Changes in holopelagic Sargassum spp. biomass composition across an unusual year.

The year 2021 marked a decade of holopelagic sargassum (morphotypes Sargassum natans I and VIII, and Sargassum fluitans III) stranding on the Caribbean and West African coasts. Beaching of millions of tons of sargassum negatively impacts coastal ecosystems, economies, and human health. Additionally, the La Soufrière volcano erupted in St. Vincent in April 2021, at the start of the sargassum season. We investigated potential monthly variations in morphotype abundance and biomass composition of sargassum harvested in Jamaica and assessed the influence of processing methods (shade-drying vs. frozen samples) and of volcanic ash exposure on biochemical and elemental components. S. fluitans III was the most abundant morphotype across the year. Limited monthly variations were observed for key brown algal components (phlorotannins, fucoxanthin, and alginate). Shade-drying did not significantly alter the contents of proteins but affected levels of phlorotannins, fucoxanthin, mannitol, and alginate. Simulation of sargassum and volcanic ash drift combined with age statistics suggested that sargassum potentially shared the surface layer with ash for ~50 d, approximately 100 d before stranding in Jamaica. Integrated elemental analysis of volcanic ash, ambient seawater, and sargassum biomass showed that algae harvested from August had accumulated P, Al, Fe, Mn, Zn, and Ni, probably from the ash, and contained less As. This ash fingerprint confirmed the geographical origin and drift timescale of sargassum. Since environmental conditions and processing methods influence biomass composition, efforts should continue to improve understanding, forecasting, monitoring, and valorizing sargassum, particularly as strandings of sargassum show no sign of abating.

CADA-PRO: A Patient Questionnaire Measuring Key Cognitive, Motor, Emotional, and Behavioral Outcomes in CADASIL.

BACKGROUND: Cerebral small vessel disease (cSVD) of ischemic type, either sporadic or genetic, as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), can impact the quality of daily life on various cognitive, motor, emotional, or behavioral aspects. No instrument has been developed to measure these outcomes from the patient's perspective. We thus aimed to develop and validate a patient-reported questionnaire. METHODS: In a development study, 79 items were generated by consensus between patients, family representatives, and cSVD experts. A first sample of patients allowed assessing the feasibility (missing data, floor and ceiling effect, and acceptability), internal consistency, and dimensionality of a first set of items. Thereafter, in a validation study, we tested a reduced version of the item set in a larger sample to assess the feasibility, internal consistency, dimensionality, test-retest reliability, concurrent validity, and sensitivity to change. RESULTS: The scale was developed in 44 patients with cSVD and validated in a second sample of 89 individuals (including 43 patients with CADASIL and 46 with another cSVD). The final CADASIL Patient-Reported Outcome scale comprised 18 items covering 4 categories of consequences (depression/anxiety, attention/executive functions, motor, and daily activities) of the disease. The proportion of missing data was low, and no item displayed a major floor or ceiling effect. Both the internal consistency and test-retest reliability were good (Cronbach alpha=0.95, intraclass correlation coefficient=0.88). In patients with CADASIL, CADASIL Patient-Reported Outcome scores correlated with the modified Rankin Scale, Starkstein Apathy Scale, Hospital Anxiety and Depression scale, Working Memory Index, and trail making test times. In patients with other cSVDs, CADASIL Patient-Reported Outcome correlated only with Hospital Anxiety and Depression scale and Starkstein Apathy Scale. CONCLUSIONS: The CADASIL Patient-Reported Outcome may be an innovative instrument for measuring patient-reported outcomes in future cSVD trials. Full validation was obtained for its use in patients with CADASIL, but further improvement is needed for its application in other cSVDs.

Exploratory analysis of new craniometric measures for the investigation of biological sex using open-access statistical and machine-learning tools on a cone-beam computed tomography sample.

Investigation of the biological sex of human remains is a crucial aspect of physical anthropology. However, due to varying states of skeletal preservation, multiple approaches and structures of interest need to be explored. This research aims to investigate the potential use of distances between bifrontal breadth (FMB), infraorbital foramina distance (IOD), nasal breadth (NLB), inter-canine width (ICD), and distance between mental foramina (MFD) for combined sex prediction through traditional statistical methods and through open-access machine-learning tools. Ethical approval was obtained from the ethics committee, and out of 100 cone beam computed tomography (CBCT) scans, 54 individuals were selected with all the points visible. Ten extra exams were chosen to test the predictors developed from the learning sample. Descriptive analysis of measurements, standard deviation, and standard error were obtained. T-student and Mann-Whitney tests were utilized to assess the sex differences within the variables. A logistic regression equation was developed and tested for the investigation of the biological sex as well as decision trees, random forest, and artificial neural networks machine-learning models. The results indicate a strong correlation between the measurements and the sex of individuals. When combined, the measurements were able to predict sex using a regression formula or machine learning based models which can be exported and added to software or webpages. Considering the methods, the estimations showed an accuracy rate superior to 80% for males and 82% for females. All skulls in the test sample were accurately predicted by both statistical and machine-learning models. This exploratory study successfully established a correlation between facial measurements and the sex of individuals, validating the prediction potential of machine learning, augmenting the investigative tools available to experts with a high differentiation potential.

Brain magnetic resonance imaging lesion load at diagnosis, severity at onset and outcomes in Susac syndrome: A prospective cohort study.

BACKGROUND: Susac syndrome (SuS) is a rare occlusive microvessel disease of the brain, retina and inner ear. We aimed to determine whether brain lesion load at the acute phase predicts poor outcomes in SuS. METHODS: A prospective national cohort study was conducted from December 2012 to December 2019 in 20 centres in France. Patients included at the principal investigator's center with available brain magnetic resonance imaging (MRI) at diagnosis were analyzed. MRI was reviewed by an experienced neuroradiologist blinded to clinical status. The size, topography and number of hyperintense lesions on diffusion-weighted imaging (DWI-HL) were analyzed at diagnosis and during follow-up. Outcomes involved descriptive characteristics of patients at onset and last follow-up. RESULTS: Twenty-three patients (38.1 [18.8-56.5] years, 16 females) were prospectively studied. The triad (i.e., brain, eye and ear involvement) was complete at onset in 17 patients. Brain MRI was performed 1.1 (0.1-3.4) months after the first symptom. All patients had DWI-HL at the acute phase. Patients were separated into two groups according to the number of DWI-HL on first MRI: a first group of patients (n=15) displaying low brain lesion load (<50 DWI-HL per patient) and a second group of patients (n=8) displaying high brain lesion load (≥100 DWI-HL). The median follow-up was 57.9 (9.7-98) months. Clinical features, treatment, relapse rate, time to disappearance of DWI-HL, disabilities and professional outcome did not differ according to brain lesion load. CONCLUSION: Brain lesion load assessed by DWI at the acute phase is not associated with risks of disability in SuS.

Computer vision coaching microsurgical laboratory training: PRIME (Proficiency Index in Microsurgical Education) proof of concept.

Computer vision (CV) feedback could be aimed as a constant tutor to guide ones proficiency during microsurgical practice in controlled environments. Five neurosurgeons with different levels of microsurgical expertise performed simulated vessel dissection and micro-suture in an ex vivo model for posterior computer analysis of recorded videos. A computer program called PRIME (Proficiency Index of Microsurgical Education) used in this research recognized color-labeled surgical instruments, from downloading videos into a platform, with a range of motion greater than 3 mm, for objective evaluation of number of right and left hand movements. A proficiency index of 0 to 1 was pre-established in order to evaluate continuous training improvement. PRIME computer program captured all hand movements executed by participants, except for small tremors or inconsistencies that have a range of motion inferior to 3 mm. Number of left and right hand movements were graphically expressed in order to guide more objective and efficacious training for each trainee, without requiring body sensors and cameras around the operating table. Participants with previous microsurgical experience showed improvement from 0.2 to 0.6 (p < 0.05), while novices had no improvement. Proficiency index set by CV was suggested, in a self-challenge and self-coaching manner. PRIME would offer the capability of constant laboratory microsurgical practice feedback under CV guidance, opening a new window for oriented training without a tutor or specific apparatus regarding all levels of microsurgical proficiency. Prospective, large data study is needed to confirm this hypothesis.

p-synephrine induces transcriptional changes via the cAMP/PKA pathway but not cytotoxicity or mutagenicity in human gastrointestinal cells.

p-Synephrine (SN) is an alkaloid added to thermogenic formulations for weight loss that is predominantly absorbed in the human gastrointestinal tract (GI). As the adverse effects of SN on GI cells remain unclear, the aim of present study was to examine whether SN affected cell viability, cell cycle kinetics, genomic stability, redox status, and expression of cAMP/PKA pathway genes related to metabolism/energy homeostasis in stomach mucosa (MNP01) and colon adenocarcinoma (Caco-2) human cells. p-Synephrine at 25-5000 µM was not cytotoxic to both cell lines. At 2-200 µM, SN increased the formation of reactive oxygen species (ROS) but also enhanced levels of antioxidant defense molecules glutathione (GSH) and catalase (CAT) activity, which may account for the absence of cytotoxicity/mutagenicity in both cell lines. SN induced expression of the cAMP/PKA pathway genes ADCY3 and MAPK1 in MNP01 cells and MAPK1, GNAS, PRKACA, and PRKAR2A in Caco-2 cells, as well as modulated the transcription of genes related to cell proliferation (JUN; AKT1) and inflammation (RELA; TNF) in both cell lines. Therefore, the improved antioxidant state mitigated pro-oxidative effects attributed to SN. Evidence indicates that SN does not appear to exhibit adverse potential but modulated the cAMP/PKA pathway in human GI cell lines.

Efficacy of Minoxidil Combined With Photobiomodulation for the Treatment of Male Androgenetic Alopecia. A Double-Blind Half-Head Controlled Trial.

BACKGROUND: Androgenetic alopecia (AGA) is a hair loss disorder that frequently affects the male population. Conventional treatment modalities are limited to minoxidil, 5α reductase inhibitors, and hair transplantation procedures. The efficacy of low-level laser therapy (LLLT), also known as photobiomodulation, in the treatment of AGA has been reported, yet little is known about the outcomes of combining photobiomodulation with other conventional therapies. OBJECTIVE: To evaluate hair growth improvement in males with AGA, during the administration of minoxidil with and without photobiomodulation, using a half-head model. STUDY DESIGN/MATERIALS AND METHODS: Twenty-one men with AGA agreed to undergo 12 minutes of low-level laser irradiation (using a modified Capellux®), followed by topical minoxidil application (1 ml of 5% solution), to the affected scalp two times per day for 6 months. The photobiomodulation devices were modified such that the left half emitted light, and the right half did not. Efficacy was assessed by blinded analyses of clinical photos and automated phototrichograms (Trichoscan®) taken before treatment and after 3 and 6 months of therapy. RESULTS: None of the study participants experienced any adverse events. All patients showed improvements in hair coverage on both sides of the scalp at 3 and 6 months. On the side with combined treatments, the number of total hairs was significantly increased after 3 (P < 0.001) and 6 months (P = 0.001). A similar increase was also observed on the minoxidil-only side, at both 3 (P < 0.001) and 6 months (P < 0.001). No statistically significant differences were detected between sides (P > 0.05). CONCLUSION: Additional improvement was not observed with the association of photobiomodulation to topical minoxidil in male AGA. Differences from previous studies that might have influenced our result include non-collimated light source, higher dosimetry, and a cohort with darker skin phototype and more severe alopecia. Lasers Surg. Med. 2021. © 2021 Wiley Periodicals LLC.

Reconstruction of Acetabular Defects With Impaction Grafting in Primary Cemented Total Hip Arthroplasty Produces Favorable Results: Clinical and Radiographic Outcomes Over 6.4 Years on Average.

BACKGROUND: Cemented primary total hip arthroplasty (THA) associated with acetabular reconstruction (AR) involving impacted bone grafting has been employed successfully in the revision of cavitary defects but the results are reportedly less predictable for segmental defects. The objective of the study is to evaluate the clinical and radiographic results of patients who had presented cavitary, segmental, and combined acetabular defects and received THA/AR involving impacted morselized cancellous bone autografts followed by rigorous postoperative management. METHODS: Clinical outcomes were assessed retrospectively of 154 patients who had been submitted to 169 THA/AR procedures performed by a single surgeon over a 15-year period. The Harris Hip Score system was applied to 103 patients, and the degree of acetabular migration was determined from radiograph images of 91 AR procedures, of which 40 were segmental/combined and 51 were cavitary reconstructions. RESULTS: The frequency of aseptic acetabular loosening was 3% while that of thromboembolic events was 4.1%. According to Harris Hip Score, 87.4% of outcomes were classified as excellent/good after an average follow-up period of 6.4 years irrespective of the type of acetabular defect. Horizontal and/or vertical acetabular migrations and changes in angular tilt were observed in all ARs, although the minor movements detected did not undermine the structural stability of the reconstructions or the functional capacity of patients. CONCLUSION: The described THA/AR technique can be used effectively in the reconstruction of segmental/combined and cavitary acetabular defects. The success of the technique as applied to segmental/combined defects was attributed in part to the rigorous rehabilitation protocol with temporary postoperative weight-bearing restriction.

Circulation of Nor98 Atypical Scrapie in Portuguese Sheep Confirmed by Transmission of Isolates into Transgenic Ovine ARQ-PrP Mice.

Portugal was among the first European countries to report cases of Atypical Scrapie (ASc), the dominant form of Transmissible Spongiform Encephalopathy (TSE) in Portuguese small ruminants. Although the diagnostic phenotypes observed in Portuguese ASc cases seem identical to those described for Nor98, unequivocal identification requires TSE strain-typing using murine bioassays. In this regard, we initiated characterization of ASc isolates from sheep either homozygous for the ARQ genotype or the classical scrapie-resistant ARR genotype. Isolates from such genotypes were transmitted to TgshpXI mice expressing ovine PrPARQ. Mean incubation periods were 414 ± 58 and 483 ± 107 days in mice inoculated with AL141RQ/AF141RQ and AL141RR/AL141RR sheep isolates, respectively. Both isolates produced lesion profiles similar to French ASc Nor98 'discordant cases', where vacuolation was observed in the hippocampus (G6), cerebral cortex at the thalamus (G8) level, cerebellar white matter (W1) and cerebral peduncles (W3). Immunohistochemical PrPSc deposition was observed in the hippocampus, cerebellar cortex, cerebellar white matter and cerebral peduncles in the form of aggregates and fine granules. These findings were consistent with previously reported cases of ASc Nor98 transmitted to transgenic TgshpXI mice, confirming that the ASc strain present in Portuguese sheep corresponds to ASc Nor98.

Preclinical Therapy with Vitamin D3 in Experimental Encephalomyelitis: Efficacy and Comparison with Paricalcitol.

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS). MS and its animal model called experimental autoimmune encephalomyelitis (EAE) immunopathogenesis involve a plethora of immune cells whose activation releases a variety of proinflammatory mediators and free radicals. Vitamin D3 (VitD) is endowed with immunomodulatory and antioxidant properties that we demonstrated to control EAE development. However, this protective effect triggered hypercalcemia. As such, we compared the therapeutic potential of VitD and paricalcitol (Pari), which is a non-hypercalcemic vitamin D analog, to control EAE. From the seventh day on after EAE induction, mice were injected with VitD or Pari every other day. VitD, but not Pari, displayed downmodulatory ability being able to reduce the recruitment of inflammatory cells, the mRNA expression of inflammatory parameters, and demyelination at the CNS. Lower production of proinflammatory cytokines by lymph node-derived cells and IL-17 by gut explants, and reduced intestinal inflammation were detected in the EAE/VitD group compared to the EAE untreated or Pari groups. Dendritic cells (DCs) differentiated in the presence of VitD developed a more tolerogenic phenotype than in the presence of Pari. These findings suggest that VitD, but not Pari, has the potential to be used as a preventive therapy to control MS severity.

Concordance among in vivo reflectance confocal microscopy, trichoscopy, and histopathology in the evaluation of scalp discoid lupus.

BACKGROUND: Reflectance confocal microscopy (RCM) has been used for the evaluation of several inflammatory skin conditions, including skin discoid lupus erythematosus (DLE), and has been correlated with conventional histopathology (HP). However, RCM is not being widely used in trichology. Few reports and just preliminary data suggest the use of RCM as a complementary tool in alopecias. OBJECTIVES: To correlate the major RCM features of scalp DLE with trichoscopy and HP findings of biopsy specimens obtained from the same lesions. METHODS: This is an observational, analytical, and cross-sectional study involving 12 patients with a clinically established diagnosis of scalp DLE. Patients underwent global clinical photograph, trichoscopy, and RCM examination in the same site followed by two 4-mm punch biopsy specimens for HP analysis. Inter-methods agreement among RCM imaging, trichoscopy, and horizontal histopathology sections (HHS) were calculated using Cohen Kappa (k) statistics. RESULTS: Statistical analysis of the agreement between RCM and HP features disclosed an overall agreement similar to skin DLE. Seven of the eleven features evaluated had agreement superior to 75%. We also evaluated RCM features associated with three of their corresponding trichoscopic findings for further investigation of their agreement with HP. Statistical analysis showed an enhancement with agreement of 86% when the non-invasive techniques are used together. CONCLUSION: Consistent correlation between RCM and HP observed in our study supports the reliability of RCM in the diagnosis of scalp DLE. RCM may be considered a promising tool for scalp DLE microscopic evaluation and presents similar RCM features to DLE in other body sites. By associating clinical, trichoscopic and RCM evaluation, dermatologists will have a non-invasive arsenal for the assessment of hair and scalp disorders, benefiting patients.

Sustainable Galactarate-Based Polymers: Multi-Enzymatic Production of Pectin-Derived Polyesters.

Large amounts of agricultural wastes are rich in pectins that, in many cases, disrupt the processing of food residues due to gelation. Despite pectins being a promising sustainable feedstock for bio-based chemical production, the current pathways to produce platform molecules from this polysaccharide are hazardous and entail the use of strong acids. The present work describes a sequence of biocatalyzed reactions that involves 1) the extraction of pectin from sugar beet pulp and enzymatic recovery of galacturonic acid (GalA), followed by 2) the enzymatic oxidation of the GalA aldehyde and the recovery of galactaric acid (GA), and 3) the biocatalyzed polycondensation of GA to obtain fully bio-based polyesters carrying lateral hydroxy functionalities. The acid-free pectin extraction is optimized using enzymes and microwave technology. The conditions for enzymatic oxidation of GalA allow the separation of the GA produced by a simple centrifugation step that leads to the enzyme-catalyzed polycondensation reactions.

Vitamin D supplementation alters the expression of genes associated with hypertension and did not induce DNA damage in rats.

Vitamin D3 deficiency has been correlated with altered expression of genes associated with increased blood pressure (BP); however, the role of vitamin D3 supplementation in the genetic mechanisms underlying hypertension remains unclear. Thus, the aim of this study was investigate the consequences of vitamin D3 supplemented (10,000 IU/kg) or deficient (0 IU/kg) diets on regulation of expression of genes related to hypertension pathways in heart cells of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) controls. An additional aim was to assess the impact of vitamin D3 on DNA damage and oxidative stress markers. The gene expression profiles were determined by PCR array, DNA damage was assessed by an alkaline comet assay, and oxidative stress markers by measurement of thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) levels. In SHR rats data showed that the groups of genes most differentially affected by supplemented and deficient diets were involved in BP regulation and renin-angiotensin system. In normotensive WKY controls, the profile of gene expression was similar between the two diets. SHR rats were more sensitive to changes in gene expression induced by dietary vitamin D3 than normotensive WKY animals. In addition to gene expression profile, vitamin D3 supplemented diet did not markedly affect DNA or levels of TBARS and GSH levels in both experimental groups. Vitamin D3 deficient diet produced lipid peroxidation in SHR rats. The results of this study contribute to a better understanding of the role of vitamin D3 in the genetic mechanisms underlying hypertension. Abbreviations: AIN, American Institute of Nutrition; EDTA, disodium ethylenediaminetetraacetic acid; GSH, glutathione; PBS, phosphate buffer solution; SHR, spontaneously hypertensive rats; TBARS, thiobarbituric acid reactive substances; WKY, Wistar Kyoto.