Mitochondrial genome engineering coming-of-age.

The mitochondrial genome has been difficult to manipulate because it is shielded by the organelle double membranes, preventing efficient nucleic acid entry. Moreover, mitochondrial DNA (mtDNA) recombination is not a robust system in most species. This limitation has forced investigators to rely on naturally occurring alterations to study both mitochondrial function and pathobiology. Because most pathogenic mtDNA mutations are heteroplasmic, the development of specific nucleases has allowed us to selectively eliminate mutant species. Several 'protein only' gene-editing platforms have been successfully used for this purpose. More recently, a DNA double-strand cytidine deaminase has been identified and adapted to edit mtDNA. This enzyme was also used as a component to adapt a DNA single-strand deoxyadenosine deaminase to mtDNA editing. These are major advances in our ability to precisely alter the mtDNA in animal cells.

Destigmatizing perceptions about Black adolescent depression: randomized controlled trial of brief social contact-based video interventions.

OBJECTIVE: To test the utility of brief social contact-based video interventions of a Black adolescent girl to reduce stigmatized attitudes and increase help-seeking intentions around adolescent depression. METHODS: We conducted a randomized controlled trial (RCT) with 14- to18-year-old healthy volunteers drawn from the general US population. We enrolled participants through a crowdsourcing platform (n = 1,093) and randomly assigned participants to one of three video conditions (117 s each): depressed (DEP); depressed, adjusted to aspects unique to being a Black adolescent girl (including experienced or internalized racism; ADJ); and control (CONT). The primary outcome was the Depression Stigma Scale (DSS); secondary outcomes were the General Health-Seeking Questionnaire (GHSQ), and thermometers for Black and white race perception "warmth". RESULTS: Following the intervention, the DSS changed from baseline across the three conditions (p < .001). ADJ outperformed both DEP (p = .031) and CONT (p < .001). A race-by-intervention interaction (p < .001) revealed different response profiles between Black (ADJ = DEP = CONT; p = .726) and non-Black participants (ADJ > DEP > CONT; p < .001). DEP and ADJ both resulted in higher treatment-seeking intentions for both the emotional problems and the suicidal thought subscales of the GHSQ. We found a race-by-intervention interaction (p = .01) for the Black thermometer, which revealed a significant 2° increase in warmth among white (p < .001), but not Black, viewers (p = .06). CONCLUSIONS: On a short-term basis, brief social contact-based videos proved effective among adolescents in reducing depression-related stigma, increasing help-seeking intentions, and providing an "empathic foothold" in the lives of racially stigmatized groups. Even as the enduring effects of these interventions remain to be determined, the deployment on social media of short videos opens new opportunities to reach a large number of at-risk youth."

Oocyte maturation in the toad Rhinella arenarum (Amphibia, Anura): Evidence of cAMP involvement in steroid production and action.

In this work, we describe the participation of the adenylate cyclase/3'-5'-cyclic adenonsine monophosphate (cAMP) pathway in the seasonal follicular secretion of progesterone (P4 ) and testosterone (T), and its relationship with the maturation of Rhinella arenarum oocytes. Under gonadotropin stimulation, P4 secretion was the dominant steroid produced during the reproductive period, resulting in 100% germinal vesicle breakdown (GVBD) in oocytes in vitro; in contrast, T and estradiol (E2 ) secretion increased (∼16 nM/20 follicles and ∼80 pM/20 follicles, respectively) during the non-reproductive period, but only yielded 50% GVBD. Treatment of the follicles with dibutyryl-cAMP or forskolin induced a significant increase in T secretion during both periods, but P4 secretion did not significantly change and GVBD did not occur. These results suggest that high cAMP levels in the oocyte maintain meiotic arrest and prevent the induction effect of follicular steroids. An increase in cAMP levels in denuded oocytes, however, negatively regulated T-induced maturation since treatment with increasing db-cAMP or forskolin inhibited their maturation. Therefore, we hypothesize that an elevation in T during the non-reproductive period favors its aromatization to E2 , leading to follicle growth. During the reproductive period, P4 production might promote oocyte maturation when environmental conditions are favorable for reproduction. Together, the results indicate that steroidogenesis is seasonal and depends on gonadotropic activity in R. arenarum.

[Repair of perirradicular tissues in non-surgical endodontic treatment. A review]. / Reparación de tejidos perirradiculares en el tratamiento endodóntico no quirúrgico. Una revisión.

Introduction: Non-surgical endodontic treatment aims to prevent apical periodontitis, achieved with the disinfection of the root canal system. Additionally, there are pathologies where the toxic content of the canal goes to the periradicular tissues, causing osteolysis or lesions of the bone tissue that are radiographically observed as radiolucent images. When the endodontic treatment is successful, the repair of these lesions occurs over time. Aim: To analyze the periradicular repair process of non-surgical endodontic treatment and the factors that affect it. Materials and Methods: An electronic search was carried out using the search engines PUBMED, Scopus, Google Academic, and Scielo with the words "Non-Surgical Endodontic Treatment," "Periapical Tissues," "Biological Repair," "Apical Repair." Factors such as incomplete texts, PDF texts, and publication date of the article were considered, including data from the last five (05) years. Results: The information reviewed comprised 236 articles analyzed with the inclusion and exclusion criteria, and only 42 articles met these criteria. Conclusion: The success of endodontic treatment lies in the absence of clinical and radiographic signs and symptoms of infection; this is achieved with a good application of clinical protocols and procedures focused on the disinfection of the root canal system, from diagnosis, biomechanical preparation, and disinfection of the root canal system with irrigating substances and filling, including coronal rehabilitation from an aesthetic and/or prosthetic point of view.

Transforming Science Research Through Liberatory Race-conscious Mentorship: The BUILD PODER Professional Development Modules.

BUILD is a NIH initiative designed to retain underrepresented undergraduates in biomedicine. Of the 10 BUILD sites, BUILD PODER is the only space-and-place that approaches this initiative through the framework of critical race theory (CRT). A feature of BUILD PODER's path to student empowerment is liberatory race-conscious mentorship. Researchers developed, implemented, and evaluated a quintipartite CRT-based antiracist-anticolonial online training program for biomedical educators nationwide. We review the social scientific and historical knowledge used to create these novel mentorship training modules. We describe the modular content and activities. We also report evaluation data obtained during beta-testing and outline how this information helped finalize the product. Discussed are the individual- and institutional-level implications of modularizing the developmental process of liberatory race consciousness.

mitoTALEN reduces the mutant mtDNA load in neurons.

Mutations within mtDNA frequently give rise to severe encephalopathies. Given that a majority of these mtDNA defects exist in a heteroplasmic state, we harnessed the precision of mitochondrial-targeted TALEN (mitoTALEN) to selectively eliminate mutant mtDNA within the CNS of a murine model harboring a heteroplasmic mutation in the mitochondrial tRNA alanine gene (m.5024C>T). This targeted approach was accomplished by the use of AAV-PHP.eB and a neuron-specific synapsin promoter for effective neuronal delivery and expression of mitoTALEN. We found that most CNS regions were effectively transduced and showed a significant reduction in mutant mtDNA. This reduction was accompanied by an increase in mitochondrial tRNA alanine levels, which are drastically reduced by the m.5024C>T mutation. These results showed that mitochondrial-targeted gene editing can be effective in reducing CNS-mutant mtDNA in vivo, paving the way for clinical trials in patients with mitochondrial encephalopathies.

Changes in the mechanical properties of chemically treated bovine pericardium after a short uniaxial cyclic test.

The mechanical behavior of calf pericardium, a biomaterial utilized in the manufacture of cardiac bioprostheses, in response to a short tensile cyclic test has been evaluated. The trial involved 120 samples cut longitudinally or transversely, subjected to 10 cycles until a stress of between 1 and 3 MPa was reached. Tests of hardness and tear propagation were performed, and the results were compared with a control series. The energy loss was also computed, and it was approximately 10-fold greater in the first cycle than the loss in the subsequent nine cycles. Despite this singularity, they correlated very precisely. The effect of the direction in which the tissue is cut on energy loss was not significant nor the difference between hardness prior to and after testing. The results of the tear propagation tests gave no statistical differences prior to and after testing. From the obtained results, it seems that the test carried out does not affect significantly the mechanical properties of calf pericardium.

A Hero's Journey: Supporting children throughout inpatient psychiatric hospitalization using a therapeutic comic book.

PROBLEM: Art- and narrative-based interventions are an integral component of pediatric inpatient psychiatric care. We describe a novel therapeutic comic book we developed for hospitalized children and young adolescents. METHODS: A Hero's Journey is a 38-page zine that can be freely downloaded and photocopied for distribution. The short booklet is intended to demystify and offer guidance throughout the experience of hospitalization, promote interaction and socialization, provide scaffolding for skill-building, and prepare patients for moving forward after discharge. FINDINGS: The underlying foundations of the booklet include: 1) Theoretical sources (Joseph Campbell's hero's journey; Donald Schön's reflective practice; and the principles of narrative medicine); and 2) Clinical sources (collaborative problem solving; cognitive-behavioral therapy, and trauma-informed care). We articulate how each page relates to the different components, and how individual pages can be used as worksheets for practice of specific skills. We next provide suggestions on how best to use the booklet: from arrival at the emergency room, through inpatient hospitalization, and toward discharge. We also propose ways for staff, caregivers, and any child-facing adult to make use of this clinical resource in support of a patient's recovery and reintegration into their community. CONCLUSIONS: Even though not yet empirically tested, this therapeutic comic book is available for dissemination free of cost. We encourage leaders in nursing and therapeutic recreation to try using this resource in their emergency room and milieu settings.

[Lingual frenectomy with ND:YAG laser. case report]. / Frenectomía lingual con láser ND:YAG. reporte de caso.

Ankyloglossia is considered a congenital patology, whose treatment indicated is a frenectomy, this surgical technique consists in remove the tissue that joins the tongue with the floor mouth. This technique allows the patient a considerable improvement to limitations caused by this anomaly such as difficulties in suction, pronunciation, chewing and difficulty in touching the lower lip with the tip of the tongue. Currently the use of laser technology and its benefits in modern dentistry, allows the realization of surgical procedures free of bleeding, with very little pain and inflammation of the tissues and with a recovery time much lower than necessary with conventional techniques. The present clinical case, show a 12-year-old patient with severe ankyloglossia, lingual frenectomy was indicated. A contact Nd: YAG laser was used, achieving a surgical intervention with little pain, free bleeding and without suture.

Current status on cyclotron facilities and related infrastructure supporting PET applications in Latin America and the Caribbean.

This review presents the results of a survey conducted by the International Atomic Energy Agency on cyclotrons and related infrastructure used for radionuclide and radiopharmaceutical production which are supporting PET imaging applications in Latin America and the Caribbean region.

[Use of diagnostic modalities for dentofacial imaging in forensic dentistry. Literature review]. / Uso de las modalidades diagnósticas pertenecientes a la imagenología dentofacial en la odontología forense. Revisión de la literatura.

Objective: To describe the use of diagnostic modalities for dentofacial imaging in forensic dentistry. Materials and Methods: A scientific search was carried out in the PubMed, Google Academic, and SciELO databases with the keywords "Dentofacial Imaging", "Panoramic Radiography", "Lateral Cephalogram", "Cone Beam Computed Tomography (CBCT)", "Digital Radiography", and "Forensic Dentistry". Forty-eight recently dated articles published in English were selected, seeking information to describe the use of diagnostic modalities pertaining to dentofacial imaging in forensic dentistry. Results: The most relevant diagnostic modalities of dentofacial imaging for forensic dentistry include panoramic radiography, lateral skull radiography, posterior-anterior skull radiography and cone beam computed tomography. Conclusions: The modalities described, together with morphometric analyses, allow forensic dentists to identify a corpse, estimate age, sex, and even facilitate forensic facial reconstruction for identification purposes.

[Skull-facial anthropometric traits of forensic odontological interest for estimating sex, race and age. Review of the literature]. / Rasgos antropométricos craneofaciales de interés odontológico forense en la estimación de sexo, grupo étnico y edad. Revisión de la literatura.

One of the main functions of anthropologists and forensic dentists is to identify subjects according to physical characteristics of the features presented using non-routine methods. These characteristics, especially bone, allow professional to determine the sex, age and racial origin of the remains or skeleton found. Dentist focus on features belonging to the stomatognathic system, while anthropologists study the bones that make up the human body. In this study, we describe the investigations of cranio-facial anthropometric features of dental interest carried out by anthropologists to identify the sex, race and age of skeletal remains or skeletons. in addition, we describe the so-called dental anthropology that studies the elements of the stomatognathic system from an anthropological point of view. Electronic literature was reviewed through search engines such as PUBMED, Google Academic and SciELO with the search terms "Forensic Dentistry, Forensic Anthropology, Sex Determination, Ancestry Determination and Age Determination". Knowledge of the craniofacial anthropological features from the forensic point of view is of great importance in individualized and multidisciplinary studies by forensic dentists and anthropologists in the identification of skeletal remains.

Biocompatibility and calcification of bovine pericardium employed for the construction of cardiac bioprostheses treated with different chemical crosslink methods.

The use of biological materials in the construction of bioprostheses requires the application of different chemical procedures to improve the durability of the material without producing any undesirable effects. A number of crosslinking methods have been tested in biological tissues composed mainly of collagen. The aim of this study was to evaluate the in vitro biocompatibility, the mechanical properties, and in vivo calcification of chemically modified bovine pericardium using glutaraldehyde acetals (GAAs) in comparison with glutaraldehyde (GA) treatment. Homsy's tests showed that the most cytotoxic treatment is GA whereas GAA treatments showed lower cytotoxicity. Regarding the mechanical properties of the modified materials, no significant differences in stress at rupture were detected among the different treatments. Zeta-Potential showed higher negative values for GA treatment (-4.9 +/- 0.6 mV) compared with GAA-0.625% (-2.2 +/- 0.5 mV) and GAA-1% (-2.2 +/- 0.4 mV), which presented values similar to native tissue. Similar results were obtained for calcium permeability coefficients which showed the highest values for GA treatment (0.12 +/- 0.02 mm(2)/min), being significantly lower for GAA treatments or non-crosslinked pericardium. These results confirmed the higher propensity of the GA-treated tissues for attraction of calcium cations and were in good agreement with the calcification degree obtained after 60 days implantation into young rats, which was significantly higher for the GA group (22.70 +/- 20.80 mg/g dry tissue) compared with GAA-0.625% and GAA-1% groups (0.49 +/- 0.28 mg/g dry tissue and 3.51 +/- 3.27 mg/g dry tissue, respectively; P < 0.001). In conclusion, GAA treatments can be considered a promising alternative to GA treatment.

Propagation of tears in pericardium from young bulls: influence of the suture.

The tearing of the collagen fibers of biological materials utilized in implants or bioprostheses is an important, and sometimes early cause of the failure of these devices. We studied the force necessary to propagate a tear in a biomaterial, pericardium from young bulls, and the influence of the suture. An Elmendorf pendulum capable of measuring the force necessary to tear a given length of tissue was employed. We analyzed 112 trials (70%) that proved valid after achieving the homogeneity of the samples according to their thickness, thus making the results comparable. Mean forces ranging between 19.87 and 150 N were required to propagate tears measuring from 0.25 to 2.0 cm. In the samples with a 1-cm-long suture, sewn using an edge-to-edge technique, the propagation of the tear required a mean force of 15.75 N when the suture was made of nylon and 28.73 N when Prolene was utilized. When these results were compared with the mean recorded in an unsutured control series (56.76 N), the loss of resistance was significant in both sutured series (P = 0.000 and P = 0.011, respectively). Finally, the equation that relates the force (y) with the length of the tear made in unsutured tissue (x) was also obtained: y = 58.14 + 9.62x(2) (R(2) = 0.924). The force necessary to produce a microtear, thus estimated, can be utilized as a parameter for comparison.

[Recomendations for the prevention of adverse drug reactions in older adults with dementia]. / Recomendaciones en la prevención de reacciones adversas a medicamentos en personas mayores con demencia.

The elderly are one of the groups at greatest risk for adverse drugs reactions (ADR). The mean prevalence of these reactions in this population is 30%. Dementia is not an independent risk factor of ADR, but is the main condition that increases all risk factors (polypharmacy, comorbidity, inappropriate prescribing, drug-drug interactions, advanced age, and treatment adherence). The present article discusses revised and consensual recommendations for the prevention of ADR in the elderly, as well as recommendations specifically for dementia patients in relation to the management of comorbidity and cognitive, behavioral and psychological symptoms.

[Psychosocial factors and work place depression: a review]. / Factores psicosociales y depresión laboral: una revisión.

It is predicted that the depression will be the first cause of labor retirement and the second most frequent illness in the 2020 in developed countries. The consequences of depression affect the physical, mental, emotional and social well-being of the individuals, in the same way it generates serious blows to the economy of the companies where depressed patients with depression work; companies have to pay treatments also and the production decrease with the disability of workers suffering depression. The psychosocial factors play an important role as variables of risk or modulators in the development of this disorder. The objective is to carry out a review of the recent literature focus on the psychosocial factors and its relationship with the depression at the place of work. We consider that it is important to know the diagnosis of depression at the place of work, and determine the risk factors for recommendation of a specific treatment.

Caracterización epidemiológica de pacientes con síndrome posterior a resección anterior baja de recto y aproximación de su relación con aspectos demográficos, patológicos y quirúrgicos, en un centro de referencia en Medellín, entre 2016-2022 / Epidemiological characterization of patients with post-low anterior rectal resection syndrome and approximation of its relationship with demographic, pathological, and surgical aspects, in a referral center in Medellin, between 2016-2022

Introducción. El cáncer colorrectal es uno de los tipos de cáncer más comunes y mortales a nivel mundial. Aunque los avances médicos han mejorado el manejo, la cirugía sigue siendo fundamental. La resección anterior baja (RAB) de recto ha ganado relevancia, a pesar de que puede llevar al síndrome de resección anterior baja de recto (LARS, por sus siglas en inglés), afectando la calidad de vida. Métodos. Estudio de corte transversal con intención analítica en un centro de referencia en Medellín, Colombia. Los pacientes con cáncer de recto sometidos a RAB entre enero de 2016 y diciembre de 2022 completaron el cuestionario LARS para evaluar disfunción intestinal. Se evaluaron factores relacionados con la presencia de LARS por medio de un análisis bivariado. Resultados. De 234 pacientes elegibles, 110 (47 %) respondieron la encuesta, predominantemente mujeres (58,2 %). La edad promedio fue 62 años. Dos tercios de los pacientes recibieron neoadyuvancia y el 69 % requirieron ileostomía. La prevalencia de LARS fue 47,3 %. El 80,9 % llevaban más de 12 meses desde la cirugía o el cierre del estoma. Factores estadísticamente significativos asociados a LARS fueron edad mayor de 65 años (p=0,03), estadío patológico avanzado (p=0,02) y requerimiento de estoma (p=0,03). Conclusiones. El LARS afecta a casi la mitad de los pacientes en diferentes etapas posquirúrgicas. El LARS scorees una herramienta práctica para evaluar la función intestinal en el seguimiento del paciente. La prevalencia y los factores de riesgo identificados contribuyen a la comprensión del impacto de la cirugía conservadora del esfínter en la calidad de vida de los pacientes.

Introduction. Colorectal cancer is one of the most common and deadly types of cancer worldwide, with a high incidence of rectal cancer. Although medical advances have improved management, surgery remains crucial. Low anterior resection of the rectum (LAR) has gained significance, despite its potential to lead to low anterior resection syndrome (LARS), affecting quality of life. Methods. A cross-sectional study with analytical intent was conducted at a referral center in Medellín, Colombia. Patients with rectal cancer who underwent LAR between January 2016 and December 2022 completed the LARS questionnaire to assess intestinal dysfunction. Factors related to the presence of LARS were analyzed using bivariate analysis. Results. Of 234 eligible patients, 110 (47%) responded, predominantly women (58.2%). The average age was 62 years. Two-thirds of patients received neoadjuvant therapy and 69% required ileostomy. The prevalence of LARS was 47.3%. 80.9% had been more than 12 months post-surgery or stoma closure. Statistically significant factors associated with LARS included age over 65 years (p=0.03), advanced pathological stage (p=0.02), and stoma requirement (p=0.03). Conclusions. LARS affects almost half of the patients in various post-surgical stages. The LARS score is a practical tool for assessing intestinal function in patient follow-up. The prevalence and risk factors identified contribute to the understanding of the impact of sphincter-conserving surgery on patients' quality of life.

Determination of the force necessary for the propagation of tears in ostrich and calf pericardium.

The durability of prosthetic heart valve leaflets made of biological materials is limited. A tear in the biomaterial accelerates their early failure, but microtearing of the collagen fibers may be responsible for their medium-term failure. We studied the force necessary to propagate tearing in two biomaterials: ostrich and calf pericardium. One hundred twenty samples of each tissue were tested in an Elmendorf pendulum capable of measuring the force required to tear a tissue in which a predefined slit had been made. The forces required to produce tears, ranging between 2.5 and 0.25 cm in length, were determined. For ostrich pericardium, this force ranged between 67.67 and 4.80 newton, while that required to tear the same lengths of calf pericardium ranged between 70.67 and 4.70 newton. The function that relates the tearing force to the length of the tear was expressed as follows: y = 20.62x + 1.77x(2) (R(2) = 0.923) for ostrich pericardium and y = 45.57x - 7.21x(2) (R(2) = 0.936) for calf pericardium, where y is the force in newton and x is the length in centimeter. Calf pericardium was found to have a greater resistance to tearing. However, these results should be interpreted with caution owing to the fact that the thickness of the majority of the samples of ostrich pericardium was significantly less than that of calf pericardium. A more careful selection and utilization of adult ostrich pericardium would probably improve these results.

Validation of Electrochemiluminiscence Immunoassay for Ovarian Steroid Determination in Rhinella arenarum.

In this work, we describe the validation of an electrochemiluminescence immunoassay (ECLIA) that allowed us for the first time to determine the levels of progesterone (P4 ) and testosterone (T) secreted by Rhinella arenarum follicles during the preovulatory (POP) and reproductive (RP) periods. We also verified the relation between P4 and T levels and oocyte maturation. Moreover, we demonstrated that the extraction protocol developed for the determinations of P4 and T by ECLIA proved to be efficient and reproducible since the efficacy of the extraction was above 95% in all assays conducted. The results indicate that in the validation process the variation coefficient (CV) between assays is compatible with the analytical procedures based on automated immunoassays (CV < 8%) and that the adaptation proposed for the samples allows the determination of T and P4 with the Cobas e-411 analyzer. Our results indicate that in basal conditions the levels of T released by R. arenarum follicles were higher than those of P4 during POP and RP. In these conditions, steroid secretion failed to induce germinal vesicle break down (GVBD) in the follicles. Under gonadotropin stimulation, steroidogenesis showed a remarkable increase in both periods, especially during POP. This increase was correlated with a high maturation percentage in the follicles incubated in vitro (GVBD = 72 ± 16%) during POP. During RP, human Chorionic Gonadotropin (hCG) induced 81.75 ± 9.1% GVBD. This study is the first report of the seasonal steroidogenic activity in the ovary of R. arenarum in situ using an ECLIA-modified protocol developed in our laboratory.