Effect of an Albumin Infusion Treatment Protocol on Delayed Cerebral Ischemia and Relevant Outcomes in Patients with Subarachnoid Hemorrhage.

BACKGROUND: An institutional management protocol for patients with subarachnoid hemorrhage (SAH) based on initial cardiac assessment, permissiveness of negative fluid balances, and use of a continuous albumin infusion as the main fluid therapy for the first 5 days of the intensive care unit (ICU) stay was implemented at our hospital in 2014. It aimed at achieving and maintaining euvolemia and hemodynamic stability to prevent ischemic events and complications in the ICU by reducing periods of hypovolemia or hemodynamic instability. This study aimed at assessing the effect of the implemented management protocol on the incidence of delayed cerebral ischemia (DCI), mortality, and other relevant outcomes in patients with SAH during ICU stay. METHODS: We conducted a quasi-experimental study with historical controls based on electronic medical records of adults with SAH admitted to the ICU at a tertiary care university hospital in Cali, Colombia. The patients treated between 2011 and 2014 were the control group, and those treated between 2014 and 2018 were the intervention group. We collected baseline clinical characteristics, cointerventions, occurrence of DCI, vital status after 6 months, neurological status after 6 months, hydroelectrolytic imbalances, and other SAH complication. Multivariable and sensitivity analyses that controlled for confounding and considered the presence of competing risks were used to adequately estimate the effects of the management protocol. The study was approved by our institutional ethics review board before study start. RESULTS: One hundred eighty-nine patients were included for analysis. The management protocol was associated with a reduced incidence of DCI (hazard ratio 0.52 [95% confidence interval 0.33-0.83] from multivariable subdistribution hazards model) and hyponatremia (relative risk 0.55 [95% confidence interval 0.37-0.80]). The management protocol was not associated with higher hospital or long-term mortality, nor with a higher occurrence of other unfavorable outcomes (pulmonary edema, rebleeding, hydrocephalus, hypernatremia, pneumonia). The intervention group also had lower daily and cumulative administered fluids compared with historic controls (p < 0.0001). CONCLUSIONS: A management protocol based on hemodynamically oriented fluid therapy in combination with a continuous albumin infusion as the main fluid during the first 5 days of the ICU stay appears beneficial for patients with SAH because it was associated with reduced incidence of DCI and hyponatremia. Proposed mechanisms include improved hemodynamic stability that allows euvolemia and reduces the risk of ischemia, among others.

Genomic relationships of the polyploid rhizoma peanut (Arachis glabrata Benth.) inferred by genomic in situ hybridization (GISH).

The rhizoma peanut (Arachis glabrata Benth., section Rhizomatosae) is a tetraploid perennial legume. Although several A. glabrata cultivars have been developed as forage and ornamental turf, the origin and genomic constitution of this species are still unknown. In this study, we evaluated the affinity between the genomes of A. glabrata and the probable diploid donors of the sections Rhizomatosae, Arachis, Erectoides and Procumbentes by genomic in situ hybridization (GISH). Single GISH analyses detected that species of the sections Erectoides (E2 subgenome) and Procumbentes (E3 subgenome) were the diploid species with the highest degree of genomic affinity with A. glabrata. Based on single GISH experiments and DNA sequence similarity, three species -A. duranensis, A. paraguariensis subsp. capibarensis, and A. rigonii-, which showed the most uniform and brightest hybridization patterns and lowest genetic distance, were selected as probes for double GISH experiments. Double GISH experiments showed that A. glabrata is constituted by four identical or very similar chromosome complements. In these assays, A. paraguariensis subsp. capibarensis showed the highest brightness onto A. glabrata chromosomes. Thus, our results support the autopolyploid origin of A. glabrata and show that the species with E2 subgenome are the most probable ancestors of this polyploid legume forage.

Comparative repeatome analysis reveals new evidence on genome evolution in wild diploid Arachis (Fabaceae) species.

MAIN CONCLUSION: Opposing changes in the abundance of satellite DNA and long terminal repeat (LTR) retroelements are the main contributors to the variation in genome size and heterochromatin amount in Arachis diploids. The South American genus Arachis (Fabaceae) comprises 83 species organized in nine taxonomic sections. Among them, section Arachis is characterized by species with a wide genome and karyotype diversity. Such diversity is determined mainly by the amount and composition of repetitive DNA. Here we performed computational analysis on low coverage genome sequencing to infer the dynamics of changes in major repeat families that led to the differentiation of genomes in diploid species (x = 10) of genus Arachis, focusing on section Arachis. Estimated repeat content ranged from 62.50 to 71.68% of the genomes. Species with different genome composition tended to have different landscapes of repeated sequences. Athila family retrotransposons were the most abundant and variable lineage among Arachis repeatomes, with peaks of transpositional activity inferred at different times in the evolution of the species. Satellite DNAs (satDNAs) were less abundant, but differentially represented among species. High rates of evolution of an AT-rich superfamily of satDNAs led to the differential accumulation of heterochromatin in Arachis genomes. The relationship between genome size variation and the repetitive content is complex. However, largest genomes presented a higher accumulation of LTR elements and lower contents of satDNAs. In contrast, species with lowest genome sizes tended to accumulate satDNAs in detriment of LTR elements. Phylogenetic analysis based on repetitive DNA supported the genome arrangement of section Arachis. Altogether, our results provide the most comprehensive picture on the repeatome dynamics that led to the genome differentiation of Arachis species.

New Middle Miocene Ape (Primates: Hylobatidae) from Ramnagar, India fills major gaps in the hominoid fossil record.

The fossil record of 'lesser apes' (i.e. hylobatids = gibbons and siamangs) is virtually non-existent before the latest Miocene of East Asia. However, molecular data strongly and consistently suggest that hylobatids should be present by approximately 20 Ma; thus, there are large temporal, geographical, and morphological gaps between early fossil apes in Africa and the earliest fossil hylobatids in China. Here, we describe a new approximately 12.5-13.8 Ma fossil ape from the Lower Siwaliks of Ramnagar, India, that fills in these long-standing gaps with implications for hylobatid origins. This ape represents the first new hominoid species discovered at Ramnagar in nearly a century, the first new Siwalik ape taxon in more than 30 years, and likely extends the hylobatid fossil record by approximately 5 Myr, providing a minimum age for hylobatid dispersal coeval to that of great apes. The presence of crown hylobatid molar features in the new species indicates an adaptive shift to a more frugivorous diet during the Middle Miocene, consistent with other proposed adaptations to frugivory (e.g. uricase gene silencing) during this time period as well.

Enamel thickness variation in the deciduous dentition of extant large-bodied hominoids.

OBJECTIVES: Enamel thickness features prominently in hominoid evolutionary studies. To date, however, studies of enamel thickness in humans, great apes, and their fossil relatives have focused on the permanent molar row. Comparatively little research effort has been devoted to tissue proportions within deciduous teeth. Here we attempt to fill this gap by documenting enamel thickness variation in the deciduous dentition of extant large-bodied hominoids. MATERIALS AND METHODS: We used microcomputed tomography to image dental tissues in 80 maxillary and 78 mandibular deciduous premolars of Homo sapiens, Pan troglodytes, Gorilla, and Pongo. Two-dimensional virtual sections were created from the image volumes to quantify average (AET) and relative (RET) enamel thickness, as well as its distribution across the crown. RESULTS: Our results reveal no significant differences in enamel thickness among the great apes. Unlike the pattern present in permanent molars, Pongo does not stand out as having relatively thicker-enameled deciduous premolars than P. troglodytes and Gorilla. Humans, on the other hand, possess significantly thicker deciduous premolar enamel in comparison to great apes. Following expectations from masticatory biomechanics, we also find that the "functional" side (protocone, protoconid) of deciduous premolars generally possesses thicker enamel than the "nonfunctional" side. DISCUSSION: Our study lends empirical support to anecdotal observations that patterns of AET and RET observed for permanent molars of large-bodied apes do not apply to deciduous premolars. By documenting enamel thickness variation in hominoid deciduous teeth, this study provides the comparative context to interpret rates and patterns of wear of deciduous teeth and their utility in life history reconstructions.

Chromosome diversity in species of the genus Arachis, revealed by FISH and CMA/DAPI banding, and inferences about their karyotype differentiation.

The species of the genus Arachis (Leguminosae) are ordered into nine sections. The assignment of genome types in this genus has been based on cross-compatibility analysis and molecular cytogenetic studies. The latter has also allowed karyotypically establishing well-defined genomes and reassigning the genome of several species. However, most of these studies have been focused mainly on the sections Arachis and Rhizomatosae. To increase the knowledge about the chromosome diversity of the whole genus, here we performed a detailed karyotype characterization of representative species of most of the sections and genomes of Arachis. This characterization included chromosome morphology, CMA/DAPI chromosome banding, and chromosome marker localization (rDNAloci and one satDNA sequence) by fluorescent in situ hybridization (FISH). Based on the data obtained and other previously published data, we established the karyotype similarities by cluster analysis and defined eleven karyotype groups. The grouping was partly coincident with the traditional genome assignment, except for some groups and some individual species. Karyotype similarities among some genomes were also found. The main characteristics of each karyotype group of Arachis were summarized. Together, our results provide information that may be beneficial for future cytogenetic and evolutionary studies, and also contribute to the identification of interspecific hybrids.

A distinguishing feature of Pongo upper molars and its implications for the taxonomic identification of isolated hominid teeth from the Pleistocene of Asia.

OBJECTIVES: The taxonomic status of isolated hominoid teeth from the Asian Pleistocene has long been controversial due to difficulties distinguishing between pongine and hominin molars given their high degree of morphometrical variation and overlap. Here, we combine nonmetric and geometric morphometric data to document a dental pattern that appears to be taxonomically diagnostic among Pongo. We focus on the protoconule, a cuspule of well-documented evolutionary history, as well as on shape differences of the mesial fovea of the upper molars. MATERIALS AND METHODS: We examined 469 upper molars of eight hominid genera (Australopithecus, Paranthropus, Homo, Meganthropus, Sivapithecus, Pan, Gorilla, and Pongo), including representatives of Homo erectus and extinct and recent Pongo. Analyses were conducted at the enamel-dentine junction to overcome the limitations introduced by dental wear. RESULTS: We found that a moderate or large protoconule is present in ~80% of Pleistocene and extant Pongo. Conversely, a moderate to pronounced protoconule in hominins, Meganthropus, and African great apes occurs in low frequencies (~0-20%). Canonical variate analyses for the mesial fovea show that Pleistocene and extant Pongo cluster together and are clearly differentiated from all other groups, except for Sivapithecus. DISCUSSION: This study suggests that the protoconule and the shape of the mesial fovea in upper molars are useful features for the taxonomic identification of isolated hominid teeth. By identifying these new features, our results can contribute to the better understanding of hominoid evolutionary history and biogeography during the Asian Pleistocene. However, we emphasize that the reported features should be used in combination with other diagnostic variables for the most accurate taxonomic assessments.

Homology, homoplasy and cusp variability at the enamel-dentine junction of hominoid molars.

Evolutionary studies of mammalian teeth have generally concentrated on the adaptive and functional significance of dental features, whereas the role of development on phenotypic generation and as a source of variation has received comparatively little attention. The present study combines an evolutionary biological framework with state-of-the-art imaging techniques to examine the developmental basis of variation of accessory cusps. Scholars have long used the position and relatedness of cusps to other crown structures as a criterion for differentiating between developmentally homologous and homoplastic features, which can be evaluated with greater accuracy at the enamel-dentine junction (EDJ). Following this approach, we collected digital models of the EDJ and outer enamel surface of more than 1000 hominoid teeth to examine whether cusp 5 of the upper molars (UM C5) and cusps 6 and 7 of the lower molars (LM C6 and LM C7) were associated each with a common developmental origin across species. Results revealed that each of these cusps can develop in a variety of ways, in association with different dental tissues (i.e. oral epithelium, enamel matrix) and dental structures (i.e. from different cusps, crests and cingula). Both within and between species variability in cusp origin was highest in UM C5, followed by LM C7, and finally LM C6. The lack of any species-specific patterns suggests that accessory cusps in hominoids are developmentally homoplastic and that they may not be useful for identifying phylogenetic homology. An important and unanticipated finding of this study was the identification of a new taxonomically informative feature at the EDJ of the upper molars, namely the post-paracone tubercle (PPT). We found that the PPT was nearly ubiquitous in H. neanderthalensis and the small sample of Middle Pleistocene African and European humans (MPAE) examined, differing significantly from the low frequencies observed in all other hominoids, including Pleistocene and recent H. sapiens. We emphasize the utility of the EDJ for human evolutionary studies and demonstrate how features that look similar at the external surface may be the product of different developmental patterns. This study also highlights the importance of incorporating both developmental and morphological data into evolutionary studies in order to gain a better understanding of the evolutionary significance of dental and skeletal features.

Cytogenetic evidences on the evolutionary relationships between the tetraploids of the section Rhizomatosae and related diploid species (Arachis, Leguminosae).

Rhizomatosae is a taxonomic section of the South American genus Arachis, whose diagnostic character is the presence of rhizomes in all its species. This section is of particular evolutionary interest because it has three polyploid (A. pseudovillosa, A. nitida and A. glabrata, 2n = 4x = 40) and only one diploid (A. burkartii, 2n = 2x = 20) species. The phylogenetic relationships of these species as well as the polyploidy nature and the origin of the tetraploids are still controversial. The present study provides an exhaustive analysis of the karyotypes of all rhizomatous species and six closely related diploid species of the sections Erectoides and Procumbentes by cytogenetic mapping of DAPI/CMA heterochromatin bands and 5S and 18-26S rDNA loci. Chromosome banding showed variation in the DAPI heterochromatin distribution pattern, which, together with the number and distribution of rDNA loci, allowed the characterization of all species studied here. The bulk of chromosomal markers suggest that the three rhizomatous tetraploid species constitute a natural group and may have at least one common diploid ancestor. The cytogenetic data of the diploid species analyzed evidenced that the only rhizomatous diploid species-A. burkartii-has a karyotype pattern different from those of the rhizomatous tetraploids, showing that it is not likely the genome donor of the tetraploids and the non-monophyletic nature of the section Rhizomatosae. Thus, the tetraploid species should be excluded from the R genome, which should remain exclusively for A. burkartii. Instead, the karyotype features of these tetraploids are compatible with those of different species of the sections Erectoides and Procumbentes (E genome species), suggesting the hypothesis of multiple origins of these tetraploids. In addition, the polyploid nature and the group of diploid species closer to the tetraploids are discussed.

Description of a new species of Hoolock gibbon (Primates: Hylobatidae) based on integrative taxonomy.

We describe a species of Hoolock gibbon (Primates: Hylobatidae) that is new to science from eastern Myanmar and southwestern China. The genus of hoolock gibbons comprises two previously described living species, the western (Hoolock hoolock) and eastern hoolock (H. leuconedys) gibbons, geographically isolated by the Chindwin River. We assessed the morphological and genetic characteristics of wild animals and museum specimens, and conducted multi-disciplinary analyses using mitochondrial genomic sequences, external morphology, and craniodental characters to evaluate the taxonomic status of the hoolock population in China. The results suggest that hoolocks distributed to the east of the Irrawaddy-Nmai Hka Rivers, which were previously assigned to H. leuconedys, are morphologically and genetically distinct from those to the west of the river, and should be recognized as a new species, the Gaoligong hoolock gibbon or skywalker hoolock gibbon (H. tianxing sp. nov.). We consider that the new species should be categorized as Endangered under IUCN criteria. The discovery of the new species focuses attention on the need for improved conservation of small apes, many of which are in danger of extinction in southern China and Southeast Asia.

[Primary hyperparathyroidism in pregnancy: a case report and bibliographical review]. / Hiperparatiroidismo primario en el embarazo: reporte de un caso y revisión de la bibliografía.

Primary hyperparathyroidism in pregnant women is an uncommon disease. It could be easily misdiagnosed because physiologic changes during pregnancy; in some cases, patients could remain asymptomatic maintaining elevated calcium serum levels, and this situation represents a threat to the health of both mother and fetus. Maternal complications of primary hyperparathyroidism include nepfhrolithiasis, pancreatitis, cardiac arrhythmias, hypertension, nausea and vomiting. Most commonly, the underlying aetiology is a solitary parathyroid adenoma whereby parathyroidectomy is the only cure. We present the case of a 21-year old patient, with primary hyperparathyroidism diagnosed in the third trimester of pregnancy, complicated with pancreatitis and gestational hypertension. We performed a caesarean section due to elevated calcium levels. Post-caesarean section, she was referred to a third level institute (National Institute of Cancerology of Mexico), were she undergone parathyroidectomy, with benign histopathological results. An appropriate medical/surgical management of hyperparathyroidism during pregnancy is necessary for avoiding maternal and fetal complications.

A Contextualization of Transgender Women and Condom Use Using the HIV Syndemic Framework: Scoping Review.

Objective: To contextualize condom use in the transgender women population utilizing the HIV syndemic framework. Methods: Studies reporting condom use frequency and syndemic factors associated with HIV risk in transgender women were systematically searched. We followed the Scoping Reviews (PRISMA-ScR) checklist. Results: Social factors have a proven relationship with using condoms and HIV among transgender women. Syndemic factors, defined as co-occurring adverse factors that interact to contribute to risk behaviors, deserve a specific analysis to develop strategies to face HIV among transgender women. Conclusions: A syndemic perspective allows to generate specific health intervention and prevention policies to protect transgender women.

[Ectopic intraligamentary pregnancy]. / Embarazo ectópico intraligamentario.

Intraligamentary pregnancy is a rare form of ectopic pregnancy and a type of abdominal pregnancy, preoperative diagnosis is very difficult. This paper describes the case of a 24-year-old woman with a history of uterine curettage uncomplicated; she consulted due to abdomina pain in the right lower quadrant of seven days of duration, which gradually increased in intensity being 10/10 visual scale analogous (VAS). Obstetrical ultrasound was performed reporting: ectopic localization to annex right of 15.2 weeks gestational age, with heart rate of 152 beats per minute. The patient was admitted and underwent to emergency exploratory laparotomy, which found right paratubaric ectopic pregnancy. The histopathology report was of broad ligament ectopic pregnancy. Specimen of 9 x 8 x 7.5 cm and 200 grams.

Adherence to Oral Pre-Exposure Prophylaxis Intervention by Transgender Women: A Systematic Review.

Prevalence of human immunodeficiency virus (HIV) is higher in transgender populations. Pre-exposure prophylaxis (PrEP) intervention is successful in reducing HIV acquisition. We aimed to investigate the adherence to oral PrEP by HIV-negative transgender women (TW). We followed the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA Statement. We searched in WoS, OVID, Scopus, MEDLINE, and the Cochrane Central Register of Controlled Trials databases. Participation and adherence to the intervention were low for TW compared to cisgender men who have sex with men (cMSM), and it was measured mostly by self-report (72.7%) or tenofovir-diphosphate/emtricitabine triphosphate dried blood spot (45.5%). Awareness should increase and the effect of oral PrEP on gender-affirming hormone therapy should be explained to TW at the beginning of the trials. One limitation is that our sample size was dominated by two Thai studies with TW sex workers. Future studies should evaluate adherence to new PrEP modalities.

NKG2D-CAR memory T cells target pediatric T-cell acute lymphoblastic leukemia in vitro and in vivo but fail to eliminate leukemia initiating cells.

Introduction: Refractory/relapsed pediatric acute leukemia are still clinically challenging and new therapeutic strategies are needed. Interactions between Natural Killer Group 2D (NKG2D) receptor, expressed in cytotoxic immune cells, and its ligands (NKG2DL), which are upregulated in leukemic blasts, are important for anti-leukemia immunosurveillance. Nevertheless, leukemia cells may develop immunoescape strategies as NKG2DL shedding and/or downregulation. Methods: In this report, we analyzed the anti-leukemia activity of NKG2D chimeric antigen receptor (CAR) redirected memory (CD45RA-) T cells in vitro and in a murine model of T-cell acute lymphoblastic leukemia (T-ALL). We also explored in vitro how soluble NKG2DL (sNKG2DL) affected NKG2D-CAR T cells' cytotoxicity and the impact of NKG2D-CAR T cells on Jurkat cells gene expression and in vivo functionality. Results: In vitro, we found NKG2D-CAR T cells targeted leukemia cells and showed resistance to the immunosuppressive effects exerted by sNKG2DL. In vivo, NKG2D-CAR T cells controlled T cell leukemia burden and increased survival of the treated mice but failed to cure the animals. After CAR T cell treatment, Jurkat cells upregulated genes related to proliferation, survival and stemness, and in vivo, they exhibited functional properties of leukemia initiating cells. Discussion: The data here presented suggest, that, in combination with other therapeutic approaches, NKG2D-CAR T cells could be a novel treatment for pediatric T-ALL.

Carabelli's trait revisited: an examination of mesiolingual features at the enamel-dentine junction and enamel surface of Pan and Homo sapiens upper molars.

Carabelli's trait is a morphological feature that frequently occurs on the mesiolingual aspect of Homo sapiens upper molars. Similar structures also referred to as Carabelli's trait have been reported in apes and fossil hominins. However, the morphological development and homology of these mesiolingual structures among hominoids are poorly understood. In this study, we employ micro-computed tomography to image the enamel-dentine junction (EDJ) and outer enamel surface (OES) of Pan (n = 48) and H. sapiens (n = 52) upper molars. We investigate the developmental origin of mesiolingual features in these taxa and establish the relative contribution of the EDJ and enamel cap to feature expression. Results demonstrate that mesiolingual features of H. sapiens molars develop at the EDJ and are similarly expressed at the OES. Morphological variation at both surfaces in this taxon can satisfactorily be assessed using standards for Carabelli's trait developed by the Arizona State University Dental Anthropology System (ASUDAS). Relative to H. sapiens, Pan has an even greater degree of correspondence in feature expression between the EDJ and OES. Morphological manifestations in Pan molars are not necessarily limited to the protocone and are best characterized by a lingual cingulum that cannot be captured by the ASUDAS. Cusp-like structures, similar to those seen in marked Carabelli's trait expressions in H. sapiens, were not found in Pan. This study provides a foundation for further analyses on the evolutionary history of mesiolingual dental traits within the hominoid lineage. It also highlights the wealth of morphological data that can be obtained at the EDJ for understanding tooth development and for characterizing tooth crown variation in worn fossil teeth.

Integrated Quantitative Neuro-Transcriptome Analysis of Several Brain Areas in Human Trisomy 21.

BACKGROUND: Although Down syndrome (DS) is the most frequent human chromosomal disorder and it causes mainly intellectual disability, its clinical presentation is complex and variable. OBJECTIVE: We aimed to analyze and compare the transcriptome disruption in several brain areas from individuals with DS and euploid controls as a new approach to consider a global systemic differential disruption of gene expression beyond chromosome 21. METHODS: We used data from a DNA microarray experiment with ID GSE59630 previously deposited in the GEO DataSet of NCBI database. The array contained log2 values of 17,537 human genes expressed in several aeras of the human brain. We calculated the differential gene expression (Z-ratio) of all genes. RESULTS: We found several differences in gene expression along the DS brain transcriptome, not only in the genes located at chromosome 21 but in other chromosomes. Moreover, we registered the lowest Z-ratio correlation between the age ranks of 16-22 weeks of gestation and 39-42 years (R2 = 0.06) and the highest Z-ratio correlation between the age ranks of 30-39 years and 40-42 years (R2 = 0.89). The analysis per brain areas showed that the hippocampus and the cerebellar cortex had the most different gene expression pattern when compared to the brain as a whole. CONCLUSIONS: Our results support the hypothesis of a systemic imbalance of brain protein homeostasis, or proteostasis network of cognitive and neuroplasticity process, as new model to explain the important effect on the neurophenotype of trisomy that occur not only in the loci of chromosome 21 but also in genes located in other chromosomes.

Management of the Organic Fraction of Municipal Solid Waste in the Context of a Sustainable and Circular Model: Analysis of Trends in Latin America and the Caribbean.

The main objective of this research is to analyze the most relevant aspects of the management of the organic fraction of municipal solid waste (OFMSW) and the Sustainable and Circular Production Models (SCPMs) in Latin America and the Caribbean (LAC). The bibliometric method was used for the analysis of 190 studies obtained from the Scopus and Latin America and The Caribbean on Health Sciences (LILACS) databases. The systematic review provided information on the main research approaches: identification and characterization; quantification; strategic and interdisciplinary management; and processes for treatment or valorization. Finally, an evaluation of public policies and strategies was performed. The results show that Brazil, Mexico, and Colombia have the highest number of publications on OFMSW. The findings also indicate that both research and policy strategies on SCPMs prioritize bioenergy and biofuels as the leading alternatives for the valorization of OFMSW. It also reflects the relevance of the Circular Economy (CE) and Bioeconomy (BE) as the main drivers of waste recovery and/or valorization in LAC. These aspects are of great interest to governments that are still in the process of implementing SCPMs. However, for those more advanced in this area, it provides valuable information on progress, policy effectiveness, and future actions for improvement.

Prescription Patterns of Drugs Given to Hospitalized COVID-19 Patients: A Cross-Sectional Study in Colombia.

The impact of COVID-19 prompted a race to find a treatment that would reduce its mortality. Most studies have not shown favorable results for many of these drugs, but they are still used. The aim as to determine the differences and similarities in the hospital pharmacological management of patients with COVID-19 according to sex, age group, and geographical region of Colombia, 2020-2021. Descriptive cross-sectional study was conducted on the prescription patterns of the medications given to patients diagnosed with COVID-19 treated in eight clinics in Colombia between 6 March 2020 and 31 May 2021. We performed a descriptive analysis of the sociodemographic, clinical, and pharmacological variables of the patients. A total of 8596 patients from 170 cities were identified, with a median age of 53.0 years and 53.3% of them men. A total of 24.3% required care in the intensive care unit, and 18.7% required invasive mechanical ventilation. The most commonly used drugs for the treatment of COVID-19 were systemic corticosteroids (63.6%), followed by colchicine (12.8%), azithromycin (8.9%), and ivermectin (6.4%). Corticosteroids, anticoagulants, colchicine, azithromycin, ivermectin, and hydroxychloroquine were prescribed more frequently in men, and their overall use increased with age. There were differences in prescriptions between geographic regions. The majority of patients were managed with medications included in the management guidelines. There were differences between sexes, age groups, and geographical regions.

Wound healing activity of the hydroalcoholic extract and the main metabolites of Amphipterygium adstringens (cuachalalate) in a rat excision model.

ETHNOPHARMACOLOGICAL RELEVANCE: The bark of Amphipterygium adstringens Schiede ex Schltdl (Anacardiaceae), commonly known as 'cuachalalate' has been used in Mexican traditional medicine for the treatment of skin and oral lesions, gastric ulcers, and other conditions. The use as wound healing of the bark of this plant has been known since before the Spanish conquest of Mexico. Its uses are mentioned in the first writings of the Spanish in the 16th century. It is important to highlight that its use for wound healing treatment has no scientific previous reports. AIM OF THE STUDY: The objectives of this study were to determine the wound healing effect of the hydroalcoholic extract of the stem bark of Amphipterygium adstringens and its main metabolites, using a model of excision in the back of Wistar rats. To evaluate its antimicrobial effect against common bacteria that living on the skin of wounds and to evaluate its effect on angiogenesis. MATERIALS AND METHODS: The hydroalcoholic extract of cuachalalate (HAE, 10 mg/wound/day), the 3α-hydroxymasticadienoic acid (3 MA, 300 µg/wound/day), the masticadienoic acid (MA, 300 µg/wound/day), and a mixture of anacardic acids (ANA, 300 µg per wound) were tested in a murine excision model topically for 15 days, to evaluate their wound-healing effect. The results were reported in a wound closure percentage (n = 30 animals per treatment curve), using pirfenidone (PIR, 8% in vehicle) as a reference drug. In addition, histologic analysis was performed to evaluate the structure and quality of the scar. The effect on angiogenesis was assessed using the chick embryo chorioallantoic membrane (CAM) model (n = 6 eggs per treatment). The concentration evaluated for each treatment was 300 µg, using as proangiogenic reference drug the histamine (HIS, 5.6 µg) and as antiangiogenic drugs pirfenidone (9 µg) and acetylsalicylic acid (ASA, 9 µg). The antimicrobial test was performed against S. mutans, S. aureus, P. aeruginosa y E. coli using a minimum inhibitory concentration (MIC) assay. RESULTS: The 3α-hydroxymasticadienoic (3 MA) acid and the anacardic acids (ANA) improve the wound closure by approximates 30% (similar to pirfenidone) in comparison with the control-treated with the vehicle in the proliferative phase. On the other hand, the hydroalcoholic extract of cuachalalate (HAE) did not show an effect on the wound healing process. The histologic analysis demonstrated that the three main metabolites showed an improvement in the scar structure. According to the CAM results, it is probable that the main action mechanism of the 3α-hydroxymasticadienoic acid and the anacardic acids is related to their proangiogenic effect. In addition, ANA showed a modest antimicrobial effect. CONCLUSIONS: The 3α-hydroxymasticadienoic acid and anacardic acids showed a better tissue structure and reduced the time closure of the wound. In addition, the anacardic acids showed antimicrobial effects and both metabolites promote angiogenesis, suggesting that these effects may be related to their action mechanism. These metabolites of cuachalalate could be a good alternative for wound healing treatment.