Multiple Dermatomyofibromas in a Patient with Ehlers-Danlos Syndrome.

Dermatomyofibromas are a rare, benign, acquired neoplasm with less than 150 reported cases worldwide. The etiologic factors that contribute to the development of these lesions are currently unknown. To our knowledge, there have been only six previously reported cases of patients presenting with multiple dermatomyofibromas, and in each of these cases, there were less than ten lesions present. Herein, we describe a patient who developed more than 100 dermatomyofibromas over a period of years, and we argue that the patient's concurrent Ehlers-Danlos syndrome could have contributed to this unique presentation by inducing an increased fibroblast-to-myofibroblast transition.

An intranasally administrated SARS-CoV-2 beta variant subunit booster vaccine prevents beta variant viral replication in rhesus macaques

Emerging of SARS-CoV-2 variants and waning of vaccine/infection-induced immunity poses threats to curbing the COVID-19 pandemic. An effective, safe, and convenient booster vaccine will be needed. We hypothesized that a variant-modified mucosal booster vaccine might induce local immunity to prevent SARS-CoV-2 infection at the port of entry. The beta-variant is hardest to cross-neutralize. Herein we assessed the protective efficacy of an intranasal booster composed of beta variant-spike protein S1 with IL-15 and TLR agonists in previously immunized macaques. The macaques were first vaccinated with Wuhan strain S1 with the same adjuvant. One year later, negligibly detectable SARS-CoV-2-specific antibody remained. Nevertheless, the booster induced vigorous humoral immunity including serum- and bronchoalveolar lavage (BAL)-IgG, secretory nasal- and BAL-IgA, and neutralizing antibody against the original strain and/or beta variant. Beta-variant S1-specifc CD4+ and CD8+ T cell responses were also elicited in PBMC and BAL. Following SARS-CoV-2 beta variant challenge, the vaccinated group demonstrated significant protection against viral replication in the upper and lower respiratory tracts, with almost full protection in the nasal cavity. The fact that one intranasal beta-variant booster administrated one year after the first vaccination provoked protective immunity against beta variant infections may inform future SARS-CoV-2 booster design and administration timing.

Protective Efficacy of Gastrointestinal SARS-CoV-2 Delivery Against Intranasal and Intratracheal SARS-CoV-2 Challenge in Rhesus Macaques

Live oral vaccines have been explored for their protective efficacy against respiratory viruses, particularly for adenovirus serotypes 4 and 7. The potential of a live oral vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however, remains unclear. In this study, we assessed the immunogenicity of live SARS-CoV-2 delivered to the gastrointestinal tract in rhesus macaques and its protective efficacy against intranasal and intratracheal SARS-CoV-2 challenge. Post-pyloric administration of SARS-CoV-2 by esophagogastroduodenoscopy resulted in limited virus replication in the gastrointestinal tract and minimal to no induction of mucosal antibody titers in rectal swabs, nasal swabs, and bronchoalveolar lavage. Low levels of serum neutralizing antibodies were induced and correlated with modestly diminished viral loads in nasal swabs and bronchoalveolar lavage following intranasal and intratracheal SARS-CoV-2 challenge. Overall, our data show that post-pyloric inoculation of live SARS-CoV-2 is weakly immunogenic and confers partial protection against respiratory SARS-CoV-2 challenge in rhesus macaques. ImportanceSARS-CoV-2 remains a global threat, despite the rapid deployment but limited coverage of multiple vaccines. Alternative vaccine strategies that have favorable manufacturing timelines, greater ease of distribution and improved coverage may offer significant public health benefits, especially in resource-limited settings. Live oral vaccines have the potential to address some of these limitations; however no studies have yet been conducted to assess the immunogenicity and protective efficacy of a live oral vaccine against SARS-CoV-2. Here we report that oral administration of live SARS-CoV-2 in non-human primates may offer prophylactic benefits, but that formulation and route of administration will require further optimization.

Dataset of COVID-19 outbreak and potential predictive features in the USA

This dataset provides information related to the outbreak of COVID-19 disease in the United States, including data from each of 3142 US counties from the beginning of the outbreak (January 2020) until September 2020. This data is collected from many public online databases and includes the daily number of COVID-19 confirmed cases and deaths, as well as 33 features that may be relevant to the pandemic dynamics: demographic, geographic, climatic, traffic, public-health, social-distancing-policy adherence, and political characteristics of each county. We anticipate many researchers will use this dataset to train models that can predict the spread of COVID-19 and to identify the key driving factors.

Two examples of 'cuboid syndrome' with active bone pathology: why did manual therapy help?

Cuboid syndrome describes lateral midfoot pain localised to the cuboid bone. Previously reported case studies promoted joint mobilisation or manipulation interventions. The assumed mechanism was correction of a subtle disruption to the calcaneocuboid joint position. There is an absence of evidence for correction of joint position, but there is evidence of neurophysiological mechanisms for pain modulation. This case study reports on a patient who suffered two occurrences of cuboid syndrome on opposite feet, three years apart. With both occurrences, joint mobilisation achieved rapid and lasting resolution of severe pain and functional limitations. This occurred despite the presence of an active bone pathology at the symptomatic cuboid (demonstrated with nuclear imaging), which could represent a stress reaction, transient osteoporosis, ischaemic necrosis, infection or neoplasm. This case contributes three considerations for clinical reasoning and manual therapy research. 1. Active local bone pathology could exist in other patients with pain at the cuboid, and other conditions where symptoms resolve with joint mobilisation. 2. Rapid and lasting symptom resolution fits with a hypothesis that joint mobilisation acted to reverse neurological sensitisation. 3. Lasting symptom resolution may be clinically associated with manual therapy, but mechanisms extending beyond temporary analgesia are yet to be identified.

Dual nano-electrospray for probing solution interactions and fast reactions of complex biomolecules.

A novel nano-electrospray emitter has been developed containing two separated channels running throughout the length of the emitter. The emitters have been fabricated from "theta-shaped" borosilicate capillaries. Loading of different solutions into the two different channels opens up the possibility to study short timescale interactions within a Taylor cone common to both channels. The common Taylor cone constitutes an extremely small "mixing volume" of the order of femtolitres. The products of electrospray from the dual-channel emitters have been analysed by Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry. Results are presented for interactions of vancomycin with diacetyl-L-lysyl-D-alanyl- D-alanine and interactions of vancomycin with deuterated vancomycin. On the basis of these results, it is concluded that, during electrospray, specific non-covalent adducts have been formed and that there have been exchange reactions involving making and breaking of covalent bonds.

Diabetes: glycaemic control in type 1.

INTRODUCTION: Type 1 diabetes occurs when destruction of the pancreatic islet beta cells, usually attributable to an autoimmune process, causes the pancreas to produce too little insulin or none at all. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of intensive treatment programmes, psychological interventions, and educational interventions in adults and adolescents with type 1 diabetes? What are the effects of different insulin regimens or frequency of blood glucose monitoring in adults and adolescents with type 1 diabetes? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 42 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review, we present information relating to the effectiveness and safety of the following interventions: different frequencies of insulin administration (continuous subcutaneous insulin infusion compared with multiple daily subcutaneous insulin injections), different frequencies of blood glucose self-monitoring (including continuous blood glucose monitoring compared with intermittent/conventional monitoring), educational interventions, intensive treatment programmes, and psychological interventions.

Gastric volvulus in infants and children.

INTRODUCTION: Gastric volvulus is an important cause of nonbilious emesis that must be recognized early to ensure a good outcome. We reviewed 7 cases from our institution, Children's Healthcare of Atlanta (Egleston campus). In addition, we reviewed all gastric volvulus cases in children published to date in the English literature to draw general conclusions about the presentation and treatment of this unusual disease. METHODS: An electronic literature search was performed to find all published cases of pediatric gastric volvulus. The care of all children from January 2002 to December 2007 who were treated for gastric volvulus was also reviewed. RESULTS: There have been 581 cases of gastric volvulus in children published in English between 1929 and 2007. Of these, 252 were acute and 329 were chronic cases. The most common presentation of acute gastric volvulus is in a child <5 years old with nonbilious emesis, epigastric distention, and abdominal pain. Acute gastric volvulus is often associated with deformities of adjacent organs. Definitive diagnosis is made with upper gastrointestinal studies, and definitive therapy requires repair of associated defects and anterior fixation of the stomach to the abdominal wall. The most common presentation of chronic volvulus is in an infant <1 year old with emesis, epigastric distention, feeding difficulties, and growth failure. Treatment may be medical or surgical depending on the underlying etiology of the volvulus. CONCLUSIONS: Acute gastric volvulus is a potentially life-threatening occurrence with a good outcome when treated in a timely fashion. Chronic volvulus may be more difficult to recognize. The common features of acute and chronic gastric volvulus described in this review should assist pediatric health care providers in promptly diagnosing and treating this disease.

The use of acupuncture in dentistry.

UNLABELLED: Acupuncture is an ancient technique that has regained popularity in the UK over the last 20 years or so. This paper gives an overview in the concepts of acupuncture, both traditional and western, and indicates some of the appropriate uses for the technique in dental practice. CLINICAL RELEVANCE: Acupuncture has an important role to play in improving the quality of care that can be delivered for dental patients, particularly around the management of the gag reflex, and treatment of temporomandibular disorders (TMD).

Highly selective 5-substitution of 3-methylthiophene via directed lithiation.

Lithiation of 3-methylthiophene with lithium 2,2,6,6-tetra-methylpiperidide (LiTMP) is highly selective at the 5-position, and reaction with a range of electrophiles gives high yields of the corresponding 2,4-disubstituted thiophenes, even when unhindered electrophiles are used.

Application and evaluation of solvent-free matrix-assisted laser desorption/ionization mass spectrometry for the analysis of derivatized fullerenes.

A variety of derivatized fullerenes have been studied by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. Of particular emphasis has been the evaluation of a recently introduced solvent-free sample/target preparation method. Solvent-free MALDI is particularly valuable in overcoming adverse solvent-related effects, such as insolubility and/or degradation of the sample. The method was applied to fullerene derivatives susceptible to decomposition under insufficiently "soft" MALDI conditions. Analytes included the hydrofullerene: C(60)H(36), fluorofullerenes: C(60)F(x) where x = 18, 36, 46, 48 and C(70)F(x) where x = 54, 56, methano-bridged amphiphilic ligand adducts to C(60) and the [4 + 2] cycloadduct of tetracene to C(60). The new solvent-free sample preparation is established as an exceedingly valuable addition to the repertoire of preparation protocols within MALDI. The MALDI mass spectra were of very high quality throughout, providing a testimony that "soft" MALDI conditions could be achieved. Using the [4 + 2] cycloadduct of tetracene to C(60) as the model analyte for direct comparison with solvent-based MALDI, the solvent-free approach led to less fragmentation and more abundant analyte ions. Applying solvent-free sample preparation, different matrix compounds have been examined for use in the MALDI of derivatized fullerenes, including sulfur, tetracyanoquinodimethane (TCNQ), 9-nitroanthracene (9-NA) and trans-2-[3-(4-tert-butylphenyl)-2-methyl-2- propenylidene]malononitrile (DCTB). DCTB was confirmed as the best performing matrix, reducing unwanted decomposition and suppression effects.