Safety and Immunogenicity of Radiation-Attenuated PfSPZ Vaccine in Equatoguinean Infants, Children, and Adults.

The radiation-attenuated Plasmodium falciparum sporozoites (PfSPZ) Vaccine has demonstrated safety and immunogenicity in 5-month-old to 50-year-old Africans in multiple trials. Except for one, each trial has restricted enrollment to either infants and children or adults < 50 years old. This trial was conducted in Equatorial Guinea and assessed the safety, tolerability, and immunogenicity of three direct venous inoculations of 1.8 × 106 or 2.7 × 106 PfSPZ, of PfSPZ Vaccine, or normal saline administered at 8-week intervals in a randomized, double-blind, placebo-controlled trial stratified by age (6-11 months and 1-5, 6-10, 11-17, 18-35, and 36-61 years). All doses were successfully administered. In all, 192/207 injections (93%) in those aged 6-61 years were rated as causing no or mild pain. There were no significant differences in solicited adverse events (AEs) between vaccinees and controls in any age group (P ≥ 0.17). There were no significant differences between vaccinees and controls with respect to the rates or severity of unsolicited AEs or laboratory abnormalities. Development of antibodies to P. falciparum circumsporozoite protein occurred in 67/69 vaccinees (97%) and 0/15 controls. Median antibody levels were highest in infants and 1-5-year-olds and declined progressively with age. Antibody responses in children were greater than in adults protected against controlled human malaria infection. Robust immunogenicity, combined with a benign AE profile, indicates children are an ideal target for immunization with PfSPZ Vaccine.

Effects of in-the-bag dry-ageing on meat quality, palatability and volatile compounds of low-value beef cuts.

This study evaluated the effects of in-the-bag dry-ageing (BDA) (21 and 42 d) on meat quality, palatability, and volatile compounds of clod heart, brisket, and flat iron cuts from steers. In all cuts, BDA increased moisture losses (P < 0.05), but this did not reduce the juiciness of 21 d BDA versus wet-aged (WA) steaks. In clod heart, BDA increased overall tenderness at 21 d compared to 21 d WA (P < 0.01). Regardless of ageing period, BDA of clod heart increased beef flavour and salty taste and decreased sour-dairy and stale/cardboard flavours and concentrations of volatile compounds derived from lipid oxidation compared to WA (P < 0.05). In brisket, BDA increased salty taste and fatty aroma and reduced bloody/serumy flavour, whereas decreased beef and buttery flavours and intensified some unpleasant aromas/flavours (P < 0.05) for both ageing periods. The BDA of flat iron increased several undesirable aromas/flavours and decreased sweet taste and beef and buttery flavours (P < 0.05), regardless of ageing period. Overall, BDA for 42 d decreased meat quality and palatability and increased concentrations of volatile compounds from lipid oxidation, especially in flat iron cuts. Value could be recovered by customizing BDA periods by cut.

The role of multiparametric magnetic resonance in active surveillance of a low-risk prostate cancer cohort from clinical practice.

INTRODUCTION: Active surveillance (AS) is considered a suitable management practice for those patients with low-risk prostate cancer (PCa). At present, however, the role of multiparametric magnetic resonance imaging (mpMRI) in AS protocols has not yet been clearly established. OUTCOMES: To determine the role of mpMRI and its ability to detect significant prostate cancer (SigPCa) in PCa patients enrolled in AS protocols. MATERIALS AND METHODS: There were 229 patients enrolled in an AS protocol between 2011 and 2020 at Reina Sofía University Hospital. MRI interpretation was based on PIRADS v.1 or v.2/2.1 classification. Demographics, clinical, and analytical data were collected and analyzed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for mpMRI in different scenarios. We defined SigPCa and reclassification/progression as a Gleason score (GS) ≥ 3 + 4, a clinical stage ≥T2b, or an increase in PCa volume. Kaplan-Meier and log-rank tests were used to estimate progression-free survival time. RESULTS: Median age was 69.02 (±7.73) at diagnosis, with a 0.15 (±0.08) PSA density (PSAD). Eighty-six patients were reclassified after confirmatory biopsy, with a suspicious mpMRI an indication for a clear reclassification and risk-predictor factor in disease progression (p < 0.05). During follow-up, 46 patients were changed from AS to active treatment mainly due to disease progression. Ninety patients underwent ≥2mpMRI during follow-up, with a median follow-up of 29 (15-49) months. Thirty-four patients had a baseline suspicious mpMRI (at diagnostic or confirmatory biopsy): 14 patients with a PIRADS 3 and 20 patients with ≥PIRADS 4. From 14 patients with a PIRADS 3 baseline mpMRI, 29% progressed radiologically, with a 50% progression rate versus 10% (1/10 patients) for those with similar or decreased mpMRI risk. Of the 56 patients with a non-suspicious baseline mpMRI (PIRADS < 2), 14 patients (25%) had an increased degree of radiological suspicion, with a detection rate of SigPCa of 29%. The mpMRI NPV during follow-up was 0.91. CONCLUSION: A suspicious mpMRI increases the reclassification and disease progression risk during follow-up and plays an important role in monitoring biopsies. In addition, a high NPV at mpMRI follow-up can help to decrease the need to monitor biopsies during AS.

[Atypical growth of an intracranial lipoma]. / Crecimiento atípico en un lipoma intracraneal.

TITLE: Crecimiento atípico en un lipoma intracraneal.

[2022 Practice guidelines for the management of arterial hypertension of the Spanish Society of Hypertension]. / Guía práctica sobre el diagnóstico y tratamiento de la hipertensión arterial en España, 2022. Sociedad Española de Hipertensión - Liga Española para la Lucha contra la Hipertensión Arterial (SEH-LELHA).

Hypertension is the most important risk factor for global disease burden. Detection and management of hypertension are considered as key issues for individual and public health, as adequate control of blood pressure levels markedly reduces morbidity and mortality associated with hypertension. Aims of these practice guidelines for the management of arterial hypertension of the Spanish Society of Hypertension include offering simplified schemes for diagnosis and treatment for daily practice, and strategies for public health promotion. The Spanish Society of Hypertension assumes the 2018 European guidelines for management of arterial hypertension developed by the European Society of Cardiology and the European Society of Hypertension, although relevant aspects of the 2017 American College of Cardiology/American Heart Association guidelines and the 2020 International Society of Hypertension guidelines are also commented. Hypertension is defined as a persistent elevation in office systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mmHg, and assessment of out-of-office blood pressure and global cardiovascular risk are considered of key importance for evaluation and management of hypertensive patients. The target for treated blood pressure should be < 130/80 for most patients. The treatment of hypertension involves lifestyle interventions and drug therapy. Most people with hypertension need more than one antihypertensive drug for adequate control, so initial therapy with two drugs, and single pill combinations are recommended for a wide majority of hypertensive patients.

BIPSPI+: Mining Type-Specific Datasets of Protein Complexes to Improve Protein Binding Site Prediction.

Computational approaches for predicting protein-protein interfaces are extremely useful for understanding and modelling the quaternary structure of protein assemblies. In particular, partner-specific binding site prediction methods allow delineating the specific residues that compose the interface of protein complexes. In recent years, new machine learning and other algorithmic approaches have been proposed to solve this problem. However, little effort has been made in finding better training datasets to improve the performance of these methods. With the aim of vindicating the importance of the training set compilation procedure, in this work we present BIPSPI+, a new version of our original server trained on carefully curated datasets that outperforms our original predictor. We show how prediction performance can be improved by selecting specific datasets that better describe particular types of protein interactions and interfaces (e.g. homo/hetero). In addition, our upgraded web server offers a new set of functionalities such as the sequence-structure prediction mode, hetero- or homo-complex specialization and the guided docking tool that allows to compute 3D quaternary structure poses using the predicted interfaces. BIPSPI+ is freely available at https://bipspi.cnb.csic.es.

Effect of in-the-bag dry-ageing on meat palatability and volatile compounds of cull cows and youthful steers.

This study evaluated the effects of in-the-bag dry-ageing on eating quality and volatile compounds of longissimus lumborum from cows and steers. Compared to wet-ageing, in-the-bag dry-ageing increased purge loss (P < 0.0001), cooking time (P < 0.0001), salty taste (P < 0.05) and sour-dairy flavour (P < 0.01), whereas decreased cooking loss (P < 0.0001), amount of perceptible connective tissue (P < 0.05) and livery flavour (P < 0.05) in both cow and steer meat. This dry-ageing technology also increased juiciness (P < 0.01) and brown-roasted aroma (P < 0.05) in steer meat, whereas decreased the juiciness (P < 0.01) of cow meat. Regardless of the ageing method, cow meat was tougher (P < 0.0001), less juicy (P < 0.001) and sweeter (P < 0.05) and presented higher amount of perceived connective tissue (P < 0.0001) than steer meat, whereas steer meat had higher ratings for beef (P < 0.05) and brown-roasted (P < 0.01) flavours. Volatile compounds were largely affected (P < 0.05) by animal-type, most of them being higher in cow than steer meat. In contrast, in-the-bag dry-ageing affected a few volatile compounds such as alcohols, aldehydes and ketones.

Performance evaluation of the Simtomax® CoronaCheck rapid diagnostic test.

The aim of this study was to evaluate the diagnostic performance of Simtomax® CoronaCheck, a serology rapid diagnostic test (RDT) for the detection of IgG and IgM against SARS-CoV-2. 48 plasma samples positive for SARS-CoV-2 based on RT-PCR and 98 negative control samples were studied. Diagnostic performance of the IgG/IgM RDT was assessed against RT-PCR and the electro-chemiluminescence immunoassay (ECLIA) Elecsys® Anti-SARS-CoV-2 total Ig. Overall, the RDT sensitivity was 92 % (95 % confidence interval [95 %CI]: 79-97), specificity 97 % (95 % CI: 91-99 %), PPV 94 % (95 % CI: 81-98) and the NPV 96 % (95 % CI: 89-99). When considering only samples collected ≥ 15 days post-symptoms (DPS), the sensitivity increased to 98 % (95 %CI: 86-100) and the specificity was 97 % (95 % CI: 91-99 %). Two samples with 180 DPS were still positive for IgG. Globally, this IgG/IgM RDT displayed a high diagnostic accuracy for SARS-CoV-2 IgG/IgM detection in plasma samples in high COVID-19 prevalence settings. It could be effectively used, in absence of facilities for routine diagnostic serology, for samples with a DPS between 15 and 180 days.

2021 Spanish Society of Hypertension position statement about telemedicine.

The pandemic caused by coronavirus SARS-CoV-2 (COVID-19) has forced, in many cases, to replace face-to-face consultation with the telematic consultation, in order to reduce the risk of contagion associated with the presence of patients in health centres. This change may represent an opportunity for a different and more effective communication between professionals and patients, allowing better accessibility to medical care and more systematic and comprehensive approach to patients with hypertension and cardiovascular risk. However, organisational tools are needed to facilitate communication between patients and professionals, specifically with the exchange of clinical data by remote monitoring of variables associated with hypertension and cardiovascular risk (blood pressure, weight, height, blood tests…), and allow monitoring of adherence to treatments, lifestyles and risk factors. It would be desirable for this to be carried out by multidisciplinary teams, both from primary care, hospital and community pharmacy, with an adequate coordination of care. This document of the Spanish Society of Hypertension (SEH-LELHA) tries to give the keys to improve the quality of care of telematic consultations of patients with hypertension and cardiovascular risk, provide basic criteria of telematic or face to face attention and systematise their content. Likewise, the follow-up criteria are proposed by the different professionals.

Optic neuritis in paediatric patients: Experience over 27 years and a management protocol. / Neuritis óptica en pediatría: experiencia en 27 años y protocolo de actuación.

INTRODUCTION AND OBJECTIVE: In this article, we present our experience on optic neuritis (ON) and provide a diagnostic/therapeutic protocol, intended to rule out other aetiologies (particularly infection), and a fact sheet for parents. MATERIAL AND METHODS: We conducted a descriptive, retrospective study of patients with ON over a 27-year period (1990-2017). A review of the available scientific evidence was performed in order to draft the protocol and fact sheet. RESULTS: Our neuropaediatrics department has assessed 20,744 patients in the last 27 years, of whom 14 were diagnosed with ON: 8 had isolated ON, 1 had multiple sclerosis (MS), 1 had clinically isolated syndrome (CIS), 3 had acute disseminated encephalomyelitis, and 1 had isolated ON and a history of acute disseminated encephalomyelitis one year previously. Patients' age range was 4-13 years; 50% were boys. Eight patients were aged over 10: 7 had isolated ON and 1 had MS. Nine patients had bilateral ON, and 3 had retrobulbar ON. MRI results were normal in 7 patients and showed involvement of the optic nerve only in 2 patients and optic nerve involvement + central nervous system demyelination in 5. Thirteen patients received corticosteroids. One patient had been vaccinated against meningococcus-C the previous month. Progression was favourable, except in the patient with MS. A management protocol and fact sheet are provided. CONCLUSIONS: ON usually has a favourable clinical course. In children aged older than 10 years with risk factors for MS or optic neuromyelitis (hyperintensity on brain MRI, oligoclonal bands, anti-NMO antibody positivity, ON recurrence), the initiation of immunomodulatory treatment should be agreed with the neurology department. The protocol is useful for diagnostic decision-making, follow-up, and treatment of this rare disease with potentially major repercussions. The use of protocols and fact sheets is important.

Immunogenicity and Protective Efficacy of Radiation-Attenuated and Chemo-Attenuated PfSPZ Vaccines in Equatoguinean Adults.

Plasmodium falciparum sporozoite (PfSPZ) Vaccine (radiation-attenuated, aseptic, purified, cryopreserved PfSPZ) and PfSPZ-CVac (infectious, aseptic, purified, cryopreserved PfSPZ administered to subjects taking weekly chloroquine chemoprophylaxis) have shown vaccine efficacies (VEs) of 100% against homologous controlled human malaria infection (CHMI) in nonimmune adults. Plasmodium falciparum sporozoite-CVac has never been assessed against CHMI in African vaccinees. We assessed the safety, immunogenicity, and VE against homologous CHMI of three doses of 2.7 × 106 PfSPZ of PfSPZ Vaccine at 8-week intervals and three doses of 1.0 × 105 PfSPZ of PfSPZ-CVac at 4-week intervals with each arm randomized, double-blind, placebo-controlled, and conducted in parallel. There were no differences in solicited adverse events between vaccinees and normal saline controls, or between PfSPZ Vaccine and PfSPZ-CVac recipients during the 6 days after administration of investigational product. However, from days 7-13, PfSPZ-CVac recipients had significantly more AEs, probably because of Pf parasitemia. Antibody responses were 2.9 times higher in PfSPZ Vaccine recipients than PfSPZ-CVac recipients at time of CHMI. Vaccine efficacy at a median of 14 weeks after last PfSPZ-CVac dose was 55% (8 of 13, P = 0.051) and at a median of 15 weeks after last PfSPZ Vaccine dose was 27% (5 of 15, P = 0.32). The higher VE in PfSPZ-CVac recipients of 55% with a 27-fold lower dose was likely a result of later stage parasite maturation in the liver, leading to induction of cellular immunity against a greater quantity and broader array of antigens.

Authentication of barley-finished beef using visible and near infrared spectroscopy (Vis-NIRS) and different discrimination approaches.

This study evaluated visible and near-infrared spectroscopy (Vis-NIRS) to authenticate barley-finished beef using different discrimination approaches. Dietary grain source (barley, corn, or blend-50% barley/50% corn) did not affect (P > 0.05) meat quality but influenced (P < 0.05) fatty acid profiles. The longissimus thoracis (LT) from barley-fed steers had lower n-6 fatty acid content and n-6/n-3 ratio compared to LT from corn and blended grain-fed steers. Vis-NIRS coupled with partial least square discriminant analysis (PLS-DA) and support vector machine in the linear (L-SVM) kernel classified with approximately 70% overall accuracy subcutaneous fat and intact LT samples, respectively, from barley, corn, and blended-fed cattle. When only barley and corn samples were considered, fat and intact LT samples were correctly classified with overall accuracy >94% with PLS-DA and radial/L-SVM, and approximately 90% with PLS-DA and L-SVM, respectively. Ground LT samples were classified with ≤70% overall accuracy. Vis-NIRS measurements on fat and intact LT have potential to discriminate between corn and barley-fed beef.

Implementation of a Postfracture Care Program in a Private Hospital in Colombia.

PURPOSE: To describe the implementation of a postfracture care program in a private hospital in Colombia, the results achieved after the program's first year, and the challenges encountered. METHODS: A cross-sectional descriptive study of the first year's outcomes. The program was implemented following best practices described in the "Capture the Fracture" framework. We assessed the management of fractures before the launch of the program. A multidisciplinary group was established to collaborate on the diagnosis and treatment of patients with osteoporotic fractures. A full-time program coordinator was appointed. We analyzed the program's clinical outcomes and limitations. RESULTS: One-hundred and ninety patients were included in the study, with an average age of 76.7. Hip fracture was the most frequent one (33.6%). After the first year of implementing the program, 39.4% of patients received osteoporosis treatment, with an adherence rate of 73%. The incidence of subsequent falls was 5.8% and 1% for new fractures. CONCLUSIONS: The implementation of a program for patients' care with fragility fractures is challenging for healthcare institutions. The role of a full-time coordinator is critical for the proper operation of such programs.

Effect of elicitors on holm oak somatic embryo development and efficacy inducing tolerance to Phytophthora cinnamomi.

Holm oak trees (Quercus ilex L.) mortality is increasing worryingly in the Mediterranean area in the last years. To a large degree this mortality is caused by the oomycete Phytophthora spp., which is responsible for forest decline and dieback in evergreen oak forest areas of the southwestern Iberian Peninsula. This study is based on the possibility of applying chemical elicitors or filtered oomycete extracts to holm oak somatic embryos (SE) in order to induce epigenetic memory, priming, that may increase tolerance to the pathogen in future infections. To this end, we first examined the effect of priming treatments on SE development and its oxidative stress state, to avoid elicitors that may cause damage to embryogenic tissues. Both, the sterile oomycete extracts and the chemical elicitor methyl jasmonate (MeJA) did not produce any detrimental effect on SE growth and development, unlike the elicitors benzothiadiazole (BTH) and p-aminobenzoic acid (PABA) that reduced the relative weight gain and resulted in necrotic and deformed SE when were applied at high concentrations (25 µM BTH or 50 µM PABA) in accordance with their high malondialdehyde content. No significant differences among elicitation treatments were found in dual culture bioassays, although those SEs elicited with 50 µM MeJA increased H2O2 production after challenged against active oomycete indicating the activation of stress response. Since this elicitation treatment did not produce any adverse effect in the embryogenic process we suggest that could be used in further priming experiments to produce holm oak plants adapted to biotic stress.

Protein phosphatase 2A B55ß limits CD8+ T cell lifespan following cytokine withdrawal.

How T cells integrate environmental cues into signals that limit the magnitude and length of immune responses is poorly understood. Here, we provide data that demonstrate that B55ß, a regulatory subunit of protein phosphatase 2A, represents a molecular link between cytokine concentration and apoptosis in activated CD8+ T cells. Through the modulation of AKT, B55ß induced the expression of the proapoptotic molecule Hrk in response to cytokine withdrawal. Accordingly, B55ß and Hrk were both required for in vivo and in vitro contraction of activated CD8+ lymphocytes. We show that this process plays a role during clonal contraction, establishment of immune memory, and preservation of peripheral tolerance. This regulatory pathway may represent an unexplored opportunity to end unwanted immune responses or to promote immune memory.

Correction to: Stingray spear injury to the pediatric spinal cord: case report and review of the literature.

The original version of this article unfortunately contained an error in the spelling of the last name of one of the co-authors. The corresponding author did not notice that the last name of one of the co-authors, Nathan Shlobin, was misspelled as "Schlobin". The correct spelling of his last name is "Shlobin". Given in this article is the corrected author name.

[Atypical presentation of early childhood epileptic encephalopathy associated with the gene KCNT1]. / Presentación atípica de encefalopatía epiléptica infantil precoz asociada al gen KCNT1.

TITLE: Presentación atípica de encefalopatía epiléptica infantil precoz asociada al gen KCNT1.

Stingray spear injury to the pediatric spinal cord: case report and review of the literature.

Stingray injuries are rare, mostly causing injuries to the lower extremities but occasionally fatal if there is direct puncture of the thorax, abdomen, or neck. Direct combined stingray injury to the central nervous system has not been reported in the literature. Herein we present the case of a 12-year-old boy who, while wading at the seashore of the Costa Rica's Pacific Ocean, sustained a combined oblique penetrating injury to the C6 vertebra caused by a Stingray. He initially presented to the hospital with a complete asymmetric right C6/left T1 ASIA A examination, priapism, and loss of anal sphincter tone. Imaging revealed fracture of the posterior elements of C6 with an oblique trajectory into the left radicular foramen. T2W images did not reveal anatomical section but rather edema and minor bleeding in the epidural space. The patient underwent medical management and serial imaging. During the next 3 months, there was recovery of sensation on the right hemi body, bilateral paresthesias and asymmetric progressive improvement in strength on both legs. Acute care management and midterm term follow up are provided, along with a review of the literature for salient management considerations when evaluating and treating combined penetrating and envenomation injuries caused by stingrays. To our knowledge, this is the first report of such injury to the spine.

[Familial MECP2 duplication syndrome]. / Síndrome de duplicación MECP2 familiar.

TITLE: Síndrome de duplicación MECP2 familiar.