional genomics screens. Interaction of NK and cancer cells induced distinct activation and type I interferon (IFN) states in both cell types depending on the cancer cell lineage and molecular phenotype, ranging from more sensitive myeloid to less sensitive B-lymphoid cancers. CRISPR screens in cancer cells uncovered genes regulating sensitivity and resistance to NK cell-mediated killing, including adhesion-related glycoproteins, protein fucosylation genes, and transcriptional regulators, in addition to confirming the importance of antigen presentation and death receptor signaling pathways. CRISPR screens with a single-cell transcriptomic readout provided insight into underlying mechanisms, including regulation of IFN-γ signaling in cancer cells and NK cell activation states. Our findings highlight the diversity of mechanisms influencing NK cell susceptibility across different cancers and provide a resource for NK cell-based therapies.


Assuntos
Neoplasias Hematológicas , Neoplasias , Humanos , Células Matadoras Naturais , Neoplasias/genética , Apresentação de Antígeno , Genômica , Citotoxicidade Imunológica/genética , Linhagem Celular Tumoral
5.
Arch Suicide Res ; : 1-19, 2023 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-37837375

RESUMO

OBJECTIVE: An estimated 41,000 lives are lost to suicide each year in World Health Organization Eastern Mediterranean Region Office (WHO EMRO) countries. The objective of this study was to conduct a situation analysis for suicide and self-harm in the WHO EMRO region. METHODS: Data on suicide were obtained from the WHO Global Health Estimates for the years 2000-2019. Information on risk groups efforts to prevent self-harm and suicide in the EMRO region were retrieved through scientific studies, grey literature, and public websites. RESULTS: During 2000-2019, the age-standardized suicide rate was 6.7 per 100,000 inhabitants, albeit there are concerns regarding data quality. Self-harm and suicide remain criminal acts in more than half of the countries. Few countries have a national plan for prevention of suicide. Toxic agents, such as pesticides and black henna, are easily available and frequently used for suicide in some areas, as are firearms and self-immolation. Successful prevention measures include means restriction and psychosocial interventions after self-harm. CONCLUSION: Many WHO EMRO countries remain underserved in terms of mental health care. Decriminalization of suicide and means restriction might be further promoted. Online-based tools for mental health literacy and psychosocial therapy are other options to explore.


Suicidal behavior remains a criminal act in more than half of the WHO EMRO countries.Easily available toxic agents, such as pesticides and black henna, and firearms are common methods used for suicidal behavior in the WHO EMRO countries.Access to mental health care is limited in many of the WHO EMRO countries.Online-based psychoeducation and psychosocial intervention programs might be further explored as preventive efforts.

6.
Lancet Glob Health ; 11(8): e1225-e1237, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37474230

RESUMO

BACKGROUND: Considerable disease burden is attributed to injecting drug use (IDU). This regional systematic review and meta-analysis aimed to assess the prevalence of IDU and the characteristics of people who inject drugs in the 22 countries of the WHO Eastern Mediterranean region. METHODS: We conducted a systematic review and meta-analysis on the prevalence of IDU, estimation of the population size of people who inject drugs, the characteristics of people who inject drugs, commonly injected drugs, the prevalence of HIV, hepatitis C virus, and hepatitis B virus in people who inject drugs, and opioid agonist treatment and needle and syringe programme services. We searched PubMed, Web of Science, Scopus, Embase, and the Index Medicus for the Eastern Mediterranean Region for documents published between Jan 1, 2010, and April 17, 2022, with no language restrictions. We also searched government reports, civil society information, and UN websites and databases for grey literature published between Jan 1, 2010, and April 17, 2022. Documents were eligible if they reported or estimated an indicator of interest, or reported enough data to permit calculation of the indicator. We extracted data from the eligible documents and calculated national and regional estimates. FINDINGS: We identified 38 283 documents and included 201 documents in the systematic review. A total of 115 documents were included for the four outcomes for which meta-analyses were performed. The number of people who inject drugs was estimated as 864 597 (95% CI 641 909-1 205 255), amounting to a prevalence of 20·0 per 10 000 adults (95% CI 14·9-27·9) in the region. Among people who inject drugs, the prevalence of HIV was estimated as 19·22% (95% CI 12·86-26·36), hepatitis C virus as 44·82% (29·32-61·16), and hepatitis B virus as 2·66% (0·84-7·26). Countries varied greatly regarding the variables of interest and the availability of relevant data. Nine countries provided needle and syringe programme services and seven countries provided opioid agonist treatment services, mostly with very low, low, or unclear coverage. INTERPRETATION: The prevalence of IDU in the Eastern Mediterranean region is lower than the global mean, particularly among women. The HIV infection rate is higher than the global mean, and the hepatitis C virus infection rate is lower than the global mean. Harm-reduction services are underdeveloped. Data collection on IDU and provision of services need improvement in the region. FUNDING: World Health Organization. TRANSLATIONS: For the Arabic, Farsi and French translations of the abstract see Supplementary Materials section.


Assuntos
Usuários de Drogas , Infecções por HIV , Hepatite B , Hepatite C , Abuso de Substâncias por Via Intravenosa , Transtornos Relacionados ao Uso de Substâncias , Adulto , Humanos , Feminino , Hepacivirus , Infecções por HIV/epidemiologia , Infecções por HIV/tratamento farmacológico , Abuso de Substâncias por Via Intravenosa/epidemiologia , Prevalência , Analgésicos Opioides/uso terapêutico , Hepatite C/epidemiologia , Hepatite B/epidemiologia , Região do Mediterrâneo/epidemiologia , Vírus da Hepatite B
7.
Heliyon ; 9(6): e16738, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37313164

RESUMO

Kaolin clay-supported Zinc oxide (ZnO/KC) and ZnO NPs nanoparticles (NPs) were prepared by a chemical reduction process and used for the photodegradation of methyl red (MR) dye as a photocatalyst. Due to the interlayered porous structure of the KC, we achieved an extremely good association between ZnO NPs and KC. The product confirmation was conducted by Scanning electron microscopy (SEM), X-Ray diffraction (XRD), energy dispersive X-Ray (EDX), and Fourier transforms infrared (FTIR). SEM showed the irregular morphology of ZnO NPs, while ZnO/KC NCs were predominately round-shaped. Moreover, in both cases, NPs were present in both dispersed as well as agglomerated forms with an average particle size below 100 nm. The results acquired from photodegradation analyses show that ZnO NPs and ZnO/KC NCs degraded about 90 and 99% of MR dye respectively, under UV light in a short irradiation time of 10 min. The recovered and re-recovered ZnO NPs and ZnO/KC NCs also considerably photodegraded MR dye in an aqueous medium. The same NPs also exhibit promising bioactivities against two pathogenic bacteria, i.e., Citrobacter and Providencia. The antioxidant activity of ZnO/KC NCs reached to reasonable 70% compared to the 88% activity of the standard ascorbic acid.

8.
Heliyon ; 9(4): e14760, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37035375

RESUMO

The current study aims to investigate the effect of partial slip conditions over double diffusion convection. The phenomenon is applied with the inclined magnetic flux of peristaltic flow on Ellis nanofluid model in an asymmetric channel. The fundamental differential equations are constructed and solved through lubrication approximation that gives the coupled system of ordinary differential equations. This resultant system is further solved numerically, and graphic representation are used to physically comprehend the flow quantity data. The whole procedure is carried out under the trapping mechanism by drawing contour streamlines. The knowledge gained from this work will be useful in the creation of intelligent magneto-peristaltic pumps for specific heat and medication delivery phenomena.

9.
Nanomaterials (Basel) ; 13(5)2023 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-36903819

RESUMO

The present work has mathematically modeled the peristaltic flow in nanofluid by using thermal radiation, induced a magnetic field, double-diffusive convection, and slip boundary conditions in an asymmetric channel. Peristalsis propagates the flow in an asymmetric channel. Using the linear mathematical link, the rheological equations are translated from fixed to wave frames. Next, the rheological equations are converted to nondimensional forms with the help of dimensionless variables. Further, the flow evaluation is determined under two scientific assumptions: a finite Reynolds number and a long wavelength. Mathematica software is used to solve the numerical value of rheological equations. Lastly, the impact of prominent hydromechanical parameters on trapping, velocity, concentration, magnetic force function, nanoparticle volume fraction, temperature, pressure gradient, and pressure rise are evaluated graphically.

10.
Sensors (Basel) ; 23(6)2023 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-36991755

RESUMO

The exponentially growing concern of cyber-attacks on extremely dense underwater sensor networks (UWSNs) and the evolution of UWSNs digital threat landscape has brought novel research challenges and issues. Primarily, varied protocol evaluation under advanced persistent threats is now becoming indispensable yet very challenging. This research implements an active attack in the Adaptive Mobility of Courier Nodes in Threshold-optimized Depth-based Routing (AMCTD) protocol. A variety of attacker nodes were employed in diverse scenarios to thoroughly assess the performance of AMCTD protocol. The protocol was exhaustively evaluated both with and without active attacks with benchmark evaluation metrics such as end-to-end delay, throughput, transmission loss, number of active nodes and energy tax. The preliminary research findings show that active attack drastically lowers the AMCTD protocol's performance (i.e., active attack reduces the number of active nodes by up to 10%, reduces throughput by up to 6%, increases transmission loss by 7%, raises energy tax by 25%, and increases end-to-end delay by 20%).

11.
Lancet Psychiatry ; 10(4): 282-295, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36848914

RESUMO

Drug use is an increasing global public health concern. We reviewed the prevalence and patterns of drug use, drug use disorders, and the extent of treatment services in 21 countries and one territory in the Eastern Mediterranean region from 2010 to 2022. Online databases were systematically searched on April 17, 2022, along with other sources for grey literature. The extracted data were analysed and used for synthesis at the country, subregional, and regional levels. The prevalence of drug use is higher in the Eastern Mediterranean region than global estimates, with cannabis, opium, khat, and tramadol among the main drugs used in the region. Data on the prevalence of drug use disorders were scarce and heterogeneous. Treatment facilities for drug use disorders are available in most countries, but opioid agonist treatment exists in only seven countries. There is a need to expand evidence-based and cost-effective care. Limited data exist, especially regarding drug use disorders, treatment coverage, and drug use among women and young people.


Assuntos
Transtornos Relacionados ao Uso de Substâncias , Humanos , Feminino , Adolescente , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Região do Mediterrâneo/epidemiologia , Prevalência
12.
Front Pharmacol ; 13: 1008182, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36313367

RESUMO

The conventional chemical methods of nanoparticles synthesis have been effectively replaced by nanoparticle synthesis mediated by plants. The current study describes the environmental friendly synthesis of chromium oxide nanoparticles (Cr2O3 NPs) using Erythrophleum guineense plant extract. The synthesis of Cr2O3 NPs was validated by UV/VIS spectroscopy, Energy Dispersive X-Ray (EDX), Scanning Electron Microscopy (SEM), and X-ray diffraction (XRD) studies. The appearance of the Sharpe peak at 460 nm in the UV/Vis spectrum and the colour change caused by surface plasma resonance confirmed the formation of Cr2O3 NPs. The EDX spectrum of Cr2O3 nanoparticles revealed the presence of carbon, oxygen, and chromium, while SEM analysis revealed an irregular round morphology (with a size below 400 nm). In addition, XRD studies suggested their crystalline nature by the characteristic peaks at 34° and 36° and 42° (2Ɵ), respectively. The green synthesized Cr2O3 NPs showed promise as in-vitro cholinesterase inhibitor at tested concentrations (62.5-1,000 µg/ml), with IC50 values of 120 and 100 µg/ml against Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE), respectively. The results suggested that the green synthesized Cr2O3 NPs could be used in the future to stop enzyme from working and for other biological activities.

14.
Artigo em Inglês | MEDLINE | ID: mdl-35954669

RESUMO

This research aimed to (1) assess the extent to which mental health and psycho-social support (MHPSS) was included in the national response to the COVID-19 pandemic in African countries, and (2) explore barriers and enablers to MHPSS integration into the COVID-19 response. A mixed-methods study, using an online survey and in-depth interviews, was conducted. Participants included Mental Health Focal Points at the Ministries of Health, the World Health Organization (WHO) country and regional offices, and civil society representatives. Responses were received from 28 countries out of 55 contacted. The implementation level, based on standard guidelines, of MHPSS activities was below 50% in most countries. The most implemented MHPSS activities were establishing coordination groups (57%) and developing MHPSS strategy (45%), while the least implemented activities included implementing the developed MHPSS strategy (32%) and establishing monitoring and evaluation mechanisms (21%). Key factors that hindered implementing MHPSS activities included lack of political commitment and low prioritisation of mental health during emergencies, as it was seen as a "less important" issue during the COVID-19 pandemic, when more importance was given to infection prevention and control (IPC). However, there are signs of optimism, as mental health gained some attention during COVID-19. It is imperative to build on the attention gained by integrating MHPSS in emergency preparedness and response and strengthening mental health systems in the longer term.


Assuntos
COVID-19 , Saúde Mental , COVID-19/epidemiologia , Humanos , Pandemias , Sistemas de Apoio Psicossocial , Apoio Social
15.
Nanomaterials (Basel) ; 12(16)2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-36014601

RESUMO

The current article discusses the outcomes of the double diffusion convection of peristaltic transport in Sisko nanofluids along an asymmetric channel having an inclined magnetic field. Consideration is given to the Sisko fluid model, which can forecast both Newtonian and non-Newtonian fluid properties. Lubricating greases are the best examples of Sisko fluids. Experimental research shows that most realistic fluids, including human blood, paint, dirt, and other substances, correspond to Sisko's proposed definition of viscosity. Mathematical modelling is considered to explain the flow behavior. The simpler non-linear PEDs are deduced by using an elongated wavelength and a minimal Reynolds number. The expression is also numerically calculated. The impacts of the physical variables on the quantities of flow are plotted graphically as well as numerically. The results reveal that there is a remarkable increase in the concentration, temperature, and nanoparticle fraction with the rise in the Dufour and thermophoresis variables.

16.
East Mediterr Health J ; 28(5): 321-328, 2022 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-35670436

RESUMO

Background: Mental health has been identified by the World Health Organization as an integral component of the COVID-19 response. Aims: This study aimed to estimate the impact of COVID-19 pandemic on mental, neurological and substance use disorders (MNS) services in the Eastern Mediterranean Region. Methods: The assessment was conducted through a web-based survey that was completed by national mental health focal persons and was analysed between June and August 2020. Results: School and workplace mental health services were wholly or partially disrupted in more than 70% of reporting countries. Fewer than 20% of the countries in the Region reported full operations of mental health services for children and adolescents or for older adults. The main reasons were travel restrictions, decreases in inpatient volumes due to the cancellation of elective care, decreases in outpatient volumes due to patients not presenting, and health authority directives for the closure of outpatient services. The majority (85%) of countries responded by establishing MNS helplines using telemedicine/teletherapy and digital psychological interventions. The fragile and conflict-affected states relied mostly on implementing infection prevention and control measures at MNS service facilities. Gaps were identified in the areas of addictive behaviours, substance use and neurology research related to the pandemic. Conclusion: The assessment highlights the need to strengthen capacities for monitoring changes in service delivery and utilization, and documents evidence on what works in different settings during the different phases of the pandemic to facilitate informed decisions related to the nature and timing of adaptations to service delivery.


Assuntos
COVID-19 , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Idoso , Criança , Humanos , Saúde Mental , Pandemias/prevenção & controle , Sistemas de Apoio Psicossocial , SARS-CoV-2
17.
Nanomaterials (Basel) ; 12(7)2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35407168

RESUMO

The peristaltic propulsion of a Johnson-Segalman nanofluid under the dependency of a double-diffusion convection and induced magnetic field was investigated in this study. On the premise of continuity, linear momentum, solute concentration, thermal energy, and nanoparticle concentration, a flow issue was proposed. The lubrication methodology was used to carry out mathematical modelling. Numerical techniques were used to solve the corresponding highly nonlinear partial differential equations. The exact solution of concentration, temperature, and nanoparticle were computed. The manifestations of all relevant constraints were theoretically and graphically evaluated. The current study develops a theoretical model that can predict how various parameters affect the characteristics of blood-like fluid flows.

18.
Front Cardiovasc Med ; 9: 824601, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35224056

RESUMO

BACKGROUND: Vaccine-induced thrombotic thrombocytopenia (VITT) post SARS-CoV-2 vaccination is characterized by thrombocytopenia and severe thrombosis. Platelet function during patient recovery in the medium-/long-term has not been investigated fully. Here, we undertook a 3-month study, assessing the recovery of a VITT patient and assessing platelet morphology, granule content and dense-granule release at two distinct time points during recovery. CASE PRESENTATION: A 61 year-old female was admitted to hospital 15 days post ChAdOx1 nCov-19 vaccination. Hematological parameters and peripheral blood smears were monitored over 3 months. Platelet morphology and granule populations were assessed using transmission electron microscopy (TEM) at two distinct time points during recovery, as was agonist-induced platelet dense-granule release. Upon admission, the patient had reduced platelet counts, increased D-dimer and high anti-PF4 antibodies with multiple sites of cerebral venous sinus thrombosis (CVST). Peripheral blood smears revealed the presence of large, hypergranular platelets. Following treatment, hematological parameters returned to normal ranges over the study period. Anti-PF4 antibodies remained persistently high up to 90 days post-admission. Two days after admission, VITT platelets contained more granules per-platelet when compared to day 72 and healthy platelets. Additionally, maximal ATP release (marker of dense-granule release) was increased on day 2 compared to day 72 and healthy control platelets. CONCLUSION: This study highlights a previously unreported observation of platelet hypergranularity in VITT which may contribute to the thrombotic risk associated with VITT. Optimal approaches to monitoring recovery from VITT over time remains to be determined but our findings may help inform therapeutic decisions relating to anticoagulation treatment in this novel pathology.

19.
Am J Hematol ; 97(5): 562-573, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35132679

RESUMO

There are limited prospective data on lenalidomide, subcutaneous bortezomib, and dexamethasone (RsqVd) in transplant-eligible/transplant-ineligible patients with newly diagnosed multiple myeloma. Reliable biomarkers for efficacy and toxicity are required to better tailor therapy. Two parallel studies were conducted by Cancer Trials Ireland (CTI; NCT02219178) and the Dana-Farber Cancer Institute (DFCI; NCT02441686). Patients received four 21-day cycles of RsqVd and could then receive either another 4 cycles of RsqVd or undergo autologous stem cell transplant. Postinduction/posttransplant, patients received lenalidomide maintenance, with bortezomib included for high-risk patients. The primary endpoint was overall response rate (ORR) after 4 cycles of RsqVd. Eighty-eight patients were enrolled and 84 treated across the two studies; median age was 64.7 (CTI study) and 60.0 years (DFCI study), and 59% and 57% had stage II-III disease. Pooled ORR after 4 cycles in evaluable patients was 93.5%, including 48.1% complete or very good partial responses (CTI study: 91.9%, 59.5%; DFCI study: 95.0%, 37.5%), and in the all-treated population was 85.7% (44.0%). Patients received a median of 4 (CTI study) and 8 (DFCI study) RsqVd cycles; 60% and 31% of patients (CTI study) and 33% and 51% of patients (DFCI study) underwent transplant or received further RsqVd induction, respectively. The most common toxicity was peripheral neuropathy (pooled: 68%, 7% grade 3-4; CTI study: 57%, 7%; DFCI study: 79%, 7%). Proteomics analyses indicated elevated kallikrein-6 in good versus poor responders, decreased midkine in good responders, and elevated macrophage inflammatory protein 1-alpha in patients who stopped treatment from neurotoxicity, suggesting predictive biomarkers warranting further investigation.


Assuntos
Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/efeitos adversos , Dexametasona/efeitos adversos , Humanos , Quimioterapia de Indução , Lenalidomida/efeitos adversos , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Estudos Prospectivos
20.
Materials (Basel) ; 15(3)2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35160944

RESUMO

Additively manufactured composite specimens exhibit anisotropic properties, meaning that the elastic response changes with respect to orientation. Both in-plane and out-of-plane mechanical properties are important for designing purpose. Recent studies have characterised the in-plane performance. In this study, however, through-thickness tensile strength of 3D polymer composites were determined by printing of continuous carbon fibre reinforced thermoplastic polyamide-based composite, manufactured using a Markforged Two 3D printer. This paper discusses sample fabrication and geometry, adhesive used, and testing procedure. Test standards used to determine out-of-plane properties are tedious as most of the premature failures occur between the specimens and the tabs. Two types of samples were printed according to ASTM flatwise tension standard and the results were compared to determine the geometry effect on the interlaminar strength. This test method consists of subjecting the printed sample to a uniaxial tensile force normal to the plane. With this method, the acceptable failure modes for tensile strength must be internal to the structure, not between the sample and the end tabs. Micro-computed tomography (µCT) was carried out to observe the porosity. Surface behaviour was studied using scanning electron microscopy (SEM) to see the voids and the distribution of the fibres in the samples. The results showed consistent values for tensile strength and elastic modulus for Araldite glue after initial trials (with some other adhesives) to determine a suitable choice of adhesive for bonding the samples with the tabs. Circular specimens have higher tensile strength and elastic modulus as compared to rectangular specimens.

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