A Comprehensive Phylogenomic Platform for Exploring the Angiosperm Tree of Life.

The tree of life is the fundamental biological roadmap for navigating the evolution and properties of life on Earth, and yet remains largely unknown. Even angiosperms (flowering plants) are fraught with data gaps, despite their critical role in sustaining terrestrial life. Today, high-throughput sequencing promises to significantly deepen our understanding of evolutionary relationships. Here, we describe a comprehensive phylogenomic platform for exploring the angiosperm tree of life, comprising a set of open tools and data based on the 353 nuclear genes targeted by the universal Angiosperms353 sequence capture probes. The primary goals of this article are to (i) document our methods, (ii) describe our first data release, and (iii) present a novel open data portal, the Kew Tree of Life Explorer (https://treeoflife.kew.org). We aim to generate novel target sequence capture data for all genera of flowering plants, exploiting natural history collections such as herbarium specimens, and augment it with mined public data. Our first data release, described here, is the most extensive nuclear phylogenomic data set for angiosperms to date, comprising 3099 samples validated by DNA barcode and phylogenetic tests, representing all 64 orders, 404 families (96$\%$) and 2333 genera (17$\%$). A "first pass" angiosperm tree of life was inferred from the data, which totaled 824,878 sequences, 489,086,049 base pairs, and 532,260 alignment columns, for interactive presentation in the Kew Tree of Life Explorer. This species tree was generated using methods that were rigorous, yet tractable at our scale of operation. Despite limitations pertaining to taxon and gene sampling, gene recovery, models of sequence evolution and paralogy, the tree strongly supports existing taxonomy, while challenging numerous hypothesized relationships among orders and placing many genera for the first time. The validated data set, species tree and all intermediates are openly accessible via the Kew Tree of Life Explorer and will be updated as further data become available. This major milestone toward a complete tree of life for all flowering plant species opens doors to a highly integrated future for angiosperm phylogenomics through the systematic sequencing of standardized nuclear markers. Our approach has the potential to serve as a much-needed bridge between the growing movement to sequence the genomes of all life on Earth and the vast phylogenomic potential of the world's natural history collections. [Angiosperms; Angiosperms353; genomics; herbariomics; museomics; nuclear phylogenomics; open access; target sequence capture; tree of life.].

Emerging Concepts in Vascular Dementia: A Review.

OBJECTIVE: Vascular dementia (VaD) is the second most common cause of dementia and a major health concern worldwide. A comprehensive review on VaD is warranted for better understanding and guidance for the practitioner. We provide an updated overview of the epidemiology, pathophysiological mechanisms, neuroimaging patterns as well as current diagnostic and therapeutic approaches. MATERIALS AND METHODS: A narrative review of current literature in VaD was performed based on publications from the database of PubMed, Scopus and Google Scholar up to January, 2021. RESULTS: VaD can be the result of ischemic or hemorrhagic tissue injury in a particular region of the brain which translates into clinically significant cognitive impairment. For example, a cerebral infarct in the speech area of the dominant hemisphere would translate into clinically significant impairment as would involvement of projection pathways such as the arcuate fasciculus. Specific involvement of the angular gyrus of the dominant hemisphere, with resultant Gerstman's syndrome, could have a pronounced effect on functional ability despite being termed a "minor stroke". Small vessel cerebrovascular disease can have a cumulate effect on cognitive function over time. It is unfortunately well recognized that "good" functional recovery in acute ischemic or haemorrhagic stroke, including subarachnoid haemorrhage, does not necessarily translate into good cognitive recovery. The victim may often be left unable to have gainful employment, drive a car safely or handle their affairs independently. CONCLUSIONS: This review should serve as a compendium of updated information on VaD and provide guidance in terms of newer diagnostic and potential therapeutic approaches.

Occurrence and seasonality of aflatoxin M1 in milk in two different climate zones.

BACKGROUND: Aflatoxin M1 (AFM1) is a mycotoxin found in milk as a result of the ingestion of aflatoxin B1 (AFB1) by dairy cattle. Because of its carcinogenic properties, the control of its occurrence in dairy products is of great importance. We evaluated the occurrence and seasonality of AFM1 in milk from farms with subtropical and temperate climates, where significant milk production occurs. Forty samples of raw milk were collected from bulk tansk milk during the summer (five samples from a subtropical climate and 14 from a temperate climate) and winter (six samples from a subtropical climate and 15 from a temperate climate) months of 2017 and conducted an analysis using an enzyme-linked immunosorbent assay (ELISA) (detection limit 5 ng L-1 ). Data from eight random samples were compared with respect to liquid chromatography with mass spectrometry detection and ELISA. A significant correlation was observed. RESULTS: The presence of AFM1 was detected in 87.50% (n = 35) of the samples analyzed (a mean of 16.66 ng L-1 and a median of 12.42 ng L-1 in positive samples); however, its concentration in all samples was below the maximum limit allowed by European (50 ng L-1 ) and Brazilian (500 ng L-1 ) legislations. There were no significant differences in the levels of AFM1 between the properties located in the two climate zones, in both summer and winter. The estimated daily intake of AFM1 based on the milk analyzed was 0.0107 ng kg-1 day-1 for adolescents, 0.0072 ng kg-1 day-1 for adults and 0.0098 ng kg-1 day-1 for the elderly. CONCLUSION: The present work demonstrated a low exposure to AFM1. © 2018 Society of Chemical Industry.

Synthesis and biological evaluation of potential acetylcholinesterase inhibitors based on a benzoxazine core.

With the purpose of expanding the structural variety of chemical compounds available as pharmacological tools for the treatment of Alzheimer's disease, we synthesized and evaluated a novel series of indole-benzoxazinones (Family I) and benzoxazine-arylpiperazine derivatives (Family II) for potential human acetylcholinesterase (hAChE) inhibitory properties. The most active compounds 7a and 7d demonstrated effective inhibitory profiles with Ki values of 20.3 ± 0.9 µM and 20.2 ± 0.9 µM, respectively. Kinetic inhibition assays showed non-competitive inhibition of AChE by the tested compounds. According to our docking studies, the most active compounds from both series (Families I and II) showed a binding mode similar to donepezil and interact with the same residues.

Inactivation of foodborne microorganisms using engineered water nanostructures (EWNS).

Foodborne diseases caused by the consumption of food contaminated with pathogenic microorganisms or their toxins have very serious economic and public health consequences. Here, we explored the effectiveness of a recently developed intervention method for inactivation of microorganisms on fresh produce, and food production surfaces. This method utilizes Engineered Water Nanostructures (EWNS) produced by electrospraying of water vapor. EWNS possess unique properties; they are 25 nm in diameter, remain airborne in indoor conditions for hours, contain Reactive Oxygen Species (ROS) and have very strong surface charge (on average 10 e/structure). Here, their efficacy in inactivating representative foodborne bacteria such as Escherichia coli, Salmonella enterica, and Listeria innocua, on stainless steel surfaces and on organic tomatoes, was assessed. The inactivation was facilitated using two different exposure approaches in order to optimize the delivery of EWNS to bacteria: (1) EWNS were delivered on the surfaces by diffusion and (2) a "draw through" Electrostatic Precipitator Exposure System (EPES) was developed and characterized for EWNS delivery to surfaces. Using the diffusion approach and an EWNS concentration of 24,000 #/cm3, the bacterial concentrations on the surfaces were reduced, depending on the bacterium and the surface type, by values ranging between 0.7 to 1.8 logs. Using the EPES approach and for an aerosol concentration of 50,000 #/cm3 at 90 min of exposure, results show a 1.4 log reduction for E. coli on organic tomato surfaces, as compared to the control (same conditions in regards to temperature and Relative Humidity). Furthermore, for L. innocua, the dose-response relationship was demonstrated and found to be a 0.7 and 1.2 logs removal at 12,000 and 23,000 #/cm3, respectively. The results presented here indicate that this novel, chemical-free, and environmentally friendly intervention method holds potential for development and application in the food industry, as a "green" alternative to existing disinfection methods.

Hounsfield unit changes over time in contusions of the brain.

In the United States, traumatic brain injuries are an important cause of death and disability, often with significant financial and legal consequences. Although it is generally accepted by neuroradiologists that the density of cerebral contusions decreases over time, previous research has not addressed this phenomenon directly. In the current study, we reviewed charts of patients who had suffered cerebral contusions and had at least two subsequent computed tomography scans in order to determine whether Hounsfield Units, a measure of density, decreased over time. We found that 100% of contusions decreased in Hounsfield Units over time. In addition, we found that the rate of decrease in density appears to be higher in the first 100 days after the injury. These findings are especially applicable in the area of forensics. For example, they could be used to determine the relative age of two separate brain contusions in the same patient.

Radiological evolution of relapsing polychondritis.

Relapsing Polychondritis (RP) is a systemic condition characterized by chronic, episodic inflammation, especially of cartilaginous and proteoglycan-rich structures. The etiology of this rare autoimmune disease is unknown, and so far, there is very little data available for non-Caucasians. RP presents with a constellation of non-specific inflammation, which sometimes appear in characteristic locations. Radiology is important in supporting the diagnosis, and this paper presents a case of a non-Caucasian patient monitored radiologically from early onset to the terminal stages.

Ronapreve (REGN-CoV; casirivimab and imdevimab) reduces the viral burden and alters the pulmonary response to the SARS-CoV-2 Delta variant (B.1.617.2) in K18-hACE2 mice using an experimental design reflective of a treatment use case.

With some exceptions, global policymakers have recommended against the use of existing monoclonal antibodies in COVID-19 due to loss of neutralization of newer variants. The purpose of this study was to investigate the impact of Ronapreve on compartmental viral replication using paradigms for susceptible and insusceptible variants. Virological efficacy and impact on pathogenicity was assessed in K18-hACE2 mice inoculated with either the Delta or BA.1 Omicron variants. Ronapreve reduced sub-genomic viral RNA levels in lung and nasal turbinate, 4 and 6 days post-infection, for the Delta variant but not the Omicron variant. It also blocked brain infection, which is seen with high frequency in K18-hACE2 mice after Delta variant infection. At day 6, the inflammatory response to lung infection with the Delta variant was altered to a multifocal granulomatous inflammation in which the virus appeared to be confined. The current study provides evidence of an altered tissue response to SARS-CoV-2 after treatment with a monoclonal antibody combination that retains neutralization activity. These data demonstrate that experimental designs that reflect treatment use cases are achievable in animal models for monoclonal antibodies. Extreme caution should be taken when interpreting prophylactic experimental designs that may not be representative of treatment.IMPORTANCEFollowing the emergence of the SARS-CoV-2 Omicron variant, the WHO recommended against the use of Ronapreve in its COVID-19 treatment guidelines due to a lack of efficacy based on current pharmacokinetic-pharmacodynamic understanding. However, the continued use of Ronapreve, specifically in vulnerable patients, was advocated by some based on in vitro neutralization data. Here, the virological efficacy of Ronapreve was demonstrated in both the lung and brain compartments using Delta as a paradigm for a susceptible variant. Conversely, a lack of virological efficacy was demonstrated for the Omicron variant. Comparable concentrations of both monoclonal antibodies were observed in the plasma of Delta- and Omicron-infected mice. This study made use of a reliable murine model for SARS-CoV-2 infection, an experimental design reflective of treatment, and demonstrated the utility of this approach when assessing the effectiveness of monoclonal antibodies.

Neurosarcoidosis: clinical features, diagnosis, and management.

Sarcoidosis is a multisystemic granulomatous disease, which uncommonly affects nervous system. However, when present, it may affect both central and peripheral nervous systems and potentially mimics other chronic diseases of the nervous system. Pathogenesis of neurosarcoidosis remains largely unknown, and its diagnosis and management pose serious challenges to clinicians. Early diagnosis and aggressive treatment of neurosarcoidosis are necessary to produce satisfactory clinical outcomes. This review discusses clinical manifestations, current diagnostic studies, and currently available modalities for management of neurosarcoidosis.

Occurrence of extensive spherical amyloid deposits in a prolactin-secreting pituitary macroadenoma: a radiologic-pathologic correlation.

Pituitary adenomas are the most common tumors of the sellar region, but the occurrence of spherical amyloid deposits in a pituitary adenoma is rare. We describe the clinical features, radiologic characteristics, and pathologic findings of 45-year-old man who presented with galactorrhea, hypogonadism, and hyperprolactinemia who had a pituitary adenoma with extensive spherical amyloid deposits. Approximately 30 cases have been reported, almost exclusively in patients with prolactinomas. Treatment with dopaminergic agonists will result in the expected reduction in prolactin levels; however, in most cases, macroadenomas with spherical amyloid deposits fail to decrease in size. The source of the amyloid deposits in prolactinomas is not clearly defined but may be due to abnormal processing of prolactin or its prohormone. These adenomas with spherical amyloid have a characteristic appearance on magnetic resonance imaging with low or heterogeneous intensity on T1 and low intensity on T2-weighted images. Following infusion of gadolinium, there is enhancement of the periphery but not most of the tumor mass. These magnetic resonance imaging characteristics are different than those of typical pituitary adenomas. These differences should alert clinicians to the possibility of extensive spherical amyloid deposits in a prolactin-secreting pituitary adenoma, which may have important clinical implications. In this report, we correlate the radiologic finds with the pathology and compared them with other sellar and parasellar lesions.

A case of glioblastoma in infarcted brain.

Patients with occult cancer of systemic or intracranial origin may clinically present with stroke as an initial manifestation due to tumor-associated hemorrhage and/or infarction. Such cases are usually clearly temporally related. We present a case with separate instances of hemorrhagic infarction and subsequent glioblastoma that were temporally separated by several years. This case may be an illustration of recent findings in mechanisms of brain repair and tumor biology.

Understanding the Degradation of Core-Shell Nanogels Using Asymmetrical Flow Field Flow Fractionation.

Nanogels are candidates for biomedical applications, and core-shell nanogels offer the potential to tune thermoresponsive behaviour with the capacity for extensive degradation. These properties were achieved by the combination of a core of poly(N-isopropylmethacrylamide) and a shell of poly(N-isopropylacrylamide), both crosslinked with the degradable crosslinker N,N'-bis(acryloyl)cystamine. In this work, the degradation behaviour of these nanogels was characterised using asymmetric flow field flow fractionation coupled with multi-angle and dynamic light scattering. By monitoring the degradation products of the nanogels in real-time, it was possible to identify three distinct stages of degradation: nanogel swelling, nanogel fragmentation, and nanogel fragment degradation. The results indicate that the core-shell nanogels degrade slower than their non-core-shell counterparts, possibly due to a higher degree of self-crosslinking reactions occurring in the shell. The majority of the degradation products had molecule weights below 10 kDa, which suggests that they may be cleared through the kidneys. This study provides important insights into the design and characterisation of degradable nanogels for biomedical applications, highlighting the need for accurate characterisation techniques to measure the potential biological impact of nanogel degradation products.

Ronapreve (REGN-CoV; casirivimab and imdevimab) reduces the viral burden and alters the pulmonary response to the SARS-CoV-2 Delta variant (B.1.617.2) in K18-hACE2 mice using an experimental design reflective of a treatment use case.

Background: Ronapreve demonstrated clinical application in post-exposure prophylaxis, mild/moderate disease and in the treatment of seronegative patients with severe COVID19 prior to the emergence of the Omicron variant in late 2021. Numerous reports have described loss of in vitro neutralisation activity of Ronapreve and other monoclonal antibodies for BA.1 Omicron and subsequent sub-lineages of the Omicron variant. With some exceptions, global policy makers have recommended against the use of existing monoclonal antibodies in COVID19. Gaps in knowledge regarding the mechanism of action of monoclonal antibodies are noted, and further preclinical study will help understand positioning of new monoclonal antibodies under development. Objectives: The purpose of this study was to investigate the impact of Ronapreve on compartmental viral replication as a paradigm for a monoclonal antibody combination. The study also sought to confirm absence of in vivo activity against BA.1 Omicron (B.1.1.529) relative to the Delta (B.1.617.2) variant. Methods: Virological efficacy of Ronapreve was assessed in K18-hACE2 mice inoculated with either the SARS-CoV-2 Delta or Omicron variants. Viral replication in tissues was quantified using qRT-PCR to measure sub-genomic viral RNA to the E gene (sgE) as a proxy. A histological examination in combination with staining for viral antigen served to determine viral spread and associated damage. Results: Ronapreve reduced sub-genomic viral RNA levels in lung and nasal turbinate, 4 and 6 days post infection, for the Delta variant but not the Omicron variant of SARS-CoV-2 at doses 2-fold higher than those shown to be active against previous variants of the virus. It also appeared to block brain infection which is seen with high frequency in K18-hACE2 mice after Delta variant infection. At day 6, the inflammatory response to lung infection with the Delta variant was altered to a mild multifocal granulomatous inflammation in which the virus appeared to be confined. A similar tendency was also observed in Omicron infected, Ronapreve-treated animals. Conclusions: The current study provides evidence of an altered tissue response to the SARS-CoV-2 after treatment with a monoclonal antibody combination that retains neutralization activity. These data also demonstrate that experimental designs that reflect the treatment use case are achievable in animal models for monoclonal antibodies deployed against susceptible variants. Extreme caution should be taken when interpreting prophylactic experimental designs when assessing plausibility of monoclonal antibodies for treatment use cases.

Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters.

Pibrentasvir (PIB) has been demonstrated to block exonuclease activity of the SARS-CoV-2 polymerase, protecting favipiravir (FVP) and remdesivir (RDV) from post-incorporation excision and eliciting antiviral synergy in vitro. The present study investigated the chemoprophylactic efficacy of PIB, FVP, RDV, FVP with PIB, or RDV with PIB dosed intranasally twice a day, using a Syrian golden hamster contact transmission model. Compared to the saline control, viral RNA levels were significantly lower in throat swabs in FVP (day 7), RDV (day 3, 5, 7), and RDV+PIB (day 3, 5) treatment groups. Similarly, findings were evident for nasal turbinate after PIB and RDV treatment, and lungs after PIB, FVP, and FVP+PIB treatment at day 7. Lung viral RNA levels after RDV and RDV+PIB treatment were only detectable in two animals per group, but the overall difference was not statistically significant. In situ examination of the lungs confirmed SARS-CoV-2 infection in all animals, except for one in each of the RDV and RDV+PIB treatment groups, which tested negative in all virus detection approaches. Overall, prevention of transmission was observed in most animals treated with RDV, while other agents reduced the viral load following contact transmission. No benefit of combining FVP or RDV with PIB was observed.

Evaluation of Nafamostat as Chemoprophylaxis for SARS-CoV-2 Infection in Hamsters.

The successful development of a chemoprophylaxis against SARS-CoV-2 could provide a tool for infection prevention that is implementable alongside vaccination programmes. Nafamostat is a serine protease inhibitor that inhibits SARS-CoV-2 entry in vitro, but it has not been characterised for chemoprophylaxis in animal models. Clinically, nafamostat is limited to intravenous delivery and has an extremely short plasma half-life. This study sought to determine whether intranasal dosing of nafamostat at 5 mg/kg twice daily was able to prevent the airborne transmission of SARS-CoV-2 from infected to uninfected Syrian Golden hamsters. SARS-CoV-2 RNA was detectable in the throat swabs of the water-treated control group 4 days after cohabitation with a SARS-CoV-2 inoculated hamster. However, throat swabs from the intranasal nafamostat-treated hamsters remained SARS-CoV-2 RNA negative for the full 4 days of cohabitation. Significantly lower SARS-CoV-2 RNA concentrations were seen in the nasal turbinates of the nafamostat-treated group compared to the control (p = 0.001). A plaque assay quantified a significantly lower concentration of infectious SARS-CoV-2 in the lungs of the nafamostat-treated group compared to the control (p = 0.035). When taken collectively with the pathological changes observed in the lungs and nasal mucosa, these data are strongly supportive of the utility of intranasally delivered nafamostat for the prevention of SARS-CoV-2 infection.

ß-Cyclodextrin-Based Nanosponges Inclusion Compounds Associated with Gold Nanorods for Potential NIR-II Drug Delivery.

This article describes the synthesis and characterization of two nanocarriers consisting of ß-cyclodextrin-based nanosponges (NSs) inclusion compounds (ICs) and gold nanorods (AuNRs) for potential near-infrared II (NIR-II) drug-delivery systems. These nanosystems sought to improve the stability of two drugs, namely melphalan (MPH) and curcumin (CUR), and to trigger their photothermal release after a laser irradiation stimulus (1064 nm). The inclusion of MPH and CUR inside each NS was confirmed by field emission scanning electron microscopy (FE-SEM), Raman spectroscopy, Fourier transform infrared spectroscopy, (FT-IR) differential scanning calorimetry (DSC), transmission electron microscopy (TEM), and proton nuclear magnetic resonance (1H-NMR). Furthermore, the association of AuNRs with both ICs was confirmed by FE-SEM, energy-dispersive spectroscopy (EDS), TEM, dynamic light scattering (DLS), ζ-potential, and UV-Vis. Moreover, the irradiation assays demonstrated the feasibility of the controlled-photothermal drug release of both MPH and CUR in the second biological window (1000-1300 nm). Finally, MTS assays depicted that the inclusion of MPH and CUR inside the cavities of NSs reduces the effects on mitochondrial activity, as compared to that observed in the free drugs. Overall, these results suggest the use of NSs associated with AuNRs as a potential technology of controlled drug delivery in tumor therapy, since they are efficient and non-toxic materials.

The Spectrum of Acute Cerebrovascular Disease in Patients with COVID-19.

(1) Background: COVID-19 infection is responsible for the ongoing pandemic and acute cerebrovascular disease (CVD) has been observed in COVID-19 patients. (2) Methods: We conducted a retrospective, observational study of hospitalized adult patients admitted to our hospital with SARS-CoV-2 and acute cerebrovascular disease. All clinical data were reviewed including epidemiology, clinical features, laboratory data, neuroradiological findings, hospital management and course from 32 patients hospitalized for COVID-19 management with acute cerebrovascular disease. (3) Results: Acute CVD with COVID-19 was associated with higher NIH stroke scale on discharge compared to non-COVID-19 CVDs. Seizures complicated the hospital course in 16% of COVID-19 patients with CVD. The majority of the acute CVDs were ischemic (81%) in nature followed by hemorrhagic (22%). Acute CVD with COVID-19 resulted in average hospital stays greater than twice that of the control group (13 days in COVID-19, 5 days in control). Acute CVD with COVID-19 patients had worse clinical outcomes with 31% patient deaths and 6% discharged to hospice. In the control group, 6% of patients died. (4) Conclusions: Acute CVD associated with COVID-19 tends to be more complicated with unique and adverse clinical phenotype, longer hospital admissions, and worse clinical outcomes.

The effects of high dose interferon-ß1a on plasma microparticles: correlation with MRI parameters.

OBJECTIVES: We previously reported a correlation between levels of micro particles carrying CD31 (PMP(CD31+)) and disease activity in MS. However, the effects of long term (12 month) treatment with high dose, high frequency interferon-ß1a (Rebif™) on plasma levels of PMP(CD31+), PMP(CD146+), and PMP(CD54+) and MRI measures of disease activity have not yet been assessed. METHODS: During this prospective 1-year study, we used flow cytometry to measure changes in plasma micro particles (PMP) bearing CD31 (PMP(CD31+)), CD146 (PMP(CD146+)), and CD54/ICAM-1 (PMP(CD54+)) in 16 consecutive patients with relapsing-remitting MS (RRMS) before and after 3, 6, and 12 months of subcutaneous therapy with interferon-beta1a (44 micrograms, 3X weekly). At each visit, clinical exams and expanded disability status scale (EDSS) scores were recorded. RESULTS: Plasma levels of PMP(CD31+), and PMP(CD54+) were significantly reduced by treatment with IFN-ß1a. PMP(CD146+) appeared to decrease only at 3 months and did not persist at 6 and 12 months (p = 0.0511). In addition, the decrease in plasma levels of PMP(CD31+) and PMP(CD54+) levels at 12 months were associated with a significant decrease in the number and volume of contrast enhancing T1-weigthed lesions. CONCLUSION: Our data suggest that serial measurement of plasma micro particles (PMP), particularly in the initial stages of MS (when neuro-inflammatory cascades are more intense), may serve as reliable and reproducible surrogate markers of response to IFN-ß1a therapy for MS. In addition, the progressive decline in plasma levels of PMP(CD31+) and PMP(CD54+) further supports the concept that IFN-ß1a exerts stabilizing effect on the cerebral endothelial cells during pathogenesis of MS.

Electromagnetic hypersensitivity: evidence for a novel neurological syndrome.

OBJECTIVE: We sought direct evidence that acute exposure to environmental-strength electromagnetic fields (EMFs) could induce somatic reactions (EMF hypersensitivity). METHODS: The subject, a female physician self-diagnosed with EMF hypersensitivity, was exposed to an average (over the head) 60-Hz electric field of 300 V/m (comparable with typical environmental-strength EMFs) during controlled provocation and behavioral studies. RESULTS: In a double-blinded EMF provocation procedure specifically designed to minimize unintentional sensory cues, the subject developed temporal pain, headache, muscle twitching, and skipped heartbeats within 100 s after initiation of EMF exposure (p < .05). The symptoms were caused primarily by field transitions (off-on, on-off) rather than the presence of the field, as assessed by comparing the frequency and severity of the effects of pulsed and continuous fields in relation to sham exposure. The subject had no conscious perception of the field as judged by her inability to report its presence more often than in the sham control. DISCUSSION: The subject demonstrated statistically reliable somatic reactions in response to exposure to subliminal EMFs under conditions that reasonably excluded a causative role for psychological processes. CONCLUSION: EMF hypersensitivity can occur as a bona fide environmentally inducible neurological syndrome.

Transfersomes as alternative topical nanodosage forms for the treatment of skin disorders.

Topical drug delivery is a promising approach to treat different skin disorders. However, it remains a challenge mainly due to the nature and rigidity of the nanosystems, which limit deep skin penetration, and the unsuccessful demonstration of clinical benefits; greater penetration by itself, does not ensure pharmacological success. In this context, transfersomes have appeared as promising nanosystems; deformability, their unique characteristic, allows them to pass through the epidermal microenvironment, improving the skin drug delivery. This review focuses on the comparison of transfersomes with other nanosystems (e.g., liposomes), discusses recent therapeutic applications for the topical treatment of different skin disorders and highlights the need for further studies to demonstrate significant clinical benefits of transfersomes compared with conventional therapies.