CandeSpartan Study: Candesartan Spanish Response-prediction and Tolerability study in migraine.

INTRODUCTION: Effectiveness of candesartan in migraine prevention is supported by two randomized controlled trials. We aimed to assess the effectiveness, tolerability, and response predictors of candesartan in the preventive treatment of migraine. METHODS: Observational, multicenter, prospective cohort study. The 50%, 75% and 30% responder rates, between weeks 8-12 and 20-24, were compared with the baseline. Treatment emergent adverse effects were systematically evaluated. Response predictors were estimated by multivariate regression models. RESULTS: Eighty-six patients were included, 79.1% females, aged 39.5 (inter-quartile range [IQR] 26.3-50.3), with chronic migraine (43.0%), medication overuse headache (55.8%) and a median of two (inter-quartile range: 0.75-3) prior preventive treatments. At baseline patients had 14 (10-24) headache and 8 (5-11) migraine days per month. The 30%, 50% and 75% responder rates were 40%, 34.9% and 15.1% between weeks 8-12, and 48.8%, 36%, and 18.6% between weeks 20-24. Adverse effects were reported by 30 (34.9%) and 13 (15.1%) patients between weeks 0-12 and 12-24, leading to discontinuation in 15 (17.4%) patients. Chronic migraine, depression, headache days per month, medication overuse headache, and daily headache at baseline predicted the response between weeks 20-24. CONCLUSION: Candesartan effectiveness and tolerability in migraine prevention was in line with the clinical trials' efficacy.Trial registration: The study protocol is registered in ClinicalTrials.gov (NCT04138316).

Evaluation of the potential therapeutic benefits of macrophage reprogramming in multiple myeloma.

Tumor-associated macrophages (TAM) are important components of the multiple myeloma (MM) microenvironment that support malignant plasma cell survival and resistance to therapy. It has been proposed that macrophages (MØ) retain the capacity to change in response to stimuli that can restore their antitumor functions. Here, we investigated several approaches to reprogram MØ as a novel therapeutic strategy in MM. First, we found tumor-limiting and tumor-supporting capabilities for monocyte-derived M1-like MØ and M2-like MØ, respectively, when mixed with MM cells, both in vitro and in vivo. Multicolor confocal microscopy revealed that MM-associated MØ displayed a predominant M2-like phenotype in the bone marrow of MM patient samples, and a high expression of the pro-M2 cytokine macrophage migration inhibitory factor (MIF). To reprogram the protumoral M2-like MØ present in MM toward antitumoral M1-like MØ, we tested the pro-M1 cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) plus blockade of the M2 cytokines macrophage colony-stimulating factor or MIF. The combination of GM-CSF plus the MIF inhibitor 4-iodo-6-phenyl-pyrimidine achieved the best reprogramming responses toward an M1 profile, at both gene and protein expression levels, as well as remarkable tumoricidal effects. Furthermore, this combined treatment elicited MØ-dependent therapeutic responses in MM xenograft mouse models, which were linked to upregulation of M1 and reciprocal downregulation of M2 MØ markers. Our results reveal the therapeutic potential of reprogramming MØ in the context of MM.

Crestal bone loss around submerged and non-submerged implants during the osseointegration phase with different healing abutment designs: a randomized prospective clinical study.

OBJECTIVE: To evaluate peri-implant crestal bone loss during the osseointegration period, comparing submerged and non-submerged implants with healing abutments of different design. MATERIALS AND METHODS: A total of 90 Avinent®  dental implants (Avinent Implant System, Barcelona, Spain) were placed in 90 patients. All were sited in the posterior mandibular zone to replace teeth 3.6 or 4.6. Patients were divided randomly into three groups: submerged (n = 30), non-submerged with anatomical healing abutment (n = 30), and non-submerged with esthetic healing abutment (n = 30). Peri-implant crestal bone loss was evaluated in intraoral radiographs taken at baseline, 1, and 3 months after implant placement. RESULTS: Peri-implant crestal bone loss at the end of the (3-month) osseointegration period was lowest in the submerged group (0.11 ± 0.14 mm), followed by the esthetic non-submerged group (0.15 ± 0.06 mm), but without statistically significant difference between these groups (P = 0.234). The greatest bone loss was produced in the non-submerged group with anatomical healing abutments (0.37 ± 0.12 mm), with significant differences between this group and the other two (P < 0.001). CONCLUSIONS: On the basis of these findings, bone resorption during the osseointegration period using the non-submerged technique varied significantly depending on the morphology of the healing abutment used. The non-submerged technique with an esthetic healing post-produced an equally predictable outcome compared with the submerged technique.

Periodontal disease as a risk factor of recurrence of venous thromboembolic disease: a prospective study.

BACKGROUND: In recent years, periodontal disease has been related to a large number of systemic disorders. OBJECTIVE: To study the possible relationship between periodontal disease and high levels of D-dimer in a group of patients with venous thromboembolic disease. MATERIALS AND METHODS: A study was made of 142 patients diagnosed with unprovoked venous thromboembolic disease. All patients underwent oral examination consecutively and randomly. Finally, two groups were obtained: (a) patients with periodontal disease (n = 71); and (b) patients without periodontal disease (n = 71). All patients were subjected to periodontal study, with evaluation of the number of teeth, bleeding index, gingival index, simplified oral hygiene index, community periodontal index of treatment needs, clinical attachment level, probe depth, number of pockets ≥4 mm, number of pockets ≥6 mm. The D-dimer values were evaluated in both groups. RESULTS: D-dimer values were higher in the study group than the control group, with statistically significant differences (p = 0.010). CONCLUSIONS: A relationship is observed between the presence of periodontal disease and high D-dimer levels. Patients with venous thromboembolic disease and periodontal disease could have more risk of a new thromboembolism episode.

Troubled adolescents: substance abuse and mental disorder in young offenders.

INTRODUCTION: Many studies indicate the high prevalence of juvenile substance abuse. There is increasingly more dual diagnosis and mental illnesses in adolescents and many juvenile offenses are related to drug abuse. METHOD: This is a descriptive study about the relationship between drug abuse and clinical, demographic and criminal characteristics in a sample of 144 youths seen in the Therapeutic Juvenile Justice Unit (UTJJ) of the Parc Sanitari Sant Joan de Deu. RESULTS: A total of 65.3% of the sample had a disorder on Axis I, 22.2% of which were related with the psychotic spectrum and 18.1% ADHD. Personality disorder occurred in 42.4%, the most frequent ones being antisocial disorder (16%), and borderline personality disorder (6.9%). Of the sample, 78.5% were drug consumers and 51.4% of the total only consumed 1 substance. There is a tendency among psychotic teenagers to consume cannabis and ADHD patients to consume cannabis and cocaine. A significant relationship is found between nationality and inhalants drugs, social and economic level and sedative drugs and alcohol, and parental death and alcohol (p<0.05-0.005). CONCLUSIONS: The level of drug use/abuse in juvenile justice is very high. Although there is no evidence about the relationship between the substance they consume and the profile of the young offender, some tendencies are observed.

Diversity of bladed Bangiales (Rhodophyta) in western Mediterranean: recognition of the genus Themis and descriptions of T. ballesterosii sp. nov., T. iberica sp. nov., and Pyropia parva sp. nov.

The diversity of the bladed species of the red algal order Bangiales from the Iberian Mediterranean shores has been reassessed after a detailed study of this region. Prior to this study, 11 bladed species of Bangiales had been reported from Mediterranean waters: Porphyra atropurpurea, P. cordata, P. coriacea, P. dioica, P. linearis, P. purpurea, P. umbilicalis, Pyropia leucosticta, Pyropia koreana (as P. olivii), Py. elongata (as P. rosengurttii) and Py. suborbiculata. A combined analysis of the nuclear nSSU and the plastid rbcL genes together with detailed morphological studies has confirmed the presence of species within the genera Porphyra and Pyropia and also revealed a third, undescribed genus, Themis gen. nov. Porphyra linearis, Pyropia elongata and the introduced Pyropia koreana had been previously listed for the Mediterranean and were recorded in this study. An additional four species, including the introduced Pyropia suborbiculata and three new species: Pyropia parva sp. nov., Themis ballesterosii sp. nov., and Themis iberica sp. nov. were also observed. Hence, most of the Porphyra species traditionally reported along these shores were not reported in this survey. This new floristic Bangiales composition confirms the importance of the Mediterranean basin as a hotspot for biodiversity, possible endemics of ancient origin and high proportion of introductions. Our data also continue to confirm the extent of Bangiales diversity at regional and worldwide levels.

Keratocystic odontogenic tumor. Case report and review of the literature.

Keratocystic odontogenic tumor is an intraosseous benign tumor of epithelial origin that can appear as a unicystic or multicystic lesion. It is characterized most significantly by its high recurrence rate. This is why surgical removal is the chosen therapeutic approach in most cases. However, while surgery may be the safest technique to prevent recidivism, it may also result in numerous complications with large tumors. A number of authors have suggested a more conservative treatment for large keratocystic odontogenic tumors. The case examined in this article is that of a 48-year-old male patient who presented with a five-month swelling on the left side of his face, located in the mandibular area.

Corrigendum: Editorial: Cross-talk between heterogeneous cell types in skeletal muscle: implications for glucose metabolism.

[This corrects the article DOI: 10.3389/fendo.2023.1185725.].

Vitamin D deficiency and SARS­CoV­2 infection: A retrospective case-Control study with big-data analysis covering March 2020 to March 2021.

BACKGROUND: Vitamin D may have immunomodulatory functions, and might therefore play a role in the pathogenesis of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, no conclusive evidence exists regarding its impact on the prevalence of this infection, the associated course of disease, or prognosis. OBJECTIVE: To study the association between SARS-CoV-2 infection and vitamin D deficiency in patients attending a tertiary university hospital, and to examine the clinical course of infection and prognosis for these patients. METHODS: This non-interventional, retrospective study, which involved big-data analysis and employed artificial intelligence to capture data from free text in the electronic health records of patients diagnosed with SARS-CoV-2, was undertaken at a tertiary university hospital in Madrid, Spain, between March 2020 and March 2021. The variables recorded were vitamin D deficiency, sociodemographic and clinical characteristics, course of disease, and prognosis. RESULTS: Of the 143,157 patients analysed, 36,261 had SARS-CoV-2 infection (25.33%) during the study period, among whom 2,588 (7.14%) had a vitamin D deficiency. Among these latter patients, women (OR 1.45 [95%CI 1.33-1.57]), adults over 80 years of age (OR 2.63 [95%CI 2.38-2.91]), people living in nursing homes (OR 2.88 [95%CI 2.95-3.45]), and patients with walking dependence (OR 3.45 [95%CI 2.85-4.26]) appeared in higher proportion. After adjusting for confounding factors, a higher proportion of subjects with SARS-CoV-2 plus vitamin D deficiency required hospitalisation (OR 1.38 [95%CI 1.26-1.51]), and had a longer mean hospital stay (3.94 compared to 2.19 days in those with normal levels; P = 0.02). CONCLUSION: A low serum 25(OH) vitamin D concentration in patients with SARS-CoV-2 infection is significantly associated with a greater risk of hospitalisation and a longer hospital stay. Among such patients, higher proportions of institutionalised and dependent people over 80 years of age were detected.

The transcriptional control of the VEGFA-VEGFR1 (FLT1) axis in alternatively polarized murine and human macrophages.

Introduction: Macrophages significantly contribute to the regulation of vessel formation under physiological and pathological conditions. Although the angiogenesis-regulating role of alternatively polarized macrophages is quite controversial, a growing number of evidence shows that they can participate in the later phases of angiogenesis, including vessel sprouting and remodeling or regression. However, the epigenetic and transcriptional regulatory mechanisms controlling this angiogenesis-modulating program are not fully understood. Results: Here we show that IL-4 can coordinately regulate the VEGFA-VEGFR1 (FLT1) axis via simultaneously inhibiting the proangiogenic Vegfa and inducing the antiangiogenic Flt1 expression in murine bone marrow-derived macrophages, which leads to the attenuated proangiogenic activity of alternatively polarized macrophages. The IL-4-activated STAT6 and IL-4-STAT6 signaling pathway-induced EGR2 transcription factors play a direct role in the transcriptional regulation of the Vegfa-Flt1 axis. We demonstrated that this phenomenon is not restricted to the murine bone marrow-derived macrophages, but can also be observed in different murine tissue-resident macrophages ex vivo and parasites-elicited macrophages in vivo with minor cell type-specific differences. Furthermore, IL-4 exposure can modulate the hypoxic response of genes in both murine and human macrophages leading to a blunted Vegfa/VEGFA and synergistically induced Flt1/FLT1 expression. Discussion: Our findings establish that the IL-4-activated epigenetic and transcriptional program can determine angiogenesis-regulating properties in alternatively polarized macrophages under normoxic and hypoxic conditions.

Abundance and composition of epiphytic bacterial and archaeal ammonia oxidizers of marine red and brown macroalgae.

Ammonia-oxidizing bacteria (AOB) and archaea (AOA) are important for nitrogen cycling in marine ecosystems. Little is known about the diversity and abundance of these organisms on the surface of marine macroalgae, despite the algae's potential importance to create surfaces and local oxygen-rich environments supporting ammonia oxidation at depths with low dissolved oxygen levels. We determined the abundance and composition of the epiphytic bacterial and archaeal ammonia-oxidizing communities on three species of macroalgae, Osmundaria volubilis, Phyllophora crispa, and Laminaria rodriguezii, from the Balearic Islands (western Mediterranean Sea). Quantitative PCR of bacterial and archaeal 16S rRNA and amoA genes was performed. In contrast to what has been shown for most other marine environments, the macroalgae's surfaces were dominated by bacterial amoA genes rather than those from the archaeal counterpart. On the basis of the sequences retrieved from AOB and AOA amoA gene clone libraries from each algal species, the bacterial ammonia-oxidizing communities were related to Nitrosospira spp. and to Nitrosomonas europaea and only 6 out of 15 operational taxonomic units (OTUs) were specific for the host species. Conversely, the AOA diversity was higher (43 OTUs) and algal species specific, with 17 OTUs specific for L. rodriguezii, 3 for O. volubilis, and 9 for P. crispa. Altogether, the results suggest that marine macroalgae may exert an ecological niche for AOB in marine environments, potentially through specific microbe-host interactions.

Postnatal testicular development in mouse species with different levels of sperm competition.

Postcopulatory sexual selection leads to an increase in sperm numbers which is partly the result of an increase in relative testes mass and could also be the consequence of changes in testis architecture or function. Very little is known regarding developmental changes during the first spermatogenic wave that may lead to enhanced spermatogenic efficiency and increased sperm production. We examined testicular development after birth in four mouse species with different sperm competition levels to assess changes in testicular architecture and function. Differences in relative testes mass between species appeared soon after birth and were exacerbated thereafter. The volume of testes occupied by seminiferous tubules differed between species postnatally and were associated with sperm competition levels. Finally, changes over time in the proportions of tubules with different germ cell types were also associated with sperm competition levels, with the time taken for the transition between various cell stages being negatively associated with levels of sperm competition. We conclude that postnatal testis development differs between closely related species with different sperm competition levels influencing testis architecture and the rate of progression of spermatogenesis, leading to differences in testis function at reproductive maturity.

Evaluation of the viasure Neisseria gonorrhoeae ciprofloxacin resistant assay for the simultaneous identification and direct detection of ciprofloxacin susceptibility.

The detection of resistance without the need for culture is essential to establish a guided treatment against Neisseria gonorrhoeae (NG) infections. We evaluated the VIASURE Neisseria gonorrhoeae ciprofloxacin resistant Real Time PCR Detection Kit (CerTest Biotec S.L, Zaragoza, Spain) for the simultaneous identification and direct detection of ciprofloxacin susceptibility in 88 NG isolates and 133 positive NG clinical samples of different anatomical location. The sensitivity for NG detection was 93.2% and the specificity 100%. The sensitivity of the test to characterize resistance/susceptibility to ciprofloxacin was (96.5%). In conclusion, the test evaluated is suitable for use to establish a targeted therapy with oral ciprofloxacin in case of not detecting resistance.

Regenerative inflammation: When immune cells help to re-build tissues.

Inflammation is an essential immune response critical for responding to infection, injury and maintenance of tissue homeostasis. Upon injury, regenerative inflammation promotes tissue repair by a timed and coordinated infiltration of diverse cell types and the secretion of growth factors, cytokines and lipids mediators. Remarkably, throughout evolution as well as mammalian development, this type of physiological inflammation is highly associated with immunosuppression. For instance, regenerative inflammation is the consequence of an in situ macrophage polarization resulting in a transition from pro-inflammatory to anti-inflammatory/pro-regenerative response. Immune cells are the first responders upon injury, infiltrating the damaged tissue and initiating a pro-inflammatory response depleting cell debris and necrotic cells. After phagocytosis, macrophages undergo multiple coordinated metabolic and transcriptional changes allowing the transition and dictating the initiation of the regenerative phase. Differences between a highly efficient, complete ad integrum tissue repair, such as, acute skeletal muscle injury, and insufficient regenerative inflammation, as the one developing in Duchenne Muscular Dystrophy (DMD), highlight the importance of a coordinated response orchestrated by immune cells. During regenerative inflammation, these cells interact with others and alter the niche, affecting the character of inflammation itself and, therefore, the progression of tissue repair. Comparing acute muscle injury and chronic inflammation in DMD, we review how the same cells and molecules in different numbers, concentration and timing contribute to very different outcomes. Thus, it is important to understand and identify the distinct functions and secreted molecules of macrophages, and potentially other immune cells, during tissue repair, and the contributors to the macrophage switch leveraging this knowledge in treating diseases.

Antibody Response Induced by BNT162b2 and mRNA-1273 Vaccines against the SARS-CoV-2 in a Cohort of Healthcare Workers.

The aim of this study was to characterize the antibody response induced by SARS-CoV-2 mRNA vaccines in a cohort of healthcare workers. A total of 2247 serum samples were analyzed using the Elecsys® Anti-SARS-CoV-2 S-test (Roche Diagnostics International Ltd., Rotkreuz, Switzerland). Sex, age, body mass index (BMI), arterial hypertension, smoking and time between infection and/or vaccination and serology were considered the confounding factors. Regarding the medians, subjects previously infected with SARS-CoV-2 who preserved their response to the nucleocapsid (N) protein showed higher humoral immunogenicity (BNT162b2: 6456.0 U/mL median; mRNA-1273: 2505.0 U/mL) compared with non-infected (BNT162b2: 867.0 U/mL; mRNA-1273: 2300.5 U/mL) and infected subjects with a lost response to N protein (BNT162b2: 2992.0 U/mL). After controlling for the confounders, a higher response was still observed for mRNA-1273 compared with BNT162b2 in uninfected individuals (FC = 2.35, p < 0.0001) but not in previously infected subjects (1.11 FC, p = 0.1862). The lowest levels of antibodies were detected in previously infected non-vaccinated individuals (39.4 U/mL). Clinical variables previously linked to poor prognoses regarding SARS-CoV-2 infection, such as age, BMI and arterial hypertension, were positively associated with increasing levels of anti-S protein antibody exclusively in infected subjects. The mRNA-1273 vaccine generated a higher antibody response to the S protein than BNT162b2 in non-infected subjects only.

Topical tacrolimus and pimecrolimus in the treatment of oral lichen planus: an update.

BACKGROUND: The search for new drugs capable of controlling the symptoms and signs of oral lichen planus (OLP) with minimal side-effects remains an important challenge. OBJECTIVE: A literature review is made to evaluate the effectiveness and safety of topical tacrolimus and pimecrolimus in the treatment of OLP. MATERIAL AND METHOD: A review was made of the studies published between 1999 and 2008 in relation to the topical application of tacrolimus and pimecrolimus in OLP. RESULTS: The data obtained point to the need for larger randomized, placebo-controlled studies with carefully selected and standardized endpoints, to allow adequate comparison between treatments. The adverse effects were fundamentally of a local nature, and in particular included burning sensation in the application zone. All the studies consulted found the treatment to be effective over short periods of time, with lesion recurrences after suppression of the drug. The long-term safety remains to be established. CONCLUSION: There is need for larger placebo-controlled, randomized studies with carefully selected and standardized outcome measures.

Comparison of the PU.1 transcriptional regulome and interactome in human and mouse inflammatory dendritic cells.

Dendritic cells (DCs) are key immune modulators and are able to mount immune responses or tolerance. DC differentiation and activation imply a plethora of molecular and cellular responses, including transcriptional changes. PU.1 is a highly expressed transcription factor in DCs and coordinates relevant aspects of DC biology. Due to their role as immune regulators, DCs pose as a promising immunotherapy tool. However, some of their functional features, such as survival, activation, or migration, are compromised due to the limitations to simulate in vitro the physiologic DC differentiation process. A better knowledge of transcriptional programs would allow the identification of potential targets for manipulation with the aim of obtaining "qualified" DCs for immunotherapy purposes. Most of the current knowledge regarding DC biology derives from studies using mouse models, which not always find a parallel in human. In the present study, we dissect the PU.1 transcriptional regulome and interactome in mouse and human DCs, in the steady state or LPS activated. The PU.1 transcriptional regulome was identified by performing PU.1 chromatin immunoprecipitation followed by high-throughput sequencing and pairing these data with RNAsequencing data. The PU.1 interactome was identified by performing PU.1 immunoprecipitation followed by mass spectrometry analysis. Our results portray PU.1 as a pivotal factor that plays an important role in the regulation of genes required for proper DC activation and function, and assures the repression of nonlineage genes. The interspecies differences between human and mouse DCs are surprisingly substantial, highlighting the need to study the biology of human DCs.

Long-term evaluation of quality of life and satisfaction between implant bar overdentures and conventional complete dentures: A 23 years retrospective study.

BACKGROUND: Dental implants have been used in edentulous jaws to improve the retention and stability of complete dentures. Attachment to the implants improves stability and function of the prostheses and increases patient satisfaction. PURPOSE: The aim of this study was to evaluate quality of life and satisfaction between patients with implant overdentures and complete dentures for more than 20 years. METHODS: Forty patients with overdentures and 40 patients with conventional complete dentures were included in this study. Both groups are carriers of their prosthesis more than 20 years. All patients completed an OHIP-14 and perception and satisfaction questionnaire related their implant prothesis. RESULTS: Follow-up mean in patients with overdentures were 23.27 ± 1.87 years and 23.20 ± 3.91 years for conventional prosthesis group. A worse quality of life was shown in the group of patients with conventional dentures in the 7 dimensions and in the total value, with statistically significant differences in 6 dimensions and in the total value (P ≤ .05). Patients with implants overdenture were more satisfied than patients with conventional dentures, with statistically significant differences (P < .001). CONCLUSIONS: Implant overdentures on cobalt chrome and gold bars offer an excellent long-term solution for edentulism compared with conventional denture.

Prevalence of rheumatoid cachexia assessed by bioelectrical impedance vector analysis and its relation with physical function.

Rheumatoid arthritis (RA) patients frequently have changes in their body composition, with a decrease in muscle mass and an increase in fat mass, a syndrome that is termed rheumatoid cachexia (RC). The prevalence of this nutritional alteration is not well known; there is as yet no consensus, seeing as it depends on the methods, techniques, and cutoff points that are used for its diagnosis. The main aim of this study was to identify RC through assessment by bioelectrical impedance vector analysis (BIVA) and its association with metabolic causes, physical function, and the main disease status, among others. The prevalence of RC was identified in those subjects who fell outside the right lower quadrant of the reference curve of RXc graph of BIVA. Clinical, anthropometric, biochemical and physical activity, emotional status, and diet markers were also evaluated. Ninety-four patients were included (92.55% women). The prevalence of RC assessed by BIVA was 21.28%. BIVA-cachexia patients had a lesser value of handgrip strength vs. patients without BIVA-cachexia 10.2 kg (7.2-13.4) vs. 14.7 kg (9.6-19), p = 0.0062. Disability and folic acid with methotrexate consumption are related to BIVA-cachexia ((OR 4.69, 95% CI 1.33, 16.54, p = 0.016) and (OR 0.19, 95%CI 0.058, 0.651, p = 0.008), respectively). BIVA could represent a valuable tool to assess presence of RC. It is important that RA patients have physical therapy to improve their nutritional status.