Protracted Duration Research Articles

Arrested tectonic development: Preservation of high-temperature fabrics in the sinistral Caiçara shear zone (Borborema province, northeastern Brazil)

The protracted duration of shearing in large-scale shear zones and/or their reactivation may obscure the metamorphic conditions under which the mylonites initially formed. Here, we describe the case of the high-temperature Caiçara shear zone (Borborema Province, northeastern Brazil), which shows only limited overprint by low temperature fabrics. The NE-trending Caiçara shear zone is ∼35 km long and comprises a 2 to 5 km-wide mylonitic belt. The shear zone was characterized by using kinematic analysis, including field and microstructural observations and measurement of quartz c-axis. The mylonitic foliation is steeply NW-dipping and contains a shallowly SW-plunging stretching lineation. Kinematic criteria (e.g., asymmetric porphyroclasts, S–C fabrics, asymmetric folds, C′-type shear bands) are consistent with sinistral shear. The dominant microstructures (e.g., chessboard extinction in quartz, grain boundary migration and subgrain rotation recrystallization in quartz, and polygonal aggregates of feldspar around porphyroclasts) and application of the opening angle thermometer indicate deformation dominantly at temperatures higher than ∼ 600 °C. In contrast to the common situation in the central Borborema Province, the Caiçara shear zone is unconnected to other shear zones. We attribute preservation of high-T fabrics to cessation of shearing in an early stage of development, preventing continuous fabric development at decreasing temperature conditions.

Optimizing Status Epilepticus Management in the Emergency Department: It's About Time.

Status epilepticus (SE) is a frequent medical emergency that requires expedited treatment to avoid the ensuing high incidence of morbidity and mortality associated with prolonged seizures. Protracted seizure duration itself has the potential to result in maladaptive neuronal responses that can not only further increase seizure duration and worsen clinical outcomes but also lead to reduced responsiveness to pharmacotherapy. Benzodiazepines are consistently recommended as first-line treatment due to their rapid onset and efficacy in terminating seizures, followed by the emergent administration of an antiepileptic drug (AED). Various benzodiazepine and AED options are recommended and can be utilized in this setting, all with their own unique advantages and challenges. With time at a premium, agents should be selected that can be rapidly administered and have an advantageous pharmacokinetic profile in order to limit seizure duration and optimize outcomes. The intent of this review is to provide an outline of the importance of time-to-treatment implementation in this setting, assess the landscape of options that may provide timing advantages, and examine potential strategies for deploying expeditious therapy.

Comparative Study on Physical Activity in Diabetic and Non-Diabetic Individuals and Influential Factors - China, 2020-2021.

The majority of Chinese patients with diabetes failed to achieve the level of physical activity recommended by clinical guidelines. The prevalence of low-level physical activity was found to be greater in individuals diagnosed with diabetes. It was observed that patients with a protracted duration of diabetes demonstrated a propensity to participate in lower levels of physical activity compared to those with a shorter disease trajectory. The likelihood of engaging in low-level physical activity associated with diabetes was higher in rural inhabitants, those with medium-tier education, employed individuals, and individuals who had longer sleep durations. Developing strategies and interventions to encourage greater involvement of Chinese diabetic patients in physical activity is essential. However, these strategies must take population characteristics into account.

Continuous assessment of ventricular fibrillation prognostic status during CPR: Implications for resuscitation

BackgroundVentricular fibrillation (VF) waveform measures reflect myocardial physiologic status. Continuous assessment of VF prognosis using such measures could guide resuscitation, but has not been possible due to CPR artifact in the ECG. A recently-validated VF measure (termed VitalityScore), which estimates the probability (0–100%) of return-of-rhythm (ROR) after shock, can assess VF during CPR, suggesting potential for continuous application during resuscitation. ObjectiveWe evaluated VF using VitalityScore to characterize VF prognostic status continuously during resuscitation. MethodsWe characterized VF using VitalityScore during 60 seconds of CPR and 10 seconds of subsequent pre-shock CPR interruption in patients with out-of-hospital VF arrest. VitalityScore utility was quantified using area under the receiver operating characteristic curve (AUC). VitalityScore trends over time were estimated using mixed-effects models, and associations between trends and ROR were evaluated using logistic models. A sensitivity analysis characterized VF during protracted (100-second) periods of CPR. ResultsWe evaluated 724 VF episodes among 434 patients. After an initial decline from 0–8 seconds following VF onset, VitalityScore increased slightly during CPR from 8–60 seconds (slope: 0.18%/min). During the first 10 seconds of subsequent pre-shock CPR interruption, VitalityScore declined (slope: −14%/min). VitalityScore predicted ROR throughout CPR with AUCs 0.73–0.75. Individual VitalityScore trends during 8–60 seconds of CPR were marginally associated with subsequent ROR (adjusted odds ratio for interquartile slope change (OR) = 1.10, p = 0.21), and became significant with protracted (100 seconds) CPR duration (OR = 1.28, p = 0.006). ConclusionVF prognostic status can be continuously evaluated during resuscitation, a development that could translate to patient-specific resuscitation strategies.

A Comprehensive Review on Sustained Release Matrix Drug Delivery System

Formulations for sustained medication release are very useful in the treatment of chronic disorders. The oral route has selected matrix tablets as the most likely type of prolonged drug release. In order to generate therapeutic activity for a protracted duration, matrix tablets maintain a stable plasma drug concentration and sustain the rate of release of the drug throughout time. In preparations with a short half-life and high dosage frequency, extended-release is crucial. The matrix regulates how quickly the medication is released. Retardants such polyglycolic acid, polymethyl methacrylate, and hydroxypropyl methylcellulose (HPMC) are used. The retardant's matrix core contains the medication. The matrices employed can be mineral-based, hydrophobic, or biodegradable. Drug release is regulated in matrix tablets that can be made using wet granulation or direct compression techniques by the use of various kinds of polymers. Drug release from matrix tablets is controlled by both diffusion- and dissolution-controlled process. As a result, matrix tablets increase therapeutic efficacy while reducing the frequency of drug administration and increasing patient compliance.
 Keywords: Sustained release, Matrix Tablets, HPMC, Retardants, Biodegradable

In Loving Memory

<h3>Introduction/Background</h3> Adamantinoma is a rare primary low-grade malignant tum­­­­­­our of the appendicular skeleton. It primarily affects the long bones and is most commonly found in the tibia. The disease process has an indolent course and histogenic origin has not been clearly defined, however there have been several suggestions pertaining to a vascular origin in the literature. Local recurrences and lung metastases occur over a protracted duration. Less frequently, they have also been reported elsewhere; including four documented cases of soft tissue and five of pelvic bony adamantinoma. There is only one documented case of adamantinoma of the ovary and one of concurrent unrelated primary tumour. There are also no reports available regarding surgical management of a retroperitoneal adamantinoma of the pelvis within a gynaecological oncology surgical setting. Clinical guidelines have not yet been established. <h3>Results</h3> We present the case of a 65-year-old female with known recurrent and metastatic right tibial disease. On further investigation, a Positron Emission Tomography scan identified a primary breast lesion and an 11 cm mass in the right iliac fossa of suspected ovarian malignancy amenable to surgical resection (figure A). The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy and resection of a retroperitoneal mass arising from the pelvic sidewall encompassing the iliac vasculature. The tumour was cleaved from the external iliac artery successfully, however the external iliac vein perforated during dissection. A Satinsky clamp was placed and a small cuff of vein wall was removed alongside adherent tumour. The vein defect was closed with 5–0 prolene, ensuring a patent lumen (figure B). The patient made an uneventful recovery with histology confirming metastatic disease. <h3>Conclusion</h3> We present an overview of adamantinoma and highlight a previously undocumented gynaecological oncology surgical approach to this novel location of metastatic disease mimicking possible ovarian malignancy. We further explore disease histogenesis and also comment on an incidental finding or primary breast cancer. Particularly in uncommon locations, its heterogeneous nature presents radiological and histological challenges regarding diagnosis and treatment. Such cases warrant a full complement of MDT specialist knowledge and expertise; with advanced surgical skills and experience regarding retroperitoneal and pelvic sidewall anatomy. We also highlight a paucity of recommendations for surveillance and follow up and propose an individualised approach. We report on this unusual case to assist clinicians in the building of a consensus opinion for optimal adamantinoma case management under current circumstances where formal guidelines do not exist. <h3>Disclosures</h3> None

Radiological hazard assessment and sensitivity analysis for soil samples in Taghdoua area of Ranyah, Saudi Arabia

In this study, twenty-two samples of soil were studied for 222Rn, 226Ra, 232Th and 40K using hyper-pure Germanium (HPGe) detector. The soil samples were collected from an inhabited area surrounding the small mountain in Taghdoua area of Ranyah. The measured activity concentrations of 226Ra, 232Th and 40K in the soil were found to vary from 6 to 54, 7 to 52 and 299–761 Bq kg−1, respectively. The radiological risk parameters including excess lifetime cancer risks and other relevant parameters were also evaluated. Furthermore, the effect of ventilation changes on both external and internal doses over a protracted exposure duration were studied through sensitivity analysis using RESRAD-BUILD computer code. The external doses were observed to be insensitive to ventilation while a considerable change was detected in the internal doses with ventilation. Hence, the investigated radiological risk parameters including the results from RESRAD were all below the recommended limit.

Practical procedures for the delivery room resuscitation of micropreemies

There are no standardized procedures for the resuscitation of micropreemies but respiratory and circulatory stabilization immediately after birth should be prioritized. Without aggressive support by positive pressure ventilation, establishing effective respiration among micropreemies is not possible. The first step in postnatal stabilization is initiated by positive airway pressure with a bag and mask. Once the heart rate increases above 100 beats/m, intratracheal intubation should be achieved because it is unusual for a micropreemie to breathe spontaneously or by non-invasive respiratory support for a protracted duration. Until further information is available, initial FiO2 should be between 0.3 and 0.6, and titrated to achieve SpO2 obtained from healthy term infants for the first 10 min of life. Temperature control of infants is also critical for successful resuscitation and heat-loss minimizing procedures should be used e.g. with insulating bags. After securing the intratracheal tube, the infants should be transferred to the NICU for further procedures, including pulmonary surfactant installation and umbilical cord catheterization. Procedures in a delivery room under a radiant warmer should be limited to the initial resuscitation. In NICUs, the infants should be placed into a closed incubator to maintain high environmental temperature and humidity as well as decrease exposure to intervention and noise. Increased number of staff will also be needed to stabilize the infants further in the NICU. Finally, appropriate equipment (e.g. appropriate sized laryngoscopes) should be made readily available, along with regular practical training and education, whether in person or through SIM courses which are essential for all staff to achieve competence in successful resuscitation of the newborn micropreemie.

Generation of crystal-rich rhyodacites by fluid-induced crystal-mush rejuvenation: Perspective from the Late Triassic Nageng (sub-)volcanic complex of the East Kunlun Orogen, NW China

Remobilization of upper crustal crystal-rich magma reservoirs (“crystal mush”) following melt extraction has been widely invoked in the formation of crystal-rich erupted products. However, the melt storage duration and conditions, and the pre-eruptive magma chamber processes remain poorly understood. Here, we present new whole-rock elemental and Sr-Nd-Pb isotope data, and zircon U-Pb-Hf isotope and trace element data of the Nageng (sub-)volcanic complex in the East Kunlun Orogen of NW China. This complex consists of the highly-evolved (high SiO2, Rb/Sr) crystal-poor rhyolite and less-evolved crystal-rich rhyodacite and dacite porphyry. These rock types are genetically linked, based on their similar chondrite-normalized REE patterns and NdHf isotopes, and their linear correlation trends of 208Pb/204Pb and 207Pb/204Pb vs. 206Pb/204Pb. Their depleted whole-rock εNd(t) (−9.74 to −7.37) and zircon εHf(t) (−7.16 to −3.48) values, together with their Proterozoic two-stage Hf model ages (1707–1474 Ma), are indicative of an ancient lower crustal magma source. The overlapping zircon ages but distinct composition (74–80 vs. 60–66 wt% SiO2) and crystallinity (~5 vs. 30–40 vol%) between the crystal-poor rhyolite and dacite porphyry can be explained by melt extraction from the crystal mush zone. The lack of resorption texture and large age interval (~8 Myr) between the zircon core (ca. 228 Ma) and rim (ca. 220 Ma) indicate that the crystal mush remained partially molten for protracted duration. The melt storage condition was constrained by Ti-in-zircon thermometry to be low-temperature, around the granitic solidus (650–700 °C). The crystal-rich nature and slightly negative Eu anomalies suggest that the dacite porphyry was formed in the roof zone (solidification front) of the crystal mush. The occurrence of resorbed zircon core (ca. 220 Ma) overgrown by much younger rim (ca. 213 Ma) for the crystal-rich rhyodacite demonstrates long-term rejuvenation of a semi-solidified crystal mush. The similar zircon core-rim Ti contents and Th/U, Yb/Gd, Zr/Hf ratios preclude that the crystal mush was rejuvenated by hotter, more mafic magmas. However, the widespread fluorite-rich magmatic-hydrothermal veining, combined with the reduced nature (indicated by the zircon Ce4+/Ce3+ drop from core to rim) of the crystal-rich rhyodacite, imply that the volatile-rich fluid influx may have been important in reactivating the crystal-mush for later crystal-rich rhyodacite eruption.

Preventing facial pressure injuries among health care staff working in diverse COVID-19 care environments.

The aim of this study was to determine the impact of a specially designed care bundle on the development of facial pressure injuries among frontline health care workers wearing personal protective equipment (PPE) during the COVID‐19 pandemic. This was a mixed methods study. First, a pre‐posttest observational design was employed to evaluate the impact of the pre‐piloted intervention, a care bundle including skin cleansing and hydration, protective material use, facemask selection and skin inspection, developed in line with international best practice guidelines. Data were collected using survey methodology. Frontline COVID‐19 staff working in acute, community and ambulance services were invited to participate. Then, judgemental and volunteer sampling was used to select participants to undertake semi‐structured interviews to elicit feedback on their perceptions of the care bundle. The sample included 120 acute hospital staff, 60 Ambulance staff, 24 Community Hub staff and 20 COVID‐19 testing centre staff. A survey response rate of 61% was realised (n = 135/224). Of the participants, 32% (n = 43) had a facial pressure ulcer (FPI) pre‐intervention and 13% (n = 18) developed an FPI while using the care bundle. The odds ratio (OR) was 0.33 (95% CI: 0.18 to 0.61; P = .0004), indicating a 77% reduction in the odds of FPI development with use of the care bundle. Analysis of the qualitative data from 22 interviews identified three key themes, the context for the care bundle, the ease of use of the care bundle and the care bundle as a solution to FPI development. The care bundle reduced the incidence of FPI among the participants and was found to be easy to use. Implementation of skin protection for frontline staff continues to be important given the persistently high incidence of COVID‐19 and the ongoing need to wear PPE for protracted durations.

Xenon isotope constraints on ancient Martian atmospheric escape

Trapped, paleoatmospheric xenon (Xe) in the Martian regolith breccia NWA 11220 is mass-dependently fractionated relative to solar Xe by 16.2 ± 2.7‰/amu. These data indicate that fractionation of atmospheric Xe persisted for hundreds of millions of years after planetary formation. Such a protracted duration of atmospheric Xe mass fractionation, which is particularly striking when compared to the non-fractionated state of Martian atmospheric krypton (Kr), cannot be easily reconciled with Xe escape as a neutral atom in a neutral hydrodynamic hydrogen wind. However, Xe escape as an ion coupled to a partially ionized hydrogen or oxygen wind provides a simple solution to problems associated with the neutral escape hypothesis. Ionic Xe escape requires a sufficiently high escape flux of a carrier ion (H+ or O+) and probably requires a structured planetary magnetic field to channel the flow. The end of Xe escape from Mars could be attributed to waning hydrogen sources from volcanic outgassing or from interactions of reduced impactors with surface water and ice. Alternatively, if Xe ions were driven off by O+, the end of Xe escape could be attributed to the decay of solar extreme ultra-violet radiation.

Theorising human trafficking through slow violence

Human trafficking is predominantly framed as a criminal justice issue with sensationalised, highly visible violence. Stereotypical figures of young women in danger, passively poised to be rescued by figures of the state or vigilante justice, animate public discourse and policy. Yet the reality of trafficking is often far more complex than the linear narratives presented in the mainstream. In this article, I argue that human trafficking is more readily accessible as slow violence, the accumulation and accretion of the consequences of systematic oppression over time. I use Nixon's Slow Violence and the Environmentalism of the Poor to articulate a stance against the flash of trafficking's ‘master narratives’. Slow violence offers three key elements for theorising human trafficking, i.e. that the harms are so gradual or delayed they: become imperceptible; compound over protracted durations of time; and may be so mundane and unspectacular to not even register as ‘violence’ in our vernacular. Aligned with a critical trafficking studies approach that draws attention to power dynamics and imbalances, slow violence focuses on the forms of exploitation and precarity that are taken for granted or assumed to be static. I use a collection of artifacts and examples from dominant anti-trafficking organisations and media to demonstrate the urgency required to both rethink trafficking against these flattening overgeneralisations and recommit to a transformative practice that makes more lives liveable. In the tradition of feminist anti-violence scholarship, I conclude by shifting from the micro-level examples of trafficking that fuel misinformation campaigns to the systems that perpetuate violence, exploitation and extraction – and must be eradicated if we are committed to ending human trafficking locally and globally.

Comparison and Evaluation of Different Radiotherapy Techniques Using Biodosimetry Based on Cytogenetics.

Simple SummaryCell killing and tumor response in cancer patients depends not only on the absorbed radiation dose but also on the dose rate and delivery time. In this study, a biodosimetry assay based on the frequency of dicentrics chromosomes scored in peripheral blood lymphocytes from prostate cancer patients and PC3 human prostate cancer cell line was used to investigate the radiobiological impact of the relative prolonged dose delivery time and/or decreased dose rate met in advanced modulated radiotherapy techniques (VMAT and IMRT) compared to conventional non-modulated (3D-CRT) in prostate patient plan irradiations. The results showed a small but statistically significant decrease in the number of dicentrics following radiation with the modulated techniques, suggesting a corresponding decrease on the radiation dose efficiency. The biodosimetry assay could be used as an alternative to the laborious conventional clonogenic assay, while both lymphocytes and cancer cell line could effectively be used for estimation of the biological absorbed dose.While rapid technological advances in radiotherapy techniques have led to a more precise delivery of radiation dose and to a decreased risk of side effects, there is still a need to evaluate the efficacy of the new techniques estimating the biological dose and to investigate the radiobiological impact of the protracted radiotherapy treatment duration. The aim of this study is to compare, at a cytogenetic level, advanced radiotherapy techniques VMAT and IMRT with the conventional 3D-CRT, using biological dosimetry. A dicentric biodosimetry assay based on the frequency of dicentrics chromosomes scored in peripheral blood lymphocytes from prostate cancer patients and PC3 human prostate cancer cell line was used. For each patient blood sample and each subpopulation of the cultured cell line, three different irradiations were performed using the 3D-CRT, IMRT, and VMAT technique. The absorbed dose was estimated with the biodosimetry method based on the induced dicentric chromosomes. The results showed a statistically significant underestimation of the biological absorbed dose of ~6% for the IMRT and VMAT compared to 3D-CRT irradiations for peripheral blood lymphocytes, whereas IMRT and VMAT results were comparable without a statistically significant difference, although slightly lower values were observed for VMAT compared to IMRT irradiation. Similar results were obtained using the PC3 cell line. The observed biological dose underestimation could be associated with the relative decreased dose rate and increase irradiation time met in modulated techniques compared to the conventional 3D-CRT irradiations.

A Retrospective Study on Spinal Dissemination of Supratentorial Glioma.

ObjectiveMetastatic spinal dissemination (MSD) of supratentorial glioma is very rare and there is no established standard of care. The current study investigates the clinical characteristics and course of spinal dissemination of supratentorial glioma.MethodsA retrospective analysis of adult patients with MSD of supratentorial glioma treated in the Department of Oncology in Beijing Shijitan Hospital, Capital Medical University from June 2012 until August 2021 was performed. The time to event was estimated using Kaplan–Meier analysis. Univariate analyses were performed using log-rank test and multivariate analysis was performed using the Cox proportional hazards model.ResultsThirty-four adult patients with MSD of supratentorial glioma were enrolled in this retrospective study. The median time to MSD (TTMSD) and overall survival (OS) were 5 months (range: 0–78 months) and 15 months (range: 0.7–85 months), respectively, in the entire cohort. Univariate analysis demonstrated that the patients who had received TMZ therapy had a longer TTMSD than those who did not (mTTMSD: 15 vs. 3 months, log-rank P = 0.0004). Furthermore, a protracted duration of salvage chemotherapy of >6 months after MSD was associated with longer OS of the patients with MSD of supratentorial glioma (mOS: 13 vs. 5 months, log-rank P = 0.0163) and reduced the death risk by 64.3% (hazard ratio: 0.357, 95% CI: 0.141–0.901, P = 0.029) compared with a duration ≤6 months.ConclusionPatients with MSD of supratentorial glioma experienced poor prognosis and adjuvant chemotherapy may delay the occurrence of MSD. The protracted duration of systemic salvage chemotherapy may favor survival after spinal dissemination.

A Comprehensive, Multimodal, Interdisciplinary Approach to Chronic Non-Cancer Pain Management in a Family Medicine Clinic: A Retrospective Cohort Review.

The complexity of chronic non-cancer pain in the setting of regulatory efforts to curb opioid usage presents a novel challenge for the medical community. Much of this burden falls on primary care clinics. We retrospectively quantified the reduction of opioid usage by patients in a multimodal, interdisciplinary, primary care clinic for chronic pain. A multimodal, interdisciplinary, chronic pain clinic embedded in a large academic military family medicine clinic operated one-half day weekly to address referrals from within the clinic at large. Appointment times were longer than typical primary care appointments. The clinic was equipped with support staff, ancillary specialty providers, and non-pharmacologic complementary treatment resources. A retrospective cohort review was conducted on 78 patients referred to this clinic from March 1, 2015 (the inception date of the clinic) through December 31, 2015. Fifty-four of 78 patients met inclusion criteria. Overall mean morphine equivalent daily dosing (MEDD) dropped from 31.5 MEDD to 20.5 MEDD (p = 0.0005) 12 months post-intervention and from 31.5 MEDD to 9.5 MEDD (p < 0.0001) 36 months post-intervention. Four patients with a high mean baseline opioid dose of 185.2 MEDD dropped to 29.9 MEDD 36 months post-intervention. The mean 0-10 pain score decreased from 5.3 ± 2.2 to 4.0 ± 2.5 (p = 0.001). A multimodal, interdisciplinary, primary care-based, chronic pain clinic equipped with extended appointment times, non-pharmacologic treatment resources, and specialty access can curb opioid usage. Leadership support for protracted appointment duration, complementary treatment resources, and interdisciplinary personnel is crucial to success.

Monitoring work and training load in military settings – what’s in the toolbox?

ABSTRACT Military personnel are required to complete physically demanding tasks when performing work and training, which may be quantified through the physical stress imposed (external load) or the resultant physiological strain (internal load). The aim of this narrative review is to provide an overview of the techniques used to monitor work and training load in military settings, summarise key findings, and discuss important practical, analytical, and conceptual considerations. Most investigations have focused upon measuring external and internal load in military training environments; however, limited data exist in operational settings. Accelerometry has been the primary tool used to estimate external load, with heart rate commonly used to quantify internal load. Supplemental to heart rate, psychophysiological and biochemical measures have also been investigated to elucidate aspects of internal load. Broadly, investigations have revealed that military training requires personnel to perform relatively large volumes of physical activity (e.g. averaging ∼15,000 steps·day−1) of typically low-moderate intensity activity (<6 MET), although considerable temporal and inter-individual variability is observed from these gross mean estimates. There are limitations associated with these measures and, at best, estimates of external and internal load can only be inferred. These limitations are particularly pertinent for military tasks such as load carriage and manual material handling, which often involve complex activities performed individually or in teams, in a range of operational environments, with multiple layers of protection, over a protracted duration. Comprehensively quantifying external and internal loads during these functional activities poses substantial practical and analytical challenges.

Variation in Evolving Optic Neuritis.

The typical natural history of optic neuritis is subjected to important exceptions. Recognition of these exceptions has led to valuable insights regarding specific etiologies of optic neuritis. Exceptions to the natural history of recovering optic neuritis are well-defined (e.g., chronic relapsing inflammatory optic neuropathy), but exceptions to the natural history of evolving optic neuritis are less so. Medical records of patients illustrating an atypical course of evolving optic neuritis were reviewed in a retrospective manner. Each patient was treated by at least one of the authors. Four patients were identified who illustrated an atypical natural history of incipient optic neuritis. Diagnoses included idiopathic optic neuritis, seropositive neuromyelitis optica spectrum disease, anti-myelin oligodendrocyte glycoprotein antibody disease, and multiple sclerosis in 1 patient each. Features of interest included an atypical temporal relationship between development of pain and onset of clinical optic neuropathy, an unusually protracted duration of pain, and an unusually long duration of worsening optic neuropathy before stabilization. This case series illustrates the substantial clinical heterogeneity which may be observed in the evolution of optic neuritis. The temporal relationship between development of pain and onset of clinical optic neuropathy, the duration of pain, and duration of worsening optic neuropathy before stabilization are all subjected to significant variability. Although most patients with optic neuritis present with painful vision loss which progresses over 1 week or less, careful attention to the exceptions described herein may facilitate earlier recognition of diagnostically challenging cases.

Racemization in cataractous lens from diabetic and aging individuals: analysis of Asp 58 residue in αA-crystallin.

Cataract is the leading cause of visual impairment globally. Racemization of lens proteins may contribute to cataract formation in aging individuals. As a special type of age-related cataract (ARC), diabetic cataract (DC) is characterized by the early onset of cortical opacification and finally developed into a mixed type of cortical and nuclear opacification. We compared racemization of Asp 58 residue, a hotspot position in αA-crystallin, from the cortex and nucleus of diabetic and age-matched senile cataractous lenses, by identifying L-Asp/L-isoAsp/D-Asp/D-isoAsp by mass spectrometry. Compared to nondiabetic cataractous lenses, DC lenses showed a significantly increased cortex/nucleus ratio of D-Asp 58, which originated primarily from an increased percentage of D-Asp 58 in the lens cortex of DC. Moreover, patients diagnosed with diabetes for over 10 years showed a lower cortex/nucleus ratio of D-isoAsp 58 in the lens compared with those who had a shorter duration of diabetes, which originated mainly from an increased percentage of D-isoAsp 58 in the lens nucleus of DC with increasing time of hyperglycemia. Further analysis confirmed decreased protein solubility in diabetic cataractous lenses. The different racemization pattern in DC may be distinguished from ARC and influence its phenotype over the protracted duration of diabetes.

High Chromosomal Stability and Immortalized Totipotency Characterize Long-Term Tissue Cultures of Chinese Ginseng (Panax Ginseng).

Chinese ginseng (Panax ginseng C. A. Meyer) is a highly cherished traditional Chinese medicine, with several confirmed medical effects and many more asserted health-boosting functions. Somatic chromosomal instability (CIN) is a hallmark of many types of human cancers and also related to other pathogenic conditions such as miscarriages and intellectual disabilities, hence, the study of this phenomenon is of wide scientific and translational medical significance. CIN also ubiquitously occurs in cultured plant cells, and is implicated as a major cause of the rapid decline/loss of totipotency with culture duration, which represents a major hindrance to the application of transgenic technologies in crop improvement. Here, we report two salient features of long-term cultured callus cells of ginseng, i.e., high chromosomal stability and virtually immortalized totipotency. Specifically, we document that our callus of ginseng, which has been subcultured for 12 consecutive years, remained highly stable at the chromosomal level and showed little decline in totipotency. We show that these remarkable features of cultured ginseng cells are likely relevant to the robust homeostasis of the transcriptional expression of specific genes (i.e., genes related to tissue totipotency and chromosomal stability) implicated in the manifestation of these two complex phenotypes. To our knowledge, these two properties of ginseng have not been observed in any animals (with respect to somatic chromosomal stability) and other plants. We posit that further exploration of the molecular mechanisms underlying these unique properties of ginseng, especially somatic chromosomal stability in protracted culture duration, may provide novel clues to the mechanistic understanding of the occurrence of CIN in human disease.

In vitro and in vivo evaluation of a lidocaine loaded polymer nanoparticle formulation co-loaded with lidocaine for local anesthetics effect

There is a crucial need for long-acting local anesthetics (LAs) that can be administered as single dose analgesics. However, owing to their low molecular mass, LAs (lidocaine, bupivacaine, procaine, ropivacaine, and benzocaine) display rapid and complete absorption. The goal of the current study (LDC@LPHNs) was to progress and assess lidocaine (LDC) hybrid lipid-polymer nanoparticles (LPHNs) in comparison to LDC-loaded PLGA NPs (LDC@NPs). The morphology, zeta potential, particle size, and drug loading abilities of the newly fabricated materials were examined. The self-assembled LDC@LPHNs combined with PLGA, DSPE-PEG2000, and lecithin were approximately 180 nm in size, were larger than LDC@LPHNs and LDC@NPs and showed a protracted in vitro drug release profile in PBS solution. Additionally, the LDC@LPHNs exhibited improved stability and less in vitro cytotoxicity. Furthermore, in vivo examination of the anesthetic properties in mice models showed that the LDC@LPHNs displayed remarkable protracted analgesic durations, which was further confirmed through histological examinations. These outcomes establish that the LDC@LPHNs could purpose as a potential framework of drug conveyance to address the disadvantages of less stability, quick release of drug, and to extend anesthetic effects with less toxicity.