Sustainable release of propranolol hydrochloride laden with biconjugated-ufasomes chitosan hydrogel attenuates cisplatin-induced sciatic nerve damage in in vitro/in vivo evaluation

Peripheral nerve injuries significantly impact patients’ quality of life and poor functional recovery. Chitosan–ufasomes (CTS–UFAs) exhibit biomimetic features, making them a viable choice for developing novel transdermal delivery for neural repair. This study aimed to investigate the role of CTS–UFAs loaded with the propranolol HCl (PRO) as a model drug in enhancing sciatica in cisplatin-induced sciatic nerve damage in rats. Hence, PRO–UFAs were primed, embedding either span 20 or 60 together with oleic acid and cholesterol using a thin-film hydration process based on full factorial design (2(4)). The influence of formulation factors on UFAs’ physicochemical characteristics and the optimum formulation selection were investigated using Design-Expert(®) software. Based on the optimal UFA formulation, PRO–CTS–UFAs were constructed and characterized using transmission electron microscopy, stability studies, and ex vivo permeation. In vivo trials on rats with a sciatic nerve injury tested the efficacy of PRO–CTS–UFA and PRO–UFA transdermal hydrogels, PRO solution, compared to normal rats. Additionally, oxidative stress and specific apoptotic biomarkers were assessed, supported by a sciatic nerve histopathological study. PRO–UFAs and PRO–CTS–UFAs disclosed entrapment efficiency of 82.72 ± 2.33% and 85.32 ± 2.65%, a particle size of 317.22 ± 6.43 and 336.12 ± 4.9 nm, ζ potential of −62.06 ± 0.07 and 65.24 ± 0.10 mV, and accumulatively released 70.95 ± 8.14% and 64.03 ± 1.9% PRO within 6 h, respectively. Moreover, PRO–CTS–UFAs significantly restored sciatic nerve structure, inhibited the cisplatin-dependent increase in peripheral myelin 22 gene expression and MDA levels, and further re-established sciatic nerve GSH and CAT content. Furthermore, they elicited MBP re-expression, BCL-2 mild expression, and inhibited TNF-α expression. Briefly, our findings proposed that CTS–UFAs are promising to enhance PRO transdermal delivery to manage sciatic nerve damage

Optimization of Cobalt Nanoparticles for Biogas Enhancement from Green Algae Using Response Surface Methodology

Organic matter may be converted to energy through various methods, but the most preferable one is the Anaerobic Digestion (AD), specifically for biogas production. In sustainable bioenergy production, it can undoubtedly be called one of the most widely used methods from the various feedstock. Over the past years, algae waste has become an increasingly acute environmental problem but luckily it can be used as feedstock to produce bioenergy. In order to improve the energy productivity of green algae, this study is focused on the introduction of cobalt (Co) nanoparticles (NPs) in the AD process. The concentration of Co NPs was optimized using response surface methodology (RSM). Mesophilic temperature range (25–45 °C), initial pH (5–9) and Co NPs dosage (0.5–2 mg/L) were selected as the independent variables for RSM. The results indicated that at optimized values (Co NPs concentration = 1 mg/L, initial pH = 7, and digestion temperature = 35 °C) produced the highest biogas yield of 298 ml. An experiment was carried out at optimized conditions to explore the effect on biogas production. The results showed that Co NPs had a positive influence on biogas yield. The low concentrations achieved higher biogas production as compared to higher ones. A maximum biogas yield of 678 mL is achieved by Co NPs (1 mg/L). AD performance was further evaluated by the modified Gompertz model. Different kinetic parameters were calculated. The values of the performance indicators confirmed that the mathematical model fitted well with experimental data

Corneal nerve and brain imaging in mild cognitive impairment and dementia

Background: Visual rating of medial temporal lobe atrophy (MTA) is an accepted structural neuroimaging marker of Alzheimer's disease. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic technique that detects neuronal loss in peripheral and central neurodegenerative disorders. Objective: To determine the diagnostic accuracy of CCM for mild cognitive impairment (MCI) and dementia compared to medial temporal lobe atrophy (MTA) rating on MRI. Methods: Subjects aged 60-85 with no cognitive impairment (NCI), MCI, and dementia based on the ICD-10 criteria were recruited. Subjects underwent cognitive screening, CCM, and MTA rating on MRI. Results: 182 subjects with NCI (n = 36), MCI (n = 80), and dementia (n = 66), including AD (n = 19, 28.8%), VaD (n = 13, 19.7%), and mixed AD (n = 34, 51.5%) were studied. CCM showed a progressive reduction in corneal nerve fiber density (CNFD, fibers/mm2) (32.0±7.5 versus 24.5±9.6 and 20.8±9.3, p < 0.0001), branch density (CNBD, branches/mm2) (90.9±46.5 versus 59.3±35.7 and 53.9±38.7, p < 0.0001), and fiber length (CNFL, mm/mm2) (22.9±6.1 versus 17.2±6.5 and 15.8±7.4, p < 0.0001) in subjects with MCI and dementia compared to NCI. The area under the ROC curve (95% CI) for the diagnostic accuracy of CNFD, CNBD, CNFL compared to MTA-right and MTA-left for MCI was 78% (67-90%), 82% (72-92%), 86% (77-95%) versus 53% (36-69%) and 40% (25-55%), respectively, and for dementia it was 85% (76-94%), 84% (75-93%), 85% (76-94%) versus 86% (76-96%) and 82% (72-92%), respectively. Conclusion: The diagnostic accuracy of CCM, a non-invasive ophthalmic biomarker of neurodegeneration, was high and comparable with MTA rating for dementia but was superior to MTA rating for MCI

Family-based pediatric weight management interventions in US primary care settings targeting children ages 6-12 years old: A systematic review guided by the RE-AIM framework.

Obesity is a pandemic that disproportionately affects children from vulnerable populations in the USA. Current treatment approaches in primary care settings in the USA have been reported to be insufficient at managing pediatric obesity, primarily due to implementation challenges for healthcare systems and barriers for families. While the literature has examined the efficacy of pediatric obesity interventions focused on internal validity, it lacks sufficient reporting and analysis of external validity necessary for successful translation to primary care settings. We conducted a systematic review of the primary-care-setting literature from January 2007 to March 2020 on family-based pediatric weight management interventions in both English and/or Spanish for children ages 6-12 years in the USA using the Reach, Efficacy/Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. A literature search, using PRISMA guidelines, was conducted in January 2022 using the following electronic databases: Medline Ovid, Embase, and Cochrane Library. 22 270 records were screened, and 376 articles were reviewed in full. 184 studies were included. The most commonly reported dimensions of the RE-AIM framework were Reach (65%), Efficacy/Effectiveness (64%), and Adoption (64%), while Implementation (47%) and Maintenance (42%) were less often reported. The prevalence of reporting RE-AIM construct indicators ranged greatly, from 1% to 100%. This systematic review underscores the need for more focus on external validity to guide the development, implementation, and dissemination of future pediatric obesity interventions based in primary care settings. It also suggests conducting additional research on sustainable financing for pediatric obesity interventions

Association of Cerebral Ischemia With Corneal Nerve Loss and Brain Atrophy in MCI and Dementia

IntroductionThis study assessed the association of cerebral ischemia with neurodegeneration in mild cognitive impairment (MCI) and dementia.MethodsSubjects with MCI, dementia and controls underwent assessment of cognitive function, severity of brain ischemia, MRI brain volumetry and corneal confocal microscopy.ResultsOf 63 subjects with MCI (n = 44) and dementia (n = 19), 11 had no ischemia, 32 had subcortical ischemia and 20 had both subcortical and cortical ischemia. Brain volume and corneal nerve measures were comparable between subjects with subcortical ischemia and no ischemia. However, subjects with subcortical and cortical ischemia had a lower hippocampal volume (P &lt; 0.01), corneal nerve fiber length (P &lt; 0.05) and larger ventricular volume (P &lt; 0.05) compared to those with subcortical ischemia and lower corneal nerve fiber density (P &lt; 0.05) compared to those without ischemia.DiscussionCerebral ischemia was associated with cognitive impairment, brain atrophy and corneal nerve loss in MCI and dementia

Two prolonged viremic SARS-CoV-2 infections with conserved viral genome for two months.

We document two cases of viremic and prolonged active infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) where the viral genome was conserved for two months, but infection was with little or no symptoms. The first infection persisted for 80 days and the second for 62 days. Clearance of infection occurred 40 and 41 days, respectively, after development of detectable antibodies. Both cases were identified incidentally in an investigation of reinfection in a cohort of 133,266 laboratory-confirmed infected persons

Assessment of the Risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Reinfection in an Intense Reexposure Setting.

BACKGROUND: Risk of reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We assessed the risk and incidence rate of documented SARS-CoV-2 reinfection in a cohort of laboratory-confirmed cases in Qatar. METHODS: All SARS-CoV-2 laboratory-confirmed cases with at least 1 polymerase chain reaction-positive swab that was ≥45 days after a first positive swab were individually investigated for evidence of reinfection. Viral genome sequencing of the paired first positive and reinfection viral specimens was conducted to confirm reinfection. RESULTS: Out of 133 266 laboratory-confirmed SARS-CoV-2 cases, 243 persons (0.18%) had at least 1 subsequent positive swab ≥45 days after the first positive swab. Of these, 54 cases (22.2%) had strong or good evidence for reinfection. Median time between the first swab and reinfection swab was 64.5 days (range, 45-129). Twenty-three of the 54 cases (42.6%) were diagnosed at a health facility, suggesting presence of symptoms, while 31 (57.4%) were identified incidentally through random testing campaigns/surveys or contact tracing. Only 1 person was hospitalized at the time of reinfection but was discharged the next day. No deaths were recorded. Viral genome sequencing confirmed 4 reinfections of 12 cases with available genetic evidence. Reinfection risk was estimated at 0.02% (95% confidence interval [CI], .01%-.02%), and reinfection incidence rate was 0.36 (95% CI, .28-.47) per 10 000 person-weeks. CONCLUSIONS: SARS-CoV-2 reinfection can occur but is a rare phenomenon suggestive of protective immunity against reinfection that lasts for at least a few months post primary infection

SARS-CoV-2 antibody-positivity protects against reinfection for at least seven months with 95% efficacy.

BACKGROUND: Reinfection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been documented, raising public health concerns. SARS-CoV-2 reinfections were assessed in a cohort of antibody-positive persons in Qatar. METHODS: All SARS-CoV-2 antibody-positive persons from April 16 to December 31, 2020 with a PCR-positive swab ≥14 days after the first-positive antibody test were investigated for evidence of reinfection. Viral genome sequencing was conducted for paired viral specimens to confirm reinfection. Incidence of reinfection was compared to incidence of infection in the complement cohort of those who were antibody-negative. FINDINGS: Among 43,044 antibody-positive persons who were followed for a median of 16.3 weeks (range: 0-34.6), 314 individuals (0.7%) had at least one PCR positive swab ≥14 days after the first-positive antibody test. Of these individuals, 129 (41.1%) had supporting epidemiological evidence for reinfection. Reinfection was next investigated using viral genome sequencing. Applying the viral-genome-sequencing confirmation rate, the incidence rate of reinfection was estimated at 0.66 per 10,000 person-weeks (95% CI: 0.56-0.78). Incidence rate of reinfection versus month of follow-up did not show any evidence of waning of immunity for over seven months of follow-up. Meanwhile, in the complement cohort of 149,923 antibody-negative persons followed for a median of 17.0 weeks (range: 0-45.6), incidence rate of infection was estimated at 13.69 per 10,000 person-weeks (95% CI: 13.22-14.14). Efficacy of natural infection against reinfection was estimated at 95.2% (95% CI: 94.1-96.0%). Reinfections were less severe than primary infections. Only one reinfection was severe, two were moderate, and none were critical or fatal. Most reinfections (66.7%) were diagnosed incidentally through random or routine testing, or through contact tracing. INTERPRETATION: Reinfection is rare in the young and international population of Qatar. Natural infection appears to elicit strong protection against reinfection with an efficacy ~95% for at least seven months. FUNDING: Biomedical Research Program, the Biostatistics, Epidemiology, and Biomathematics Research Core, and the Genomics Core, all at Weill Cornell Medicine-Qatar, the Ministry of Public Health, Hamad Medical Corporation, and the Qatar Genome Programme

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Expired EBT3 Films&rsquo; Sensitivity for the Measurement of X-ray and UV Radiation: An Optical Analysis

The aim of this study is to compare the optical responses of external beam therapy 3 (EBT3) films exposed to X-rays and solar ultraviolet rays (SUV-rays), as a dose control technique in the clinical sector for various radiation types, energies, and absorbed doses up to 4 Gy. In this study, EBT3 films with three different expiry dates were prepared and cut into pieces of size 2 by 2 cm2. The first group was exposed to 90 kVp X-rays, while the second group was exposed to the SUV-rays at noon. The analysis was performed using a visible Jaz spectrometer and an EPSON Perfection V370 Photo scanner to obtain the absorbance, the net reflective optical density (ROD) and the red-green-blue (RGB) values of the samples. The results have shown that spectroscopic measurements of the exposed expired EBT3 films with these radiation sources are able to produce primary peaks and secondary peaks at &lambda; = 641.74 nm and &lambda; = 585.98 nm for X-rays, and at &lambda; = 637.93 nm and &lambda; = 584.45 nm for SUV-rays, respectively. According to these findings, compared to 2021 films that expired shortly before the trial start date; 2018 films responded better to the absorbed dose than 2016 films when exposed to both X-ray and SUV-rays. In terms of energy dependence, the expired EBT3 2018 had the largest net ROD value. Using L*a*b* indices extracted from the RGB data, and despite that EBT3 films have expiry dates according to the manufacturer; all the films exhibited a substantial colour change, indicating that these films are still usable for clinical and research purposes