Retorno laboral en pacientes con lesión medular traumática en un centro hospitalario de México / Return to work in patients with traumatic spinal cord injury in a medical center in Mexico

Antecedentes y objetivo El regreso a un empleo remunerado es uno de los resultados más importantes en cuanto a reintegración social después de una lesión medular traumática y un indicador de éxito de los programas de rehabilitación; a pesar del impacto que tiene, muy pocos estudios en México se han enfocado en medir la reintegración comunitaria de estos pacientes. El objetivo es analizar la situación laboral de los pacientes con medular traumática atendidos en un centro hospitalario en México. Materiales y métodos Estudio descriptivo-transversal. Pacientes trabajadores de 19-55 años con diagnóstico de lesión medular traumática atendidos en un centro hospitalario en México a los cuales se les realizó una encuesta telefónica. Resultados Se incluyeron 18 pacientes (15 hombres, 3 mujeres), con una edad promedio de 38 años (± 10,3). Los niveles de lesión más comunes fueron cervical y torácico; los grados de escala de Asia Impairment Scale más comunes fueron A y E; 17 pacientes recibieron rehabilitación al egreso; la escala Spinal Cord Independence Measure promedio fue de 65,22 (± 35,11). Cinco pacientes fueron recontratados después de la lesión (27,7%), en un periodo medio de tiempo de 7 meses (± 2,9). Principales factores relacionados a la reintegración laboral: edad joven, niveles más bajos de la lesión, ingreso a un programa de rehabilitación, alta puntuación en la escala Spinal Cord Independence Measure y estado civil casado o en unión libre. Conclusiones Este trabajo demuestra la poca reinserción laboral después de una lesión medular traumática, así como los factores que influyen para la misma, destacando la importancia de un programa adecuado de rehabilitación con un enfoque multidisciplinario (AU)

Background and objective One of the most important outcomes regarding social reintegration after a traumatic spinal cord injury is social reinsertion; despite its huge impact, very few studies in Mexico have measured community reintegration in these patients. The objective of this study was to analyse the working situation of patients with traumatic spinal cord injury at a hospital centre in Mexico. Material and methods Cross-sectional descriptive study. Working patients, aged 19-55 years, diagnosed with traumatic spinal cord injury at a hospital centre in Mexico were included; a telephone survey was performed. Results Eighteen patients were included (15 men, 3 women), with a mean age of 38 years (± 10.3). The most common levels of injury were cervical and thoracic; the most common Asia Impairment Scale grades were A and E; 17 patients were included at a rehabilitation programme at discharge; the average Spinal Cord Independence Measure score was 65.22 (± 35.11). Five patients were hired after the injury in a mean period of 7 months (± 2.9). The main factors associated with occupational reintegration were young age, lower injury levels, an adequate rehabilitation programme, high Spinal Cord Independence Measure scale score, and being married or cohabiting. Conclusion This study shows the low return to work rate after a traumatic spinal cord injury, as well as the main factorsa affecting it; highlighting the importance of an adeaquate rehabilitation program with a multidisciplinary approach (AU)

[Return to work in patients with traumatic spinal cord injury in a medical center in Mexico]. / Retorno laboral en pacientes con lesión medular traumática en un centro hospitalario de México.

BACKGROUND AND OBJECTIVE: One of the most important outcomes regarding social reintegration after a traumatic spinal cord injury is social reinsertion; despite its huge impact, very few studies in Mexico have measured community reintegration in these patients. The objective of this study was to analyse the working situation of patients with traumatic spinal cord injury at a hospital centre in Mexico. MATERIAL AND METHODS: Cross-sectional descriptive study. Working patients, aged 19-55 years, diagnosed with traumatic spinal cord injury at a hospital centre in Mexico were included; a telephone survey was performed. RESULTS: Eighteen patients were included (15 men, 3 women), with a mean age of 38 years (± 10.3). The most common levels of injury were cervical and thoracic; the most common Asia Impairment Scale grades were A and E; 17 patients were included at a rehabilitation programme at discharge; the average Spinal Cord Independence Measure score was 65.22 (± 35.11). Five patients were hired after the injury in a mean period of 7 months (± 2.9). The main factors associated with occupational reintegration were young age, lower injury levels, an adequate rehabilitation programme, high Spinal Cord Independence Measure scale score, and being married or cohabiting. CONCLUSION: This study shows the low return to work rate after a traumatic spinal cord injury, as well as the main factorsa affecting it; highlighting the importance of an adeaquate rehabilitation program with a multidisciplinary approach.

DNA dosimeter measurements of beam profile using a novel simultaneous processing technique.

A DNA dosimeter (DNAd) was previously developed that uses double-strand breaks (DSB) to measure dose. This dosimeter has been tested to measure dose in scenarios where transient-charged particle equilibrium (TCPE) has been established. The probability of double strand break (PDSBo), which is the ratio of broken double-stranded DNA (dsDNA) to the initial unbroken dsDNA in the dosimeter, was used to quantify DSBs and related to dose. The goal of this work is to produce a new technique to process and analyze the DNAd and quantify DNA-DSBs. This technique included simultaneously processing multiple DNAds and also establishing a new form to the probability of double strand break (PDSBn), which was then used to test the DNAd in a non-TCPE condition by taking beam penumbra measurements. The technique utilized a 384-well plate, and the measurements were made at the edge of a 10 × 10 cm field and compared to film measurements. During these penumbra measurements, while observing the positional differences in the higher gradient region at 4.1 and 4.55 cm from the center of the radiation field, the distance to agreement of PDSBo to film were 0.38 cm and 0.26 cm while the distance to agreement of PDSBn to film were 0.11 cm and 0.06 cm, respectively. Finally, the developed new separation technique reduced the time needed for the analysis of 25 samples from 200 min to 30 min.

Criterios Ergonómicos para el Diseño de Quirófanos / Ergonomic Criteria for Operating Room Design

Resumen El personal involucrado en el área quirúrgica se ve afectado con lesiones musculoesqueléticas por esfuerzos y movimientos repetitivos acumulados. La gravedad de sus lesiones está dada en función de las posturas de trabajo, la especialidad quirúrgica y la disposición de los elementos con los que interactúa. La ergonomía ha tomado relevancia ya que ha hecho aportes muy importantes para las condiciones de trabajo en diferentes áreas. Aun cuando en la literatura se pueden encontrar diversas investigaciones de la frecuencia y los efectos de las lesiones ocupacionales en el personal del área quirúrgica, escasos estudios han propuesto pautas para el diseño ergonómico de quirófanos. El presente estudio engloba cuatro criterios ergonómicos que deben considerarse para el diseño de quirófanos.

Abstract Personnel involved in the surgical area are affected with musculoskeletal injuries due to accumulated repetitive stress and movements. The severity of the injuries is given according to the work postures, the surgical specialty and the arrangement of the elements in the operating room. Ergonomics has become relevant since it has made very important contributions to working conditions in different areas. Although in the literature investigations of the frequency and effects of occupational injuries on surgical staff can be found, few studies have proposed guidelines for the ergonomic design of operating rooms. The present study encompasses four ergonomic criteria that should be considered for the design of operating rooms.

Characterization of a novel 3D printed patient specific phantom for quality assurance in cranial stereotactic radiosurgery applications.

In single-isocenter stereotactic radiosurgery/radiotherapy (SRS/SRT) intracranial applications, multiple targets are being treated concurrently, often involving non-coplanar arcs, small photon beams and steep dose gradients. In search for more rigorous quality assurance protocols, this work presents and evaluates a novel methodology for patient-specific pre-treatment plan verification, utilizing 3D printing technology. In a patient's planning CT scan, the external contour and bone structures were segmented and 3D-printed using high-density bone-mimicking material. The resulting head phantom was filled with water while a film dosimetry insert was incorporated. Patient and phantom CT image series were fused and inspected for anatomical coherence. HUs and corresponding densities were compared in several anatomical regions within the head. Furthermore, the level of patient-to-phantom dosimetric equivalence was evaluated both computationally and experimentally. A single-isocenter multi-focal SRS treatment plan was prepared, while dose distributions were calculated on both CT image series, using identical calculation parameters. Phantom- and patient-derived dose distributions were compared in terms of isolines, DVHs, dose-volume metrics and 3D gamma index (GI) analysis. The phantom was treated as if the real patient and film measurements were compared against the patient-derived calculated dose distribution. Visual inspection of the fused CT images suggests excellent geometric similarity between phantom and patient, also confirmed using similarity indices. HUs and densities agreed within one standard deviation except for the skin (modeled as 'bone') and sinuses (water-filled). GI comparison between the calculated distributions resulted in passing rates better than 97% (1%/1 mm). DVHs and dose-volume metrics were also in satisfying agreement. In addition to serving as a feasibility proof-of-concept, experimental absolute film dosimetry verified the computational study results. GI passing rates were above 90%. Results of this work suggest that employing the presented methodology, patient-equivalent phantoms (except for the skin and sinuses areas) can be produced, enabling literally patient-specific pre-treatment plan verification in intracranial applications.

BET protein proteolysis targeting chimera (PROTAC) exerts potent lethal activity against mantle cell lymphoma cells.

Bromodomain extraterminal protein (BETP) inhibitors transcriptionally repress oncoproteins and nuclear factor-κB (NF-κB) target genes that undermines the growth and survival of mantle cell lymphoma (MCL) cells. However, BET bromodomain inhibitor (BETi) treatment causes accumulation of BETPs, associated with reversible binding and incomplete inhibition of BRD4 that potentially compromises the activity of BETi in MCL cells. Unlike BETi, BET-PROTACs (proteolysis-targeting chimera) ARV-825 and ARV-771 (Arvinas, Inc.) recruit and utilize an E3-ubiquitin ligase to effectively degrade BETPs in MCL cells. BET-PROTACs induce more apoptosis than BETi of MCL cells, including those resistant to ibrutinib. BET-PROTAC treatment induced more perturbations in the mRNA and protein expressions than BETi, with depletion of c-Myc, CDK4, cyclin D1 and the NF-κB transcriptional targets Bcl-xL, XIAP and BTK, while inducing the levels of HEXIM1, NOXA and CDKN1A/p21. Treatment with ARV-771, which possesses superior pharmacological properties compared with ARV-825, inhibited the in vivo growth and induced greater survival improvement than the BETi OTX015 of immune-depleted mice engrafted with MCL cells. Cotreatment of ARV-771 with ibrutinib or the BCL2 antagonist venetoclax or CDK4/6 inhibitor palbociclib synergistically induced apoptosis of MCL cells. These studies highlight promising and superior preclinical activity of BET-PROTAC than BETi, requiring further in vivo evaluation of BET-PROTAC as a therapy for ibrutinib-sensitive or -resistant MCL.

Novel BET protein proteolysis-targeting chimera exerts superior lethal activity than bromodomain inhibitor (BETi) against post-myeloproliferative neoplasm secondary (s) AML cells.

The PROTAC (proteolysis-targeting chimera) ARV-825 recruits bromodomain and extraterminal (BET) proteins to the E3 ubiquitin ligase cereblon, leading to degradation of BET proteins, including BRD4. Although the BET-protein inhibitor (BETi) OTX015 caused accumulation of BRD4, treatment with equimolar concentrations of ARV-825 caused sustained and profound depletion (>90%) of BRD4 and induced significantly more apoptosis in cultured and patient-derived (PD) CD34+ post-MPN sAML cells, while relatively sparing the CD34+ normal hematopoietic progenitor cells. RNA-Seq, Reverse Phase Protein Array and mass cytometry 'CyTOF' analyses demonstrated that ARV-825 caused greater perturbations in messenger RNA (mRNA) and protein expressions than OTX015 in sAML cells. Specifically, compared with OTX015, ARV-825 treatment caused more robust and sustained depletion of c-Myc, CDK4/6, JAK2, p-STAT3/5, PIM1 and Bcl-xL, while increasing the levels of p21 and p27. Compared with OTX015, PROTAC ARV-771 treatment caused greater reduction in leukemia burden and further improved survival of NSG mice engrafted with luciferase-expressing HEL92.1.7 cells. Co-treatment with ARV-825 and JAK inhibitor ruxolitinib was synergistically lethal against established and PD CD34+ sAML cells. Notably, ARV-825 induced high levels of apoptosis in the in vitro generated ruxolitinib-persister or ruxolitinib-resistant sAML cells. These findings strongly support the in vivo testing of the BRD4-PROTAC based combinations against post-MPN sAML.

Aminolevulinic acid dendrimers in photodynamic treatment of cancer and atheromatous disease.

The use of endogenous protoporphyrin IX after administration of 5-aminolaevulinic acid (ALA) has led to many applications in photodynamic therapy (PDT). We have previously reported that the conjugation of ALA dendrimers enhances porphyrin synthesis. The first aim of this work was to evaluate the ability of ALA dendrimers carrying 6 and 9 ALA residues (6m-ALA and 9m-ALA) to photosensitise cancer cells. For this aim, we employed LM3 mammary carcinoma cells. In these tumour cells, at low concentrations porphyrin synthesis from dendrimers was higher compared to ALA, whereas at high concentrations, porphyrin synthesis was similar from both compounds. Topical application of ALA dendrimers on the skin overlying a subcutaneous LM3 implanted tumour showed no diffusion of the molecules either to distant skin sites or to the adjacent tumour, suggesting a promising use of the ALA macromolecules in superficial cancer models. As a second objective, we proposed the use of ALA-dendrimers in vascular PDT for the treatment of atherosclerosis. Thus, we focused our studies on ALA-dendrimer's selectivity towards macrophages in comparison with endothelial cells. For this aim we employed Raw 264.7 macrophages and HMEC-1 microvasculature cells. Porphyrin synthesis induced in macrophages by 6m-ALA and 9m-ALA (3 h, 0.025 mM) was 6 and 4.6 times higher respectively compared to the endothelial cell line, demonstrating the high affinity of ALA dendrimers for macrophages. On the other hand, ALA employed at low concentrations was slightly selective (1.7-fold) for macrophages. Inhibition studies suggested that ALA dendrimer uptake in macrophages is mainly mediated by caveloae-mediated endocytosis. Our main conclusion is that in addition to being promising molecules in PDT of superficial cancer, ALA dendrimers may also find applications in vascular PDT, since in vitro they showed selectivity to the macrophage component of the atheromatous plaque, as compared to the vascular endothelium.

Treatment with melatonin after onset of experimental uveitis attenuates ocular inflammation.

BACKGROUND AND PURPOSE: Uveitis is a prevalent intraocular inflammatory disease and one of the most damaging ocular conditions. Pretreatment with melatonin prevented ocular inflammation induced by an intravitreal injection of bacterial LPS in the Syrian hamster. Here, we have assessed the anti-inflammatory effects of melatonin administered after the onset of ocular inflammation. EXPERIMENTAL APPROACH: The eyes of male Syrian hamsters were intravitreally injected with vehicle or LPS. Melatonin was injected i.p. every 24 h, starting 12 or 24 h after the LPS injection. A clinical evaluation (with a score index based on clinical symptoms), the number of infiltrating cells, protein concentration and PGE2 and PGF2α levels in the aqueous humour, as well as retinal NOS activity, lipid peroxidation and TNF-α levels were assessed. Retinal function was assessed by scotopic electroretinography, and light microscopy and immunohistochemistry were used to evaluate the state of the retinal structure. KEY RESULTS: Both treatment regimens with melatonin decreased clinical symptoms, reduced the leakage of cells and proteins, and decreased PG levels in aqueous humour from eyes injected with LPS. In addition, melatonin treatment blocked the decrease in scotopic electroretinogram a- and b-wave amplitude, protected the retinal structure and reduced the increase in NOS activity, lipid peroxidation and TNF-α levels, induced by LPS. CONCLUSIONS AND IMPLICATIONS: These results indicate that treatment with melatonin, starting after the onset of uveitis, attenuated ocular inflammation induced by LPS in the Syrian hamster and support the use of melatonin as a therapeutic resource for uveitis treatment.

Photodynamic inactivation of Gram-positive bacteria employing natural resources.

The aim of this paper was to investigate a collection of plant extracts from Argentina as a source of new natural photosensitizers (PS) to be used in Photodynamic Inactivation (PDI) of bacteria. A collection of plants were screened for phototoxicity upon the Gram-positive species Staphylococcus epidermidis. Three extracts turned out to be photoactive: Solanum verbascifolium flower, Tecoma stans flower and Cissus verticillata root. Upon exposure to a light dose of 55J/cm(2), they induced 4, 2 and 3logs decrease in bacterial survival, respectively. Photochemical characterisation of S. verbascifolium extract was carried out. PDI reaction was dependent mainly on singlet oxygen and to a lesser extent, on hydroxyl radicals, through type II and I reactions. Photodegradation experiments revealed that the active principle of the extract was not particularly photolabile. It is noticeable that S. verbascifolium -PDI was more efficient under sunlight as compared to artificial light (total eradication vs. 4 logs decrease upon 120min of sunlight). The balance between oxidant and antioxidant compounds is likely to be masking or unmasking potential PS of plant extracts, but employing the crude extract, the level of photoactivity of S. verbascifolium is similar to some artificial PS upon exposure to sunlight, demonstrating that natural resources can be employed in PDI of bacteria.

New insights into clinical trial for Colostrinin in Alzheimer's disease.

BACKGROUND: The pathomechanism of Alzheimer's disease (AD) is multifactorial although the most popular hypotheses are centered on the effects of the misfolded, aggregated protein, amyloid beta (Abeta) and on Tau hyperphosphorylation. OBJECTIVES: Double blinded clinical trials were planned to demonstrate the effect of Colostrinin (CLN) on instrumental daily activities of AD patients. The potential molecular mechanisms by which CLN mediates its effects were investigated by gene expression profiling. METHODS: RNAs isolated from CLN-treated cells were analyzed by high-density oligonucleotide arrays. Network and pathway analyses were performed using the Ingenuity Pathway Analysis software. RESULTS: The Full Sample Analysis at week 15 showed a stabilizing effect of CLN on cognitive function in ADAS-cog (p = 0.02) and on daily function in IADL (p = 0.02). The overall patient response was also in favor of CLN (p = 0.03). Patients graded as mild on entry also showed a superior response of ADAS-cog compared to more advanced cases (p = 0.01). Data derived from microarray network analysis show that CLN elicits highly complex and multiphasic changes in the cells' transcriptome. Importantly, transcriptomal analysis showed that CLN alters gene expression of molecular networks implicated in Abeta precursor protein synthesis, Tau phosphorylation and increased levels of enzymes that proteolitically eliminate Abeta. In addition, CLN enhanced the defense against oxidative stress and decreased expression of inflammatory chemokines and cytokines, thereby attenuating inflammatory processes that precede Alzheimer's and other neurological diseases. CONCLUSION: Together these data suggest that CLN has promising potential for clinical use in prevention and therapy of Alzheimer's and other age-associated central nervous system diseases.

H2S and volatile fatty acids elimination by biofiltration: clean-up process for biogas potential use.

In the present work, the main objective was to evaluate a biofiltration system for removing hydrogen sulfide (H(2)S) and volatile fatty acids (VFAs) contained in a gaseous stream from an anaerobic digestor (AD). The elimination of these compounds allowed the potential use of biogas while maintaining the methane (CH(4)) content throughout the process. The biodegradation of H(2)S was determined in the lava rock biofilter under two different empty bed residence times (EBRT). Inlet loadings lower than 200 g/m(3)h at an EBRT of 81 s yielded a complete removal, attaining an elimination capacity (EC) of 142 g/m(3)h, whereas at an EBRT of 31 s, a critical EC of 200 g/m(3)h was reached and the EC obtained exhibited a maximum value of 232 g/m(3)h. For 1500 ppmv of H(2)S, 99% removal was maintained during 90 days and complete biodegradation of VFAs was observed. A recovery of 60% as sulfate was obtained due to the constant excess of O(2) concentration in the system. Acetic and propionic acids as a sole source of carbon were also evaluated in the bioreactor at different inlet loadings (0-120 g/m(3)h) obtaining a complete removal (99%) for both. Microcosms biodegradation experiments conducted with VFAs demonstrated that acetic acid provided the highest biodegradation rate.

Nitrosation of melatonin by nitric oxide: a computational study.

Melatonin is being increasingly promoted as a therapeutic agent for the treatment of jet lag and insomnia, and is an efficient free radical scavenger. We have recently characterized a product for the reaction of melatonin with nitric oxide (NO), N-nitrosomelatonin. In the present work, reaction pathways with N1, C2, C4, C6 and C7 as possible targets for its reaction with NO that yield the respective nitroso derivatives have been investigated using semiempirical AM1 computational tools, both in vacuo and aqueous solution. Specifically, two different pathways were studied: a radical mechanism involving the hydrogen atom abstraction to yield a neutral radical followed by NO addition, and an ionic mechanism involving addition of nitrosonium ion to the indolic moiety. Our results show that the indolic nitrogen is the most probable site for nitrosation by the radical mechanism, whereas different targets are probable considering the ionic pathway. These results are in good agreement with previous experimental findings and provide a coherent picture for the interaction of melatonin with NO.

Circadian activity of the GABAergic system in the golden hamster retina.

Daily changes in gamma-aminobutyric acid (GABA) turnover rate were studied in the golden hamster retina. This parameter showed significant variations throughout the light-dark cycle, with minimal values during the day. Retinal glutamic acid decarboxylase (GAD) activity was higher at midnight than at noon. Moreover, [3H]GABA binding significantly varied throughout the 24-h cycle, with maximal values during the day. Saturation studies performed at 12:00 and 24:00 h indicated that the maximal concentration of [3H]GABA binding sites (Bmax) was significantly higher at noon, whereas the dissociation constant (Kd) remained unchanged. High K+-induced GABA release was significantly higher at midnight than at midday. Daily variations in retinal GABA turnover rate, GABA release, and in its specific binding persisted in golden hamsters exposed to constant darkness. In summary, these results support the idea of a circadian clock-controlled GABAergic activity in the hamster retina.

Luxación glenohumeral posterior inveterada / Locked posterior shoulder dislocation

Se presenta un caso clínico de luxación glenohumeral posterior inveterada. Se analizan los métodos diagnósticos Y terapéuticos utilizados, así como el resultado funcional obtenido. Se revisan los aspectos relacionados con el diagnóstico y tratamiento de dicha lesión. Las luxaciones glenohumerales posteriores conforman una patología poco frecuente, de diagnóstico tardío y que aboca a un tratamiento quirúrgico en pacientes con limitación articular o en edad activa. Se trata de un paciente varón de 46 años de edad, con antecedentes de traumatismo por caída sobre hombro derecho seis semanas antes, que consulta por gran limitación de rango de movilidad articular y dolor mecánico. El TAC demostró luxación glenohumeral posterior. Se realizó una reparación quirúrgica de la lesión mediante técnica de Hawkins-Neer. La evolución postoperatoria fue satisfactoria y el resultado funcional en el momento del alta definitiva, transcurridos tres meses, fue excelente. Se consiguió una movilidad rotacional y abducción prácticamente completas, con ausencia casi total de dolor mecánico (AU)