Technology Readiness Level Roadmap for Developing Innovative Herbal Medicinal Products.

Despite the vast global botanical diversity, the pharmaceutical development of herbal medicinal products (HMPs) remains underexploited. Of over 370,000 described plant species, only a few hundred are utilized in HMPs. Most of these have originated from traditional use, and only a minority come from megadiverse countries. Exploiting the pharmacological synergies of the hundreds of compounds found in poorly studied plant species may unlock new therapeutic possibilities, enhance megadiverse countries' scientific and socio-economic development, and help conserve biodiversity. However, extensive constraints in the development process of HMPs pose significant barriers to transforming this unsatisfactory socio-economic landscape. This paper proposes a roadmap to overcome these challenges, based on the technology readiness levels (TRLs) introduced by NASA to assess the maturity of technologies. It aims to assist research entities, manufacturers, and funding agencies from megadiverse countries in the discovery, development, and global market authorization of innovative HMPs that comply with regulatory standards from ANVISA, EMA, and FDA, as well as WHO and ICH guidelines.

Assessment, distribution, and ecological risk of contaminants of emerging concern in a surface water-sediment-fish system impacted by wastewater.

The presence of contaminants of emerging concern in aquatic ecosystems represents an ever-increasing environmental problem. Aquatic biota is exposed to these contaminants, which can be absorbed and distributed to their organs. This study focused on the assessment, distribution, and ecological risk of 32 CECs in a Spanish river impacted by effluents from a wastewater treatment plant, analyzing the organs and plasma of common carp. Environmental concentrations in water and sediment were examined at sites upstream and downstream of the wastewater treatment plant. The two downstream sites showed 15 times higher total concentrations (12.4 µg L-1 and 30.1 µg L-1) than the two upstream sites (2.08 µg L-1 and 1.66 µg L-1). Half of the CECs were detected in fish organs, with amantadine having the highest concentrations in the kidney (158 ng g-1 w.w.) and liver (93 ng g-1 w.w.), followed by terbutryn, diazepam, and bisphenol F in the brain (50.2, 3.82 and 1.18 ng g-1 w.w.). The experimental bioaccumulation factors per organ were compared with the bioconcentration factors predicted by a physiologically based pharmacokinetic model, obtaining differences of one to two logarithmic units for most compounds. Risk quotients indicated a low risk for 38 % of the contaminants. However, caffeine and terbutryn showed an elevated risk for fish. The mixed risk quotient revealed a medium risk for most of the samples in the three environmental compartments: surface water, sediment, and fish.

Ivermectin antiviral activity against Varicellovirus bovinealpha 1: assessment of intracellular drug accumulation in virus-infected cells.

Varicellovirus bovinealpha 1 (formerly bovine alphaherpesvirus type 1, BoAHV-1) is associated with several syndromes in cattle, including respiratory disease and is one of the main agents involved in the bovine respiratory disease complex (BRDC). Its infectious cycle is characterized by latent infections with sporadic virus reactivation and transmission. Although the acute disease can be prevented by the use of vaccines, specific therapeutic measures are not available. Ivermectin (IVM) is a semi-synthetic avermectin with a broad-spectrum antiparasitic activity, which has previously shown to have potential as an antiviral drug. In this study, IVM antiviral activity against BoAHV-1 was characterized in two cell lines (MDBK [Madin Darby bovine kidney] and BT [bovine turbinate]), including the measurement of intracellular drug accumulation within virus-infected cells. IVM antiviral activity was assessed at three different drug concentrations (1.25, 2.5 and 5 µM) after incubation for 24, 48 and 72 h. Slight cytotoxicity was only observed with 5 µM IVM. Even the lowest IVM dose was able to induce a significant reduction in virus titers in both cell lines. These findings indicate that the antiviral effects of IVM were evident in our experimental model within the range of concentrations achievable through therapeutic in vivo administration. Consequently, additional in vivo trials are necessary to validate the potential utility of these results in effectively managing BoAHV-1 in infected cattle.

Developing Evidence for Equitable Assessment Characteristics Based on Clinical Learner Preferences Using Discrete Choice Experiments.

PURPOSE: Medical education is only beginning to explore the factors that contribute to equitable assessment in clinical settings. Increasing knowledge about equitable assessment ensures a quality medical education experience that produces an excellent, diverse physician workforce equipped to address the health care disparities facing patients and communities. Through the lens of the Anti-Deficit Achievement framework, the authors aimed to obtain evidence for a model for equitable assessment in clinical training. METHOD: A discrete choice experiment approach was used which included an instrument with 6 attributes each at 2 levels to reveal learner preferences for the inclusion of each attribute in equitable assessment. Self-identified underrepresented in medicine (UIM) and not underrepresented in medicine (non-UIM) (N = 306) fourth-year medical students and senior residents in medicine, pediatrics, and surgery at 9 institutions across the United States completed the instrument. A mixed-effects logit model was used to determine attributes learners valued most. RESULTS: Participants valued the inclusion of all assessment attributes provided except for peer comparison. The most valued attribute of an equitable assessment was how learner identity, background, and trajectory were appreciated by clinical supervisors. The next most valued attributes were assessment of growth, supervisor bias training, narrative assessments, and assessment of learner's patient care, with participants willing to trade off any of the attributes to get several others. There were no significant differences in value placed on assessment attributes between UIM and non-UIM learners. Residents valued clinical supervisors valuing learner identity, background, and trajectory and clinical supervisor bias training more so than medical students. CONCLUSIONS: This study offers support for the components of an antideficit-focused model for equity in assessment and informs efforts to promote UIM learner success and guide equity, diversity, and inclusion initiatives in medical education.

Spanish adaptation of the Burden Assessment Scale in family caregivers of people diagnosed with borderline personality disorder.

BACKGROUND: Caregiving is a strong source of stress and leads the family caregiver to experience the burden of being responsible for the care of a severely mentally ill family member. The Burden Assessment Scale (BAS) assesses burden in family caregivers. This study aimed to analyze the psychometric properties of the BAS in a sample of family caregivers of people diagnosed with Borderline Personality Disorder (BPD). METHODS: Participants were 233 Spanish family caregivers (157 women and 76 men aged between 16-76 years old, M = 54.44, SD = 10.09) of people diagnosed with BPD. The BAS, the Multicultural Quality of Life Index, and the Depression Anxiety Stress Scale-21 were used. RESULTS: An exploratory analysis resulted in a three-factor 16-item model (Disrupted Activities; Personal and Social Dysfunction; Worry, Guilt, and Being Overwhelmed) with an excellent fit (χ2(101) = 56.873, p = 1.000, CFI = 1.000, TLI = 1.000, RMSEA = .000, SRMR = .060), good internal consistency (ω = .93), a negative correlation with quality of life, and a positive correlation with anxiety, depression, and stress. CONCLUSION: The model obtained for the BAS is a valid, reliable, and useful tool for assessing burden in family caregivers of relatives diagnosed with BPD.

Occurrence, data-based modelling, and risk assessment of emerging contaminants in an alluvial aquifer polluted by river recharge.

This research presents the occurrence and fate of 121 contaminants of emerging concern (CECs) in an urban aquifer polluted by river recharge through a data-base modelling. Afterwards, risk quotients (RQs) are computed to determine the risk posed by CECs to human health. To this end, groundwater and river water samples were collected in four campaigns conducted from February to May 2021. Results show that 46 CECs are ubiquitous in groundwater and their concentrations vary several orders of magnitude, ranging from below the limit of quantification to 44.5·103 ng/L for iopamidol. Transformation products (TPs) are usually detected at lower concentrations than those of the parent substances but there are some exceptions (i.e., fipronil sulphide, fipronil sulfone and O-desmethylvenlafaxine). River concentrations are higher than those detected in groundwater for some CECs, indicating the occurrence of natural attenuation processes when river water infiltrates the aquifer. A data-based advection-reaction modelling is proposed and tested for ca. 40 substances with detection frequencies higher than 90%. It provides useful quantitative information regarding the dynamic behaviour of the variables monitored, expressed in terms of characteristic length, entropy and synchronized state contribution. Finally, risk quotients (RQs) are used to assess the human health risk posed by the ubiquitous CECs in groundwater. Most CECs do not pose any risk to the different life stages considered, as the RQs evaluated are lower than 0.01. However, the pharmaceuticals valsartan and its TP valsartan acid show RQs higher than 1, indicating that these substances might be harmful to human beings.

[Medical Care of people living with HIV in the Instituto Mexicano del Seguro Social]. / Atención a personas que viven con el VIH en el IMSS.

Infection by the human immunodeficiency virus (HIV) is apublic health problem worldwide, however, the incidence has remained relatively stable. In Mexico, around 10,000 new cases are reported each year. The Instituto Mexicano del Seguro Social (IMSS) has been a pioneer in the care of people living with HIV (PLWHA), gradually incorporating the different antiretroviral drugs (ARV). The first ARV used at the institutional level was zidovudine, in the 1990s, and later other agents were incorporated, such as protease inhibitors, drugs from the group of non-nucleoside analogs, and integrase inhibitors. In 2020, the migration to ARV schemes coformulated in a single tablet based on integrase inhibitors, which constitute a highly effective option and timely supply of drugs has been achieved in 99% of the population. In the aspect of prevention, the IMSS has also been a pioneer by being the first institution to implement HIV pre-exposure prophylaxis in 2021 at the national level and since 2022 universal post-exposure prophylaxis is available. The IMSS continues to be at the forefront incorporating the use of different management tools and instruments for the benefit of the population living with HIV. This document summarizes the history of HIV in the IMSS from the beginning of the epidemic to the present time.

La infección por el virus de la inmunodeficiencia humana (VIH) es un problema de salud pública a nivel mundial, sin embargo, la incidencia ha permanecido relativamente estable. En México se informa de alrededor de 10,000 casos nuevos al año. El Instituto Mexicano del Seguro Social (IMSS) ha sido pionero en la atención a las personas que viven con el VIH (PVV), incorporando paulatinamente los diferentes medicamentos antirretrovirales (ARV). El primer ARV utilizado a nivel institucional fue la zidovudina, en la década de los noventa, y posteriormente fueron incorporados otros agentes como los inhibidores de la proteasa, los medicamentos del grupo de los análogos no nucleósidos y los inhibidores de la integrasa. En el año 2020 ocurrió la migración a esquemas de ARV coformulados en una sola tableta a base de inhibidores de la integrasa, que constituyen una opción de alta eficacia y se ha logrado el surtimiento oportuno de los fármacos en el 99% de la población. En el aspecto de la prevención, el IMSS también ha sido pionero al ser la primera institución en implementar la profilaxis preexposición de VIH en el año 2021 a nivel nacional y desde el año 2022 se dispone de la profilaxis postexposición universal. El IMSS continúa a la vanguardia incorporando el uso de diferentes herramientas e instrumentos de gestión para beneficio de la población que vive con el VIH. En el presente documento se sintetiza la historia del VIH en el IMSS desde los inicios de la epidemia hasta el momento actual.

Using Bayesian networks for environmental health risk assessment.

The study investigated the potential relationships between air pollution, socio-economy, and proven pathologies (e.g., respiratory, cardiovascular) within an industrial area in Southern France (Etang de Berre), gathering steel industries, oil refineries, shipping, road traffic and experiencing a Mediterranean climate. A total of 178 variables were simultaneously integrated within a Bayesian model at intra-urban scale. Various unsupervised and supervised algorithms (maximum spanning tree, tree-augmented naive classifier) as well as sensitivity analyses were used to better understand the links between all variables, and highlighted correlations between population exposure to air pollutants and some pathologies. Adverse health effects (bronchus and lung cancers for 15-65 years old people) were observed for hydrofluoric acid at low background concentration (<0.003 µg m-3) while exposure to particulate cadmium (0.210-0.250 µg m-3) disrupts insulin metabolism for people over 65 years-old leading to diabetes. Bronchus and lung cancers for people over 65 years-old occurred at low background SO2 concentration (6 µg m-3) below European limit values. When benzo[k]fluoranthene exceeded 0.672 µg m-3, we observed a high number of hospital admissions for respiratory diseases for 15-65 years-old people. The study also revealed the important influence of socio-economy (e.g., single-parent family, people with no qualification at 15 years-old) on pathologies (e.g., cardiovascular diseases). Finally, a diffuse polychlorinated biphenyl (PCB) pollution was observed in the study area and can potentially cause lung cancers.

Psychological assessment of parents of people diagnosed with borderline personality disorder and comparison with parents of people without psychological disorders.

Background: To date, several evidence-based interventions have been created to help relatives of people with Borderline Personality Disorder (BPD), but few studies have analyzed the clinical situation of the family members. The aim of this study was twofold: (1) to explore the clinical symptomatology in a sample of parents of people diagnosed with BPD and compare them with a sample of a sample of people without a relative with a personality disorder, (2) to explore whether the parents of people diagnosed with BPD have psychopathology related to personality disorders (PD) or meet the diagnostic criteria for PD. Method: Participants were 42 (39.6%) fathers and 64 (60.4%) were mothers and mothers (n = XX, −%) of people diagnosed with BPD, who were selected from a specialized PD unit for treatment. The sample of people without a relative with a PD was obtained from social network announcements. To test for differences between the two groups, Student's t tests were performed for quantitative variables, and Chi-square tests were performed for categorical variables. Cohen's d was calculated as a measure of the effect size. Results: Parents of people with BPD showed greater depressive and anxious symptomatology, higher levels of expressed emotion, and worse quality of life than the sample of people without a relative with a personality disorder. In addition, a high percentage of the parents of people diagnosed with BPD (50%) met the diagnostic criteria for different PD. Conclusion: Parents of people diagnosed with BPD may need psychological help in various aspects. Therapists are therefore advised to bear in mind the importance of carrying out a psychological assessment of family members and, if necessary, to offer psychological intervention. It is crucial to invite the family to be part of the treatment, since they can be part of the solution.Clinical Trial registration: ClinicalTrials.gov ID, NCT04160871 (registered November 15, 2019).

Comparison between handheld ultrasound and regional and whole-body dual energy x-ray absorptiometry (DXA) for body fat assessment.

OBJECTIVES: To determine the extent of agreement between a handheld ultrasound (US) attached to an android tablet and the reference method dual energy x-ray absorptiometry (DXA) for the measurement of adiposity. METHODS: A whole-body DXA scan and abdominal adipose tissue thickness measurements using a handheld US were obtained from 104 adults (63 females, 41 males). Body fat percent (BF%), total fat mass (kg), and trunk fat mass (kg) were obtained from DXA. Subcutaneous adipose tissue (SAT), superficial subcutaneous adipose tissue (SSAT), and deep subcutaneous adipose tissue (DSAT) thickness were obtained from US. Sex-specific total fat mass, trunk fat mass, and BF% estimates by US were compared with DXA. Spearman's correlations and Bland-Altman plots were used to assess agreement between the methods. RESULTS: US SAT correlated strongly with total fat mass for both females (rs = 0.74) and males (rs = 0.87) as did trunk fat mass (females, rs = 0.81; males, rs = 0.83); as did SSAT and DSAT (females: rs = 0.65 and rs = 0.66; males: rs = 0.63 and rs = 0.85, respectively, all p-values < 0.0001). Bland-Altman plots demonstrated strong agreement for total and trunk fat mass for both males and females. For BF%, acceptable limits of agreement were observed for males but not for females, substantial proportional bias as indicated by a negative slope was noted for BF% using SAT (r = -0.298, p = 0.0177). CONCLUSION: The handheld US and technique to analyze abdominal adipose tissue thickness showed strong agreement with DXA results and generated highly comparable estimates for total and trunk fat mass for both sexes.

Total Lesion Glycolysis Improves Tumor Burden Evaluation and Risk Assessment at Diagnosis in Hodgkin Lymphoma.

Hodgkin lymphoma (HL) is a hematological malignancy with an excellent prognosis. However, we still need to identify those patients that could experience failed standard frontline chemotherapy. Tumor burden evaluation and standard decisions are based on Ann Arbor (AA) staging, but this approach may be insufficient in predicting outcomes. We aim to study new ways to assess tumor burden through volume-based PET parameters to improve the risk assessment of HL patients. We retrospectively analyzed 101 patients with HL from two hospitals in the Balearic Islands between 2011 and 2018. Higher metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were significantly associated with a higher incidence of III-IV AA stages, B-symptoms, hypoalbuminemia, lymphopenia, and higher IPS. Standardized uptake value (SUVmax) was significantly related to AA stage and hypoalbuminemia. We found that TLG or the combination of SUVmax, TLG, and MTV significantly improved the risk assessment when compared to AA staging. We conclude that TLG is the best single PET/CT-related tumor-load parameter that significantly improves HL risk assessment when compared to AA staging. If confirmed in a larger and validated sample, this information could be used to modify standard frontline therapy and justifies the inclusion of TLG inside an HL prognostic score.

Ecotoxicological risk assessment of wastewater irrigation on soil microorganisms: Fate and impact of wastewater-borne micropollutants in lettuce-soil system.

The implementation of the new Water Reuse regulation in the European Union brings to the forefront the need to evaluate the risks of using wastewater for crop irrigation. Here, a two-tier ecotoxicological risk assessment was performed to evaluate the fate of wastewater-borne micropollutants in soil and their ecotoxicological impact on plants and soil microorganisms. To this end, two successive cultivation campaigns of lettuces were irrigated with wastewater (at agronomical dose (not spiked) and spiked with a mixture of 14 pharmaceuticals at 10 and 100 µg/L each) in a controlled greenhouse experiment. Over the two cultivation campaigns, an accumulation of PPCPs was observed in soil microcosms irrigated with wastewater spiked with 100 µg/L of PPCPs with the highest concentrations detected for clarithromycin, hydrochlorothiazide, citalopram, climbazole and carbamazepine. The abundance of bacterial and fungal communities remained stable over the two cultivation campaigns and was not affected by any of the irrigation regimes applied. Similarly, no changes were observed in the abundance of ammonium oxidizing archaea (AOA) and bacteria (AOB), nor in clade A of commamox no matter the cultivation campaign or the irrigation regime considered. Only a slight increase was detected in clade B of commamox bacteria after the second cultivation campaign. Sulfamethoxazole-resistant and -degrading bacteria were not impacted either. The irrigation regimes had only a limited effect on the bacterial evenness. However, in response to wastewater irrigation the structure of soil bacterial community significantly changed the relative abundance of Acidobacteria, Chloroflexi, Verrucomicrobia, Beta-, Gamma- and Deltaprotebacteria. Twenty-eight operational taxonomic units (OTUs) were identified as responsible for the changes observed within the bacterial communities of soils irrigated with wastewater or with water. Interestingly, the relative abundance of these OTUs was similar in soils irrigated with either spiked or non-spiked irrigation solutions. This indicates that under both agronomical and worst-case scenario the mixture of fourteen PPCPs had no effect on soil bacterial community.

Removal of diclofenac by a local bacterial consortium: UHPLC-ESI-MS/MS analysis of metabolites and ecotoxicity assessment.

Diclofenac (DCF) belongs to the class of nonsteroidal anti-inflammatory drugs, which is one of the most consumed by population and detected in raw sewage. Several studies have reported variable removal rates by biodegradation of diclofenac in wastewater treatment plants (WWTPs). This study deals with the evaluation of the biodegradation of DCF by a bacterial consortium (obtained from pure cultures of Enterobacter hormaechei D15 and Enterobacter cloacea D16), which were isolated from household compost and Algerian WWTP, respectively, as sole carbon source and by co-metabolism, using glucose as carbon source. A 98% removal rate of DCF was observed when it is used as the sole carbon source, whilst only 44% of DCF was removed in co-metabolic conditions. Two metabolites were identified using ultra-high-performance liquid chromatography coupled to electrospray injection tandem mass spectrometry analysis (UHPLC-ESI-MS/MS); one of them was identified as 4'-hydroxy-DCF, and the second metabolite was suspected to be a nitro derivative of DCF, according to comparison with the literature. Biodegradation of DCF by this bacterial consortium generates relatively safe final by-products.

A Narrative Study of Equity in Clinical Assessment Through the Antideficit Lens.

PURPOSE: Efforts to address inequities in medical education are centered on a dialogue of deficits that highlight negative underrepresented in medicine (UIM) learner experiences and lower performance outcomes. An alternative narrative explores perspectives on achievement and equity in assessment. This study sought to understand UIM learner perceptions of successes and equitable assessment practices. METHOD: Using narrative research, investigators selected a purposeful sample of self-identified UIM fourth-year medical students and senior-level residents and conducted semistructured interviews. Questions elicited personal stories of achievement during clinical training, clinical assessment practices that captured achievement, and equity in clinical assessment. Using re-storying and thematic analysis, investigators coded transcripts and synthesized data into themes and representative stories. RESULTS: Twenty UIM learners (6 medical students and 14 residents) were interviewed. Learners often thought about equity during clinical training and provided personal definitions of equity in assessment. Learners shared stories that reflected their achievements in patient care, favorable assessment outcomes, and growth throughout clinical training. Sound assessments that captured achievements included frequent observations with real-time feedback on predefined expectations by supportive, longitudinal clinical supervisors. Finally, equitable assessment systems were characterized as sound assessment systems that also avoided comparison to peers, used narrative assessment, assessed patient care and growth, trained supervisors to avoid bias, and acknowledged learner identity. CONCLUSIONS: UIM learners characterized equitable and sound assessment systems that captured achievements during clinical training. These findings guide future efforts to create an inclusive, fair, and equitable clinical assessment experience.

Pharmaceuticals in a Mediterranean Basin: The influence of temporal and hydrological patterns in environmental risk assessment.

Occurrence of pharmaceuticals in the aquatic environment is nowadays a well-established issue that has become a matter of both scientific and public concern. Tons of different classes of pharmaceuticals find their way to the environment at variable degrees, after their use and excretion through wastewater and sewage treatment systems. The main goal of this study was to correlate the dynamics and the environmental risk of pharmaceuticals with different temporal and hydrological patterns, at the Guadiana Basin (South of Portugal). Water samples were collected bimonthly during 2017 (classified as a drought year) and 2018 (post-drought year) in: Zebro, Álamos and Amieira (intermittent hydrological streams), and Lucefécit (perennial hydrological stream). The pharmaceuticals quantified in higher concentrations, out of 27 investigated, were diclofenac (up to 4806 ng L-1), ibuprofen (3161 ng L-1), hydrochlorothiazide (2726 ng L-1) and carbamazepine (3223 ng L-1). Zebro and Álamos presented the highest contamination by this group of environmental hazardous substances, which may be correlated with the presence of wastewater treatment plants upstream the sampling point of each stream. Furthermore, the highest concentrations occurred mainly during the dry period (2017), when the flow was nearly inexistent in Zebro, and in Álamos after the first heavy rainfalls. In specific periods, the high concentrations of pharmaceuticals detected may induce risk for the organisms of lowest trophic levels, damaging the balance of the ecosystems at these streams. The risk quotient optimised approach (RQf) integrating exposure, toxicity and persistence factors, ranks the pharmaceuticals investigated in terms of risk for the aquatic ecosystems as follows: diclofenac, ibuprofen and carbamazepine (high risk), clarithromycin (moderate risk), acetaminophen, ofloxacin and bezafibrate (endurable risk), and hydrochlorothiazide (negligible risk).

Use of geographic indicators of healthcare, environment and socioeconomic factors to characterize environmental health disparities.

BACKGROUND: An environmental health inequality is a major public health concern in Europe. However just few studies take into account a large set of characteristics to analyze this problematic. The aim of this study was to identify and describe how socioeconomic, health accessibility and exposure factors accumulate and interact in small areas in a French urban context, to assess environmental health inequalities related to infant and neonatal mortality. METHODS: Environmental indicators on deprivation index, proximity to high-traffic roads, green space, and healthcare accessibility were created using the Geographical Information System. Cases were collected from death certificates in the city hall of each municipality in the Nice metropolitan area. Using the parental addresses, cases were geocoded to their census block of residence. A classification using a Multiple Component Analysis following by a Hierarchical Clustering allow us to characterize the census blocks in terms of level of socioeconomic, environmental and accessibility to healthcare, which are very diverse definition by nature. Relation between infant and neonatal mortality rate and the three environmental patterns which categorize the census blocks after the classification was performed using a standard Poisson regression model for count data after checking the assumption of dispersion. RESULTS: Based on geographic indicators, three environmental patterns were identified. We found environmental inequalities and social health inequalities in Nice metropolitan area. Moreover these inequalities are counterbalance by the close proximity of deprived census blocks to healthcare facilities related to mother and newborn. So therefore we demonstrate no environmental health inequalities related to infant and neonatal mortality. CONCLUSION: Examination of patterns of social, environmental and in relation with healthcare access is useful to identify census blocks with needs and their effects on health. Similar analyzes could be implemented and considered in other cities or related to other birth outcomes.

Assessment of regeneration in meniscal lesions by use of mesenchymal stem cells derived from equine bone marrow and adipose tissue.

OBJECTIVE To assess the ability to regenerate an equine meniscus by use of a collagen repair patch (scaffold) seeded with mesenchymal stem cells (MSCs) derived from bone marrow (BM) or adipose tissue (AT). SAMPLE 6 female Hispano-Breton horses between 4 and 7 years of age; MSCs from BM and AT were obtained for the in vitro experiment, and the horses were subsequently used for the in vivo experiment. PROCEDURES Similarities and differences between MSCs derived from BM or AT were investigated in vitro by use of cell culture. In vivo assessment involved use of a meniscus defect and implantation on a scaffold. Horses were allocated into 2 groups. In one group, defects in the medial meniscus were treated with MSCs derived from BM, whereas in the other group, defects were treated with MSCs derived from AT. Defects were created in the contralateral stifle joint but were not treated (control samples). RESULTS Both types of MSCs had universal stem cell characteristics. For in vivo testing, at 12 months after treatment, treated defects were regenerated with fibrocartilaginous tissue, whereas untreated defects were partially repaired or not repaired. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that MSCs derived from AT could be a good alternative to MSCs derived from BM for use in regenerative treatments. Results also were promising for a stem cell-based implant for use in regeneration in meniscal lesions. IMPACT FOR HUMAN MEDICINE Because of similarities in joint disease between horses and humans, these results could have applications in humans.

Ecotoxicity of sediments in rivers: Invertebrate community, toxicity bioassays and the toxic unit approach as complementary assessment tools.

The determination of the real toxicity of sediments in aquatic ecosystems is challenging and necessary for an appropriate risk assessment. Different approaches have been developed and applied over the last several decades. Currently, the joint implementation of chemical, ecological and toxicological tools is recommended for an appropriate and successful toxicity risk assessment. We chose the combination of the toxic unit approach with acute pore water tests (Vibrio fischeri, Pseudokirchneriella subcapitata and Daphnia magna) and whole-sediment exposure tests (V. fischeri, Chironomus riparius), together with invertebrate community composition (multivariate analyses) to detect short and long-term responses of the organisms in four rivers of the Iberian Peninsula. High toxicity was detected in three sites (the downstream sites of the Llobregat and the Júcar, and the most upstream site of the Ebro). We identified organophosphate insecticides and metals as the main variables responsible for this toxicity, particularly in the whole-sediment tests. In particular, chlorpyrifos was mostly responsible for the toxicity (TUs) of D. magna, coinciding with the C. riparius mortality (long-term toxicity) in the mentioned sites, and copper was the main pollutant responsible for the short-term toxicity of P. subcapitata. The combination of the different approaches allowed us to detect ecotoxicological effects in organisms and identify the main contributors to the toxicity in these multi-stressed rivers.

Desarrollo tecnológico de succinilcolina infantil 100 mg, inyectable en solución / Technological development of 100 mg infant succinylcoline, injectable in a solution

Objetivo: desarrollar una nueva formulación inyectable en solución acuosa de succinilcolina, para uso pediátrico. Métodos: se utiliza la materia prima cloruro de succinilcolina con demostrada calidad para el diseño de la formulación. Fueron ensayadas tres variantes de formulación, durante seis meses, a una temperatura de 25±2 oC y una humedad relativa de 60±5 por ciento, se analiza la influencia de los componentes y el envase sobre el contenido del fármaco. Resultados: la formulación envasada en bulbos 6R, sin agentes preservantes, se selecciona como la mejor variante. Los tres lotes a escala de laboratorio cumplieron con los parámetros de calidad establecidos y se realizó el escalado piloto. Conclusiones: se comprobó la factibilidad del desarrollo del inyectable en solución de succinilcolina infantil 100mg(AU)

Objective: to develop a new injectable formulation in aqueos solution of succinylcoline for pediatric uses. Methods: the raw material for the formulation was succinylcoline chloride with proven quality for this design. Three variants of formulation were tested for six months at a temperature of 25±2 oC and relative humidity of 60±5 percent. The influence of the components and of the packing on the contents of the drug was analyzed. Results: the formulation packed in flasks 6R with no preserving agent was chosen as the best. Three batches at lab scale met the set quality parameters and also a pilot scale-up was performed. Conclusions: the feasibility of the development of an injectable product in 100mg infant succinylcoline solution(AU)

The prevalence of sarcopenia in patients with respiratory failure classified as normally nourished using computed tomography and subjective global assessment.

BACKGROUND: Declines in nutrition status and adverse body composition changes frequently occur in the critically ill. The objective of this cross-sectional study was to examine the prevalence of sarcopenia and its occurrence in patients classified as normal nourished using subjective global assessment (SGA). METHODS: Exploiting diagnostic CT images, skeletal muscle mass at the L3 region was quantified and used to determine sarcopenia and its association with normal nutrition status in 56 patients with respiratory failure. Sarcopenia was defined as an L3 skeletal muscle index of ≤38.5 cm(2)/m(2) for women and ≤52.4 cm(2)/m(2) for men. CT imaging and SGA classifications completed within 14, 10 and 7 days of each other were analyzed to assess sarcopenia and the influence of time between scans on misclassification (ie, normal nourished and sarcopenic). Descriptive statistics were conducted. RESULTS: The average patient was 59.2 (± 15.6) years old, admitted with sepsis/infection, an APACHE II score of 26 (± 8.0), and BMI of 28.3 (± 5.8). Sarcopenia and sarcopenic obesity were prevalent in a minimum of 56% and 24% of patients, respectively, depending on the number of days between CT imaging and SGA assessment. Misclassified individuals were predominantly male, minority and overweight or obese. Controlling for age, no significant differences were noted for patients classified as normal nourished vs malnourished by SGA for lumbar muscle cross-sectional, whole-body lean mass, or skeletal muscle index. CONCLUSIONS: Sarcopenia is highly prevalent among patients with respiratory failure requiring mechanical ventilation (MV) and not readily detected in patients classified as normal nourished using SGA.