Hollow viscus perforation in blunt abdominal trauma: A 14-year experience from a trauma center.

BACKGROUND: Isolated perforations of hollow viscus (HV) represent less than 1% of injuries in blunt abdominal trauma (BAT). When they do present, they are generally due to high-impact mechanisms in the segments of the intestine that are fixed. The aim of this study is to determine the incidence of major HV injuries in BAT at the "Dr. Domingo Luciani" General Hospital (HDL), and address the literature gap regarding updated HV perforations following BAT, especially in low-income settings. METHODS: A retrospective review was conducted on the medical records of patients admitted to our trauma center with a diagnosis of complicated BAT with HV perforation over 14 years. RESULTS AND DISCUSSION: Seven hundred sixty-one patients were admitted under the diagnosis of BAT. Of them, 36.79% underwent emergency surgical resolution, and 6.04% had HV perforation as an operative finding. Almost half (44.44%) of these cases presented as a single isolated injury, while the remaining were associated with other intra-abdominal organ injuries. The most common lesions were Grade II-III jejunum and Grade I transverse colon, affecting an equal proportion of patients at 13.33%. In recent years, an increased incidence of HV injuries secondary to BAT has been observed. Despite this, in many cases, the diagnosis is delayed, so even in the presence of negative diagnostic studies, the surgical approach based on the trauma mechanism, hemodynamic status, and systematic reevaluation of the polytraumatized patient should prevail.

Translation and linguistic validation of 24 PROMIS item banks into French.

PURPOSE: The Patient-Reported Outcome Measurement Information System (PROMIS®) was developed to provide reliable, valid, and normed item banks to measure health. The item banks provide standardized scores on a common metric allowing for individualized, brief assessment (computerized adaptive tests), short forms (e.g. heart failure specific), or profile assessments (e.g. PROMIS-29). The objective of this study was to translate and linguistically validate 24 PROMIS adult item banks into French and highlight cultural nuances arising during the translation process. METHODS: We used the FACIT translation methodology. Forward translation into French by two native French-speaking translators was followed by reconciliation by a third native French-speaking translator. A native English-speaking translator fluent in French then completed a back translation of the reconciled version from French into English. Three independent reviews by bilingual translators were completed to assess the clarity and consistency of terminology and equivalency across the English source and French translations. Reconciled versions were evaluated in cognitive interviews for conceptual and linguistic equivalence. RESULTS: Twenty-four adult item banks were translated: 12 mental health, 10 physical health, and two social health. Interview data revealed that 577 items of the 590 items translated required no revisions. Conceptual and linguistic differences were evident for 11 items that required iterations to improve conceptual equivalence and two items were revised to accurately reflect the English source. CONCLUSION: French translations of 24 item banks were created for routine clinical use and research. Initial translation supported conceptual equivalence and comprehensibility. Next steps will include validation of the item banks.

Early queen infection shapes developmental dynamics and induces long-term disease protection in incipient ant colonies.

Infections early in life can have enduring effects on an organism's development and immunity. In this study, we show that this equally applies to developing 'superorganisms'--incipient social insect colonies. When we exposed newly mated Lasius niger ant queens to a low pathogen dose, their colonies grew more slowly than controls before winter, but reached similar sizes afterwards. Independent of exposure, queen hibernation survival improved when the ratio of pupae to workers was small. Queens that reared fewer pupae before worker emergence exhibited lower pathogen levels, indicating that high brood rearing efforts interfere with the ability of the queen's immune system to suppress pathogen proliferation. Early-life queen pathogen exposure also improved the immunocompetence of her worker offspring, as demonstrated by challenging the workers to the same pathogen a year later. Transgenerational transfer of the queen's pathogen experience to her workforce can hence durably reduce the disease susceptibility of the whole superorganism.

SCA8 RAN polySer protein preferentially accumulates in white matter regions and is regulated by eIF3F.

Spinocerebellar ataxia type 8 (SCA8) is caused by a bidirectionally transcribed CTG·CAG expansion that results in the in vivo accumulation of CUG RNA foci, an ATG-initiated polyGln and a polyAla protein expressed by repeat-associated non-ATG (RAN) translation. Although RAN proteins have been reported in a growing number of diseases, the mechanisms and role of RAN translation in disease are poorly understood. We report a novel toxic SCA8 polySer protein which accumulates in white matter (WM) regions as aggregates that increase with age and disease severity. WM regions with polySer aggregates show demyelination and axonal degeneration in SCA8 human and mouse brains. Additionally, knockdown of the eukaryotic translation initiation factor eIF3F in cells reduces steady-state levels of SCA8 polySer and other RAN proteins. Taken together, these data show polySer and WM abnormalities contribute to SCA8 and identify eIF3F as a novel modulator of RAN protein accumulation.

Oxytocin-like signaling in ants influences metabolic gene expression and locomotor activity.

Ants are emerging model systems to study cellular signaling because distinct castes possess different physiologic phenotypes within the same colony. Here we studied the functionality of inotocin signaling, an insect ortholog of mammalian oxytocin (OT), which was recently discovered in ants. In Lasius ants, we determined that specialization within the colony, seasonal factors, and physiologic conditions down-regulated the expression of the OT-like signaling system. Given this natural variation, we interrogated its function using RNAi knockdowns. Next-generation RNA sequencing of OT-like precursor knock-down ants highlighted its role in the regulation of genes involved in metabolism. Knock-down ants exhibited higher walking activity and increased self-grooming in the brood chamber. We propose that OT-like signaling in ants is important for regulating metabolic processes and locomotion.-Liutkeviciute, Z., Gil-Mansilla, E., Eder, T., Casillas-Pérez, B., Di Giglio, M. G., Muratspahic, E., Grebien, F., Rattei, T., Muttenthaler, M., Cremer, S., Gruber, C. W. Oxytocin-like signaling in ants influences metabolic gene expression and locomotor activity.

An ELISA for quantification of recombinant human EGF in production process samples, serum and urine.

A sandwich enzyme-linked immunosorbent assay for quantifying a recombinant human Epidermal Growth Factor (rhEGF) protein used in a vacunal preparation is described. The protein was detected with high specificity in a short incubation time at elevated temperature, the assay showing a linear range between 0.0625 and 1 ng/mL. According to the regression analysis for the dilutional linearity data, r2 = 0.9998, slope = 1.07 and intercept = 0.05 were obtained. The intra- and inter-assay coefficient of variation, ranged from 0.79 to 2.87% and 4.87-9.69% respectively demonstrating high reproducibility and precision. The ANOVA test used in the specificity/interference study revealed parallelism among curves (p > 0.1), which indicated lack of interference in the working range. Recovery obtained in accuracy test for three concentration levels varied between 89 and 111%; evidencing a reliable analytical assay to characterize the quality of the recombinant protein in the manufacturing process at large scale, and other biological matrixes as: urine and serum.

Surgical Repositioning of the Premaxilla Using a Minimally Invasive Endonasal Approach.

OBJECTIVE: The aim of this study was to evaluate a technique for the surgical repositioning of the premaxilla using a minimally invasive endonasal approach. DESIGN: Retrospective review of clinical records. SETTING: Tertiary care, University Hospital, pediatric maxillofacial surgery unit. PATIENTS: Twenty-one patients (12 boys and 9 girls), ages ranging from 6 to 21 years, with BCLP+A and premaxillary malposition (PM). INTERVENTIONS: Surgical repositioning of the premaxilla (SRP) using a minimally invasive endonasal approach, from November 2007 to November 2015. MAIN OUTCOME MEASURES: Achieving maxillary arch alignment and premaxillary stability was defined as treatment success. Intraoperative and postoperative complications were also recorded. RESULTS: In all cases (100%), the treatment was successful either at first surgery or after reoperation. Two patients (9.5%) were reoperated-one due to premaxillary instability and one due to PM relapse. There were no perioperative complications. CONCLUSIONS: SRP using a minimally invasive endonasal approach is a safe and effective technique that levels and aligns the maxillary arch in preparation for SABG, which minimizes the risk of wound infection and premaxillary vascular compromise. The endonasal approach improves tissue quality of the mucoperiosteal flaps when performing the SABG procedure. Further prospective studies are needed to elucidate the best protocols and techniques for the management of PM in patients with BCLP+ A.

Tamoxifen as a new therapeutic tool for neutrophilic lung inflammation.

BACKGROUND AND OBJECTIVE: Neutrophilic asthma is an important disease subgroup, including patients with severe phenotypes and erratic responses to standard treatments. Tamoxifen (TX), a selective estrogen receptor modulator (SERM) used as treatment of human breast cancer, has been shown to induce early apoptosis of equine blood and bronchoalveolar lavage fluid (BALF) neutrophils in vitro. Equine recurrent airway obstruction (RAO) is a naturally occurring neutrophilic condition, closely related with human asthma. Our purpose was to investigate the therapeutic potential of tamoxifen in horses with neutrophilic lung inflammation. METHODS: Twelve horses underwent acute lung inflammation through exposure to allergens known to cause RAO, after which they received treatment with either tamoxifen or dexamethasone. Outcome measures included evaluation of clinical signs, BALF cytology, and early apoptosis of blood and BALF neutrophils. RESULTS: Tamoxifen treatment decreased BALF neutrophil counts (65.3 ± 19.38% before treatment; 7.6 ± 4.5% 2 days post-treatment,; and 13.6 ± 9.3% 5 days post-treatment). A similar decrease was observed with dexamethasone treatment (48.6 ± 5.88% before treatment; 11.5 ± 8.1% 2 days post-treatment; 14.6 ± 10.3% 5 days post-treatment). Clinical and endoscopic scores improved in both treatment groups. Tamoxifen treatment significantly increased early apoptosis of peripheral blood neutrophils at 5 days post-treatment (27.04 ± 15.2%), and in BALF neutrophils at 2 and 5 days post-treatment (42.11 ± 11.67% and 48.98 ± 2.6%, respectively). CONCLUSION: Tamoxifen treatment in horses with induced acute pulmonary inflammation promoted early apoptosis of blood and BALF neutrophils, reduction in BALF neutrophils and improvement in the animals' clinical status.

In vivo human T cell engineering with enveloped delivery vehicles.

Viruses and virally derived particles have the intrinsic capacity to deliver molecules to cells, but the difficulty of readily altering cell-type selectivity has hindered their use for therapeutic delivery. Here, we show that cell surface marker recognition by antibody fragments displayed on membrane-derived particles encapsulating CRISPR-Cas9 protein and guide RNA can deliver genome editing tools to specific cells. Compared to conventional vectors like adeno-associated virus that rely on evolved capsid tropisms to deliver virally encoded cargo, these Cas9-packaging enveloped delivery vehicles (Cas9-EDVs) leverage predictable antibody-antigen interactions to transiently deliver genome editing machinery selectively to cells of interest. Antibody-targeted Cas9-EDVs preferentially confer genome editing in cognate target cells over bystander cells in mixed populations, both ex vivo and in vivo. By using multiplexed targeting molecules to direct delivery to human T cells, Cas9-EDVs enable the generation of genome-edited chimeric antigen receptor T cells in humanized mice, establishing a programmable delivery modality with the potential for widespread therapeutic utility.

Neuronal DNA repair reveals strategies to influence CRISPR editing outcomes.

Genome editing is poised to revolutionize treatment of genetic diseases, but poor understanding and control of DNA repair outcomes hinders its therapeutic potential. DNA repair is especially understudied in nondividing cells like neurons, which must withstand decades of DNA damage without replicating. This lack of knowledge limits the efficiency and precision of genome editing in clinically relevant cells. To address this, we used induced pluripotent stem cells (iPSCs) and iPSC-derived neurons to examine how postmitotic human neurons repair Cas9-induced DNA damage. We discovered that neurons can take weeks to fully resolve this damage, compared to just days in isogenic iPSCs. Furthermore, Cas9-treated neurons upregulated unexpected DNA repair genes, including factors canonically associated with replication. Manipulating this response with chemical or genetic perturbations allowed us to direct neuronal repair toward desired editing outcomes. By studying DNA repair in postmitotic human cells, we uncovered unforeseen challenges and opportunities for precise therapeutic editing.

p∆TubHA4C, a new versatile vector for constitutive expression in Drosophila.

Several vectors for gene expression are available in Drosophila, a hub for genetics and genomics innovation. However, the vectors for ubiquitous expression have a complex structure, including coding exons, that makes in-frame cloning of cDNAs very complicated. In this report we describe a new Drosophila expression vector (p∆TubHA4C) for ubiquitous expression of coding sequences under the control of a minimal 0.9 kb promoter of α1 tubulin (α1t). This plasmid was designed to include optimized multiple cloning sites (polylinker) to provide flexibility in cloning strategies. We also added the option of double labeling the expressed proteins with two C-terminal tags, the viral epitope hemagglutinin and a synthetic tetracysteine (4C) tag that binds small fluorescent compounds. This dual tag allows both in situ and biochemical detection of the desired protein. In particular, the new 4C tag technology combines easy fluorescent labeling with small arsenical compounds in live or fixed cells and tissues, while producing minimal alterations to the tagged protein due to its small size. To demonstrate the potent and ubiquitous expression under the control of the ∆Tub promoter, bacterial lacZ was expressed and monitored in cell culture and transgenic flies. We found that the modified 0.9 kb ΔTub promoter induced similar expression levels to the intact 2.6 kb α1t promoter, supporting the inclusion of all critical regulatory elements in the new and flexible ∆TubHA4C vector.

Dynamic pathogen detection and social feedback shape collective hygiene in ants.

Cooperative disease defense emerges as group-level collective behavior, yet how group members make the underlying individual decisions is poorly understood. Using garden ants and fungal pathogens as an experimental model, we derive the rules governing individual ant grooming choices and show how they produce colony-level hygiene. Time-resolved behavioral analysis, pathogen quantification, and probabilistic modeling reveal that ants increase grooming and preferentially target highly-infectious individuals when perceiving high pathogen load, but transiently suppress grooming after having been groomed by nestmates. Ants thus react to both, the infectivity of others and the social feedback they receive on their own contagiousness. While inferred solely from momentary ant decisions, these behavioral rules quantitatively predict hour-long experimental dynamics, and synergistically combine into efficient colony-wide pathogen removal. Our analyses show that noisy individual decisions based on only local, incomplete, yet dynamically-updated information on pathogen threat and social feedback can lead to potent collective disease defense.

A Technical Note of Improvement of the Elnady Technique for Tissue Preservation in Veterinary Anatomy.

Teaching veterinary anatomy has been subjected to changes and restrictions that have promoted the development of new techniques for preserving organs and cadavers. The Elnady technique is a recent method for the conservation of tissues. Specimens produced with this technique are realistic, durable, soft, and flexible, but an undesirable feature is the discoloration of tissues. In the present study, we describe modifications of the Elnady technique for organ and tissue preservation. Specimens were prepared on the theoretical basis of the Elnady technique, but at low temperatures and with longer durations for the fixation, dehydration, glycerin impregnation and curing processes. Furthermore, the tissues were pigmented with a red vegetable pigment before dehydration or in the glycerin impregnation process. The results show high-quality specimens with minimal shrinkage and natural color aspects. The modified Elnady technique is adequate for producing specimens of better contrast for education purposes.

Yellowing, Weathering and Degradation of Marine Pellets and Their Influence on the Adsorption of Chemical Pollutants.

Marine microplastics (MPs) are exposed to environmental factors, which produce aging, weathering, surface cracking, yellowing, fragmentation and degradation, thereby changing the structure and behavior of the plastic. This degradation also has an influence on the adsorption of persistent organic pollutants over the microplastic surface, leading to increased concentration with aging. The degradation state affects the microplastic color over time; this is called yellowing, which can be quantified using the Yellowness Index (YI). Weathering and surface cracking is also related with the microplastic yellowing, which can be identified by Fourier transform infrared spectroscopy (FTIR). In this study, the degradation state of marine microplastic polyethylene pellets with different aging stages is evaluated and quantified with YI determination and the analysis of FTIR spectrums. A color palette, which relates to the microplastic color and YI, was developed to obtain a visual percentage of this index. The relation with the adsorption rate of persistent organic pollutant over the microplastic surface was also determined.

Validation of the FACT-Gastric cancer quality of life questionnaire for use in Spanish-speaking countries.

OBJECTIVES: The purpose of this study was to validate a universal Spanish translation of the Functional Assessment of Cancer Therapy-Gastric Cancer (FACT-Ga; Version 4) questionnaire for use in Spanish-speaking countries. METHODS: Translation of the FACT-Ga from English to Spanish was accomplished by employing the Functional Assessment of Chronic Illness Therapy (FACIT) translation methodology, which utilizes a multinational team of translation experts. A single (universal) Spanish version of the questionnaire was developed for use with gastric cancer patients recruited from Argentina, Chile, Mexico, Peru, and Spain. Pretesting of the questionnaire was conducted using 75 cancer patients (15 from each country), who were also cognitively debriefed. RESULTS: Statistical analysis yielded marginal results for the Peru and Spain samples, although when analyzing pooled data from all five countries, statistics were within expected ranges. Qualitative analysis indicated that there were negligible linguistic concerns that impacted a very small proportion of the items. CONCLUSION: The universal Spanish FACT-Ga demonstrates content and linguistic validity, and is conceptually equivalent to its English source. It is a promising tool for use in evaluating the health-related quality of life for Spanish-speaking patients with gastrointestinal-related cancers, given more research regarding universally derived reliability and validity statistics.

Morphometrical Study of the Lumbar Segment of the Internal Vertebral Venous Plexus in Dogs: A Contrast CT-Based Study.

The internal vertebral venous plexus (IVVP) is a thin-walled, valveless venous network that is located inside the vertebral canal, communicating with the cerebral venous sinuses. The objective of this study was to perform a morphometric analysis of the IVVP, dural sac, epidural space and vertebral canal between the L1 and L7 vertebrae with contrast-enhanced computed tomography (CT). Six clinically healthy adult dogs weighing between 12 kg to 28 kg were used in the study. The CT venographic protocol consisted of a manual injection of 880 mgI/kg of contrast agent (587 mgI/kg in a bolus and 293 mgI/mL by continuous infusion). In all CT images, the dimensions of the IVVP, dural sac, and vertebral canal were collected. Dorsal reconstruction CT images showed a continuous rhomboidal morphological pattern for the IVVP. The dural sac was observed as a rounded isodense structure throughout the vertebral canal. The average area of the IVVP ranged from 0.61 to 0.74 mm2 between L1 and L7 vertebrae (6.3-8.9% of the vertebral canal), and the area of the dural sac was between 1.22 and 7.42 mm2 (13.8-72.2% of the vertebral canal). The area of the epidural space between L1 and L7 ranged from 2.85 to 7.78 mm2 (27.8-86.2% of the vertebral canal). This CT venography protocol is a safe method that allows adequate visualization and morphometric evaluation of the IVVP and adjacent structures.

Distribution and transport of microplastics in the upper 1150 m of the water column at the Eastern North Atlantic Subtropical Gyre, Canary Islands, Spain.

Nowadays it is widely known that pollution by microplastics (MP) at the open ocean covers immense areas. Buoyant plastics tend to accumulate in areas of convergence at the sea surface such as subtropical gyres, while non-buoyant plastics accumulate at the seafloor. However, previous studies have revealed that the total amount of plastic in the different oceans is not well correlated with the concentrations measured at the sea surface and the sea floor, evidencing a significant amount of missing plastic in the oceans. This deviation could be related to an underestimation of the role played by small fragments of plastic and fibers in the oceans. Furthermore, microplastic fragments with a density lower than the density of seawater have been gathered hundreds of meters below the sea surface in the Pacific Ocean due to their size and shape. The main objective of this study is to carry out, for the first time, an equivalent analysis along the water column for the Atlantic Ocean. In that sense, a total number of 51 samples were collected during four different oceanographic cruises between February and December 2019, from the sea surface down to 1150 m depth at the open ocean waters of the Canary Islands region (Spain). For each sample, 72 l of seawater were filtered on board with a mesh size of 100 µm, where the presence of microplastics has been clearly observed. Our results reveal the presence of microplastics at least up to 1150 m depth, at the Northeastern Atlantic Subtropical Gyre with noticeable seasonal differences. The spatial distribution of these small fragments and fibers at the water column is mainly related to the oceanic dynamics and mesoscale convective flows, overcoming the MP motion induced by their own buoyancy. Moreover, these microplastics have being transported by the ocean dynamics as passive drifters.

CCG•CGG interruptions in high-penetrance SCA8 families increase RAN translation and protein toxicity.

Spinocerebellar ataxia type 8 (SCA8), a dominantly inherited neurodegenerative disorder caused by a CTG•CAG expansion, is unusual because most individuals that carry the mutation do not develop ataxia. To understand the variable penetrance of SCA8, we studied the molecular differences between highly penetrant families and more common sporadic cases (82%) using a large cohort of SCA8 families (n = 77). We show that repeat expansion mutations from individuals with multiple affected family members have CCG•CGG interruptions at a higher frequency than sporadic SCA8 cases and that the number of CCG•CGG interruptions correlates with age at onset. At the molecular level, CCG•CGG interruptions increase RNA hairpin stability, and in cell culture experiments, increase p-eIF2α and polyAla and polySer RAN protein levels. Additionally, CCG•CGG interruptions, which encode arginine interruptions in the polyGln frame, increase toxicity of the resulting proteins. In summary, SCA8 CCG•CGG interruptions increase polyAla and polySer RAN protein levels, polyGln protein toxicity, and disease penetrance and provide novel insight into the molecular differences between SCA8 families with high vs. low disease penetrance.