Combined chemo-magnetic field-photothermal breast cancer therapy based on porous magnetite nanospheres

The efficacy of different modalities of treating breast cancer is inhibited by several limitations such as off-targeted drug distribution, rapid drug clearance, and drug resistance. To overcome these limitations, we developed Lf-Doxo-PMNSs for combined chemo-MF-PTT. The PMNSs were synthesized by hydrothermal method and their physicochemical properties were examined by FE-SEM, TEM, DLS, TGA, XRD investigations. The cytotoxicity of as-synthesized NPs against 4T1 cells was carried out by MTT and flow cytometry assays. Afterwards, the anti-cancer activities of as-synthesized Lf-Doxo-PMNSs on the tumor status, drug distribution and apoptosis mechanism were evaluated. The anti-cancer assays showed that Lf-Doxo-PMNSs significantly suppressed the cancer cell proliferation and tumor weight by prolonging drug availability and potential drug loading in tumor cells; whereas they showed a minimum cytotoxicity against non-cancerous cells. Likewise, combined chemo-MF-PTT using Lf-Doxo-PMNSs displayed the highest anti-cancer activity followed by combined chemo-PTT and combined chemo-MF therapy based on altering the apoptosis mechanism. Therefore, these results showed that combined chemo-MF-PTT based on Lf-Doxo-PMNSs can be used as a promising therapeutic platform with potential targeted drug delivery and high loading capacity features as well as reducing cancer drug resistance

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND: Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. METHODS: We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. FINDINGS: Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. INTERPRETATION: As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Clinical Outcome of HIV Infected Patients Receiving Antiretroviral Therapy with Immunologic-Virologic Discordance (2012-2016)

Background: The aim of present study was to investigate the Consequence of Immunologic and Virologic Discordancy and its associated factors in people living with HIV (PLWH) receiving antiretroviral therapy (ART). Methods: In this retrospective cohort study, case records of all HIV positive patients from 2012 were evaluated. Viral response less than 400 copies/mL defined positive for at least 6 months after treatment initiation and immunologic response considered acceptable when patient experienced a rise of more than 50 CD4 (cells/μL) one year after the treatment onset. The status of viral load and CD4 count was recorded, and the state of matching or discordance of the virologic and immunologic responses were determined. Results: In the present survey, 339 patients were examined, the most ART regimen in the patients faced Immunologic -Virologic Discordance (IVD) was Atripla (Emtricitabine plus Tenofovir and Efavirenz) (59.4%), and then respectively Cobavir (Lamivudine plus Zidovudine) plus Efavirenz (25%), Cobavir plus Kaletra (Lopinavir plus Ritonavir) (12.5%) and Tenofovir plus Emtricitabine with Efavirenz (3.1%). The investigation of virologic response based on the patients gender, revealed that the rate of virologic response was approximately the same among male (97.1%) and female (97.6%) patients (P = 0.76). The investigation of HCV infection prevalence among patients revealed that 76 (22.8%) of patients was HCV positive and 257 (77.2%) was HCV negative. The prevalence of HCV among males (34%) was higher than female patients (4.7%). The prevalence of HBV infection was 3.4% in the males and 0.8% in the females (P = 0.13). Eight patients were HBV positive while 325 were negative. The CD4 measured in second year for male and female patients separately and the result revealed that it was more than 200 cells/μL in 168 cases containing 98 (73.3%) men and 70 (80.5%) women (P = 0.25). The investigation of opportunistic infections based on gender showed that 7 (3.4%) men and 3 (2.4%) women faced such infections (P = 0.59). Generally, 10(3.0%) patients faced opportunistic infections during the study. Of these, six (1.8%) patients had positive virologic response and four (44.4%) patients had negative virologic response (P < 0.001). Conclusion: In the present study, regarding the fact that the IVD and CD4 below 100 cells/μL showed a significant relation, the faster identification of PLWH and suitable treatment would reduce the risk of IVD. The IVD rate was higher in HCV positive patients, which should be evaluated earlier and receive an efficient regimen as soon as possible if they need treatment. Regarding the association between the consumption of Cobavir and IVD incidence, it is recommended to revise the ART regimens containing Cobavir