GestaltMatcher Database - A global reference for facial phenotypic variability in rare human diseases.

The most important factor that complicates the work of dysmorphologists is the significant phenotypic variability of the human face. Next-Generation Phenotyping (NGP) tools that assist clinicians with recognizing characteristic syndromic patterns are particularly challenged when confronted with patients from populations different from their training data. To that end, we systematically analyzed the impact of genetic ancestry on facial dysmorphism. For that purpose, we established the GestaltMatcher Database (GMDB) as a reference dataset for medical images of patients with rare genetic disorders from around the world. We collected 10,980 frontal facial images - more than a quarter previously unpublished - from 8,346 patients, representing 581 rare disorders. Although the predominant ancestry is still European (67%), data from underrepresented populations have been increased considerably via global collaborations (19% Asian and 7% African). This includes previously unpublished reports for more than 40% of the African patients. The NGP analysis on this diverse dataset revealed characteristic performance differences depending on the composition of training and test sets corresponding to genetic relatedness. For clinical use of NGP, incorporating non-European patients resulted in a profound enhancement of GestaltMatcher performance. The top-5 accuracy rate increased by +11.29%. Importantly, this improvement in delineating the correct disorder from a facial portrait was achieved without decreasing the performance on European patients. By design, GMDB complies with the FAIR principles by rendering the curated medical data findable, accessible, interoperable, and reusable. This means GMDB can also serve as data for training and benchmarking. In summary, our study on facial dysmorphism on a global sample revealed a considerable cross ancestral phenotypic variability confounding NGP that should be counteracted by international efforts for increasing data diversity. GMDB will serve as a vital reference database for clinicians and a transparent training set for advancing NGP technology.

GestaltMatcher Database - A global reference for the facial phenotypic variability of rare human diseases.

Dysmorphologists sometimes encounter challenges in recognizing disorders due to phenotypic variability influenced by factors such as age and ethnicity. Moreover, the performance of Next Generation Phenotyping Tools such as GestaltMatcher is dependent on the diversity of the training set. Therefore, we developed GestaltMatcher Database (GMDB) - a global reference for the phenotypic variability of rare diseases that complies with the FAIR-principles. We curated dysmorphic patient images and metadata from 2,224 publications, transforming GMDB into an online dynamic case report journal. To encourage clinicians worldwide to contribute, each case can receive a Digital Object Identifier (DOI), making it a citable micro-publication. This resulted in a collection of 2,312 unpublished images, partly with longitudinal data. We have compiled a collection of 10,189 frontal images from 7,695 patients representing 683 disorders. The web interface enables gene- and phenotype-centered queries for registered users (https://db.gestaltmatcher.org/). Despite the predominant European ancestry of most patients (59%), our global collaborations have facilitated the inclusion of data from frequently underrepresented ethnicities, with 17% Asian, 4% African, and 6% with other ethnic backgrounds. The analysis has revealed a significant enhancement in GestaltMatcher performance across all ethnic groups, incorporating non-European ethnicities, showcasing a remarkable increase in Top-1-Accuracy by 31.56% and Top-5-Accuracy by 12.64%. Importantly, this improvement was achieved without altering the performance metrics for European patients. GMDB addresses dysmorphology challenges by representing phenotypic variability and including underrepresented groups, enhancing global diagnostic rates and serving as a vital clinician reference database.

Revisiting the Basic Cycle: Prospects by Undergraduates' Students of a Brazilian Dentistry School

Objective: To analyze the perception of undergraduates' students in a Dentistry School about the impact of basic disciplines on their professional development, as well the integration of this knowledge with the professional sphere. Material and Methods: It is a qualitative research study carried out through focus groups comprised of dentistry students close to finishing their degree. The data were analyzed by the thematic content analysis. Results: Four categories derived from the empirical material: "Disassociation of basic disciplines within the professional cycle", "Autonomy or transference of responsibility", "Campus-DOD distancing" and "Humanization of health care from first moments". The narratives showed the difficulties faced in order to effect, indeed, integration between the basic cycle and the curricular components of the vocational cycle. It was also evident the decontextualization of the basic cycle with the perspective of approach with professional practice. In addition, student's protagonist posture and learning how to humanize health care were identified as important factors to be debated and improved in the curriculum from the beginning of the course. Conclusion: The difficulties faced in order to effect an actual integration between the basic disciplines and the professional disciplines bring undesirable consequences upon undergraduate, being fundamental that the construction of new pedagogical projects means an effective integration of the contents to the curriculum design, avoiding any fragmentation between the basic and vocational cycle.

Rethinking the concept of sepsis and septic shock.

Sepsis is a major global health problem and represents a challenge for physicians all over the world. The knowledge of sepsis and septic shock is a topic of interest among the scientific community and society in general. New guidelines for management of sepsis and septic shock were developed in 2016, providing an update on this area. In Sepsis-3 new definitions for sepsis and septic shock were published. The purpose of this narrative review is to discuss and compare the new criteria of 2016 with the old criteria, purposing at the same time an alternative approach for this topic. SOFA criteria (Sequential Organ Failure Assessment Score) are more complete, but too extensive and usually difficult to apply outside the intensive care units, therefore inducing potentially delay in the proper treatment. We purpose combined criteria for the selection of sepsis patients. Initially, we could apply qSOFA (quick Sepsis Related Organ Failure Assessment) criteria, due to its easy application, associated with the SIRS (systemic inflammatory response syndrome) criteria, allowing to select the patients who are infected and need faster treatment. In that way we would use the best of old and newest criteria, allowing the early selection of patients who are infected and require faster treatment, while the search for a better and faster tool continues.

The role of palliative care in addressing the health needs of Syrian refugees in Jordan.

Refugees are often afflicted with health conditions that require long-term, specialized and continuous care services that are costly and difficult to secure in host countries and camp settings. This study interviewed 21 Syrian refugees in Jordan with life-limiting conditions such as cancer, diabetes, chronic disability and renal failure, and 4 caregivers caring for refugee children with similar conditions. This study found that patients in refugee camps and communities would benefit from receiving palliative care services that are often either unavailable or inaccessible. Training humanitarian teams and primary care providers to implement pain management, offer psychosocial support services and address emotional, spiritual, and psychological conditions could ameliorate many of the problems faced by this vulnerable group.

Procalcitonin as Biomarker of Infection: Implications for Evaluation and Treatment.

Procalcitonin (PCT) is a quickly measurable marker, assumed to have high sensitivity and specificity for sepsis and infection. A literature search was conducted to evaluate PCT ability as a diagnostic and prognostic tool in infectious processes and its ability to monitor the antibiotic therapy. PCT level is increased in bacterial and fungal infections, but not in viral infections, with a significantly higher level in patients with bacteremia compared with uninfected patients (2.5 vs. 0.3 ng/mL; P < 0.0001). A PCT value of ≤0.1 ng/mL discards bacteremia and microbiological tests (negative predictive value of 96.3%), >0.1 ng/mL needs microbiological tests, and >1.0 ng/mL is indicative of bacteremia. Antibiotic treatment algorithms guided by PCT decreased the need for antibiotic treatment in approximately 50%. PCT is a promising test in clinical practice to decide the introduction of antibiotic therapy in addition to the existing tools, without neglecting the clinical assessment, with a significant decrease in costs.

Clenbuterol storage stability in the bovine urine and liver samples used for European official control in the azores islands (portugal).

Clenbuterol is a well-known growth promoter, illegally used in farm animals, especially in cattle. Samples collected for the screening of beta(2)-agonist residues in Portuguese Azores Islands must travel through all the nine islands until they reach Azores Central Laboratory. If any suspicious sample is detected, it must be further transported to the National Reference Laboratory in Lisbon for confirmation. As a consequence of these circumstances, samples are submitted to different transport and storage times, as well as different temperature conditions and in some cases successive freezing and thawing cycles. As clenbuterol is the most detected beta(2)-agonist growth promoter in the Portuguese Residue Monitoring Plan, studies were conducted on the stability of this compound in incurred samples (bovine liver and urine) at +4, -20 and -60 degrees C over time. Samples kept at -20 degrees C were also analyzed over time after successive freezing and thawing cycles. The analyses of clenbuterol over time were performed by gas chromatography-mass spectrometry (GC-MS) with selected ion monitoring (SIM). Clenbuterol in incurred urine and liver samples was significantly stable up to 20 weeks at -20 and -60 degrees C and after, at least, six consecutive freezings and thawings. At +4 degrees C, clenbuterol remained stable, at least until 12 weeks in urine and up to 20 weeks in liver.