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The neuromuscular junction (NMJ) consists of three components, namely presynaptic motor neurons, postsynaptic muscle fibers and perisynaptic Schwann cells (PSCs). The role of Schwann cells (SCs) in regulating NMJ structural and functional development remains unclear. In this study, mice with conditional inactivation of neurofibromin 1 (Nf1) and phosphatase and tensin homolog (Pten), specifically in SCs, resulted in delayed NMJ maturation that led to delayed muscle growth, recapitulating the muscular dystrophy condition observed in human neurofibromatosis type I syndrome (NF1) patients. Expression levels of NMJ development related molecules such as cholinergic receptor, nicotinic, alpha polypeptide 1 (Chrna1), agrin (Agrn), dystrophin, muscular dystrophy (Dmd), laminin, beta 2 (Lamb2) and dystroglycan 1 (Dag1) were also downregulated. To further explore the molecular alterations in these SCs, NF1- and PTEN-related pathways were analyzed in mutant sciatic nerves. As expected, hyperactive RAS/PI3K/AKT/mTOR signaling pathways were identified, suggesting the importance of these pathways for NMJ development, and subsequent muscle maturation.

Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive form of soft tissue neoplasm with extremely poor prognosis and no effective medical options currently available. MPNSTs can occur either sporadically or in association with the neurofibromatosis type 1 (NF1) syndrome. Importantly, activation of RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, and WNT/CTNNB1 signaling pathways has been reported in both NF1‐related and late‐stage sporadic MPNSTs. In this study, we found that DAW22, a natural sesquiterpene coumarin compound isolated from Ferula ferulaeoides (Steud.) Korov., could inhibit cell proliferation and colony formation in five established human MPNST cancer cell lines. Further molecular mechanism exploration indicated that DAW22 could target the main components in the MPNST tumorigenic pathways: namely suppress phosphorylation of AKT and ERK, and reduce levels of non‐phospho (active) CTNNB1. Using the xenograft mouse model transplanted with human MPNST cancer cell line, daily treatment with DAW22 for 25 days was effective in reducing tumor growth. These results support DAW22 as an alternative therapeutic compound for MPNST treatment by affecting multiple signaling transduction pathways in its disease progression. In this study, we evaluated the anti‐tumor effect of natural compound DAW22 on malignant peripheral nerve sheath tumors (MPNSTs) using both in vitro and in vivo approaches. The anti‐tumor effect was caused by the induction of apoptosis and targeting of AKT, ERK, and CTNNB1 signaling pathways. These results support DAW22 as an alternative therapeutic compound for MPNST treatment by affecting multiple signaling transduction pathways in its disease progression.

Malignant peripheral nerve sheath tumors ( MPNST s) are an aggressive form of soft tissue neoplasm with extremely poor prognosis and no effective medical options currently available. MPNST s can occur either sporadically or in association with the neurofibromatosis type 1 ( NF 1) syndrome. Importantly, activation of RAS / RAF / MEK / ERK , PI 3K/ AKT / mTOR , and WNT / CTNNB 1 signaling pathways has been reported in both NF 1‐related and late‐stage sporadic MPNST s. In this study, we found that DAW 22, a natural sesquiterpene coumarin compound isolated from Ferula ferulaeoides (Steud.) Korov ., could inhibit cell proliferation and colony formation in five established human MPNST cancer cell lines. Further molecular mechanism exploration indicated that DAW 22 could target the main components in the MPNST tumorigenic pathways: namely suppress phosphorylation of AKT and ERK , and reduce levels of non‐phospho (active) CTNNB 1. Using the xenograft mouse model transplanted with human MPNST cancer cell line, daily treatment with DAW 22 for 25 days was effective in reducing tumor growth. These results support DAW 22 as an alternative therapeutic compound for MPNST treatment by affecting multiple signaling transduction pathways in its disease progression.

At homeostasis the vast majority of neutrophils in the circulation expresses CD16 and CD62L within a narrow expression range, but this quickly changes in disease. Little is known regarding the changes in kinetics of neutrophils phenotypes in inflammatory conditions. During acute inflammation more heterogeneity was found, characterized by an increase in CD16 dim banded neutrophils. These cells were probably released from the bone marrow (left shift). Acute inflammation induced by human experimental endotoxemia (LPS model) was additionally accompanied by an immediate increase in a CD62L low neutrophil population, which was not as explicit after injury/trauma induced acute inflammation. The situation in sub-acute inflammation was more complex. CD62L low neutrophils appeared in the peripheral blood several days (>3 days) after trauma with a peak after 10 days. A similar situation was found in the blood of COVID-19 patients returning from the ICU. Sorted CD16 low and CD62L low subsets from trauma and COVID-19 patients displayed the same nuclear characteristics as found after experimental endotoxemia. In diseases associated with chronic inflammation (stable COPD and treatment naive HIV) no increases in CD16 low or CD62L low neutrophils were found in the peripheral blood. All neutrophil subsets were present in the bone marrow during homeostasis. After LPS rechallenge, these subsets failed to appear in the circulation, but continued to be present in the bone marrow, suggesting the absence of recruitment signals. Because the subsets were reported to have different functionalities, these results on the kinetics of neutrophil subsets in a range of inflammatory conditions contribute to our understanding on the role of neutrophils in health and disease.

Sleep, both overnight and daytime naps, can facilitate the consolidation of declarative memories in healthy humans. However, it is unclear whether such beneficial effects of sleep occur in special populations, such as individuals with elevated neuropsychiatric symptoms, and if they apply to clinically relevant material that may have personal significance to those populations. We examined memory retention over a 60-minute interval of wakefulness or nap opportunity in participants with low or elevated scores (≤13 and ≥21, respectively) on the Beck Depression Inventory-II (BDI-II). Memory for depression-related information was assessed by (a) free-recall of a video depicting a personal experience narrative of the impact of depression on cognition and workplace performance; and (b) a paired-associates task linking depression-related cognitive symptoms to appropriate coping strategies. The results showed no overall difference in recall between the nap and waking condition. However, across the full sample of participants, there were significant positive correlations between total sleep time and paired associates recall, and slow wave sleep (SWS) percentage and story free recall performance. Unexpectedly, participants with elevated BDI-II scores exhibited better free-recall performance compared to those with low scores. These results suggest that sleep, specifically SWS, may stabilize memories for clinically relevant information in populations with low and elevated depressive symptoms. The superior recall in participants with elevated-BDI scores may be related to the personal significance and stronger encoding of depression-related information. These observations raise the possibility that mnemonic deficits in depressed patients may be, at least in part, related to the type of information used to assess memory performance.

To validate a locally developed chromatography-based method to monitor emerging drugs of abuse whilst performing regular drug testing in abusers. Cross-sectional study. Eleven regional hospitals, seven social service units, and a tertiary level clinical toxicology laboratory in Hong Kong. A total of 972 drug abusers and high-risk individuals were recruited from acute, rehabilitation, and high-risk settings between 1 November 2011 and 31 July 2013. A subset of the participants was of South Asian ethnicity. In total, 2000 urine or hair specimens were collected. Proof of concept that surveillance of emerging drugs of abuse can be performed whilst conducting routine drug of abuse testing in patients. The method was successfully applied to 2000 samples with three emerging drugs of abuse detected in five samples: PMMA (paramethoxymethamphetamine), TFMPP [1-(3-trifluoromethylphenyl)piperazine], and methcathinone. The method also detected conventional drugs of abuse, with codeine, methadone, heroin, methamphetamine, and ketamine being the most frequently detected drugs. Other findings included the observation that South Asians had significantly higher rates of using opiates such as heroin, methadone, and codeine; and that ketamine and cocaine had significantly higher detection rates in acute subjects compared with the rehabilitation population. This locally developed analytical method is a valid tool for simultaneous surveillance of emerging drugs of abuse and routine drug monitoring of patients at minimal additional cost and effort. Continued, proactive surveillance and early identification of emerging drugs will facilitate prompt clinical, social, and legislative management.

Fil: Kaminsky, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución; Argentina

Pollen grains of Commelinaceae and Pontederiaceae (Commelinales) from the Río de La Plata wetlands (Argentina). The characters of pollen grains of the Commelinaceae and Pontederiaceae growing in the Río de la Plata wetlands were studied. Analyses were performed with light and scanning electron microscope. An update of some previously known data was made, and pollen of Pontederia rotundifolia and Tradescantia cerinthoides is described here for the first time. Both families have heteropolar pollen grains with bilateral symmetry. Commelinaceae bear monosulcate, and echinate sporoderm, while disulcate, smooth, verrucose or fossulate sporoderm, were found in Pontederiaceae. Fossulate type of exine is new to the family. Membrane of the sulci is usually present, with absent or barely present exine, represented by a thin layer of nexine. Ornamentation varies in different taxonomic levels: allows distinction among of tribes and genera of the studied Commelinaceae, and is a species trait in the Pontederiaceae from the area. Polen de Commelinaceae y Pontederiaceae (Commelinales) de humedales rioplatenses (Argentina). Se estudiaron los caracteres de los granos de polen de Commelinaceae y Pontederiaceae que crecen en áreas de humedales rioplatenses. Los estudios se realizaron con microscopio óptico y electrónico de barrido. Se actualizaron los conocimientos previos sobre elementos de esos grupos, y se describió por primera vez el polen de Pontederia rotundifolia y Tradescantia cerinthoides. Los granos de polen de ambas familias son heteropolares y tienen simetría bilateral. Son monosulcados, equinados en Commelinaceae, y disulcados, con esporodermis lisa, verrugosa o fosulada en Pontederiaceae, este último tipo, nuevo para la familia. La mayoría de los granos presentan membrana del sulco con exina ausente o presente como una delgada capa de nexina. La ornamentación varía en diferentes niveles jerárquicos: permite distinguir tribus y géneros de Commelinaceae, mientras que es un carácter específico en las Pontederiaceae del área.

Polen de Commelinaceae y Pontederiaceae (Commelinales) de humedales rioplatenses (Argentina). Se estudiaron los caracteres de los granos de polen de Commelinaceae y Pontederiaceae que crecen en áreas de humedales rioplatenses. Los estudios se realizaron con microscopio óptico y electrónico de barrido. Se actualizaron los conocimientos previos sobre elementos de esos grupos, y se describió por primera vez el polen de Pontederia rotundifolia y Tradescantia cerinthoides. Los granos de polen de ambas familias son heteropolares y tienen simetría bilateral. Son monosulcados, equinados en Commelinaceae, y disulcados, con esporodermis lisa, verrugosa o fosulada en Pontederiaceae, este último tipo, nuevo para la familia. La mayoría de los granos presentan membrana del sulco con exina ausente o presente como una delgada capa de nexina. La ornamentación varía en diferentes niveles jerárquicos: permite distinguir tribus y géneros de Commelinaceae, mientras que es un carácter específico en las Pontederiaceae del área.

El dengue es una infección transmitida por mosquitos que se presenta en todas las regiones tropicales y subtropicales del planeta. En años recientes, la transmisión ha aumentado de manera predominante en zonas urbanas y semiurbanas y se ha convertido en un importante problema de salud pública. El Instituto Nacional de Salud-INS, ubicó a Cali como el municipio con más casos de dengue en Colombia. De acuerdo con el INS, en la ciudad de Cali, hasta la semana epidemiológica 18 (del 28 de abril al 4 de mayo de 2013), se han notificado 5 134 casos de dengue y 171 de dengue grave. En este trabajo se presenta la descripción del modelo Ross McDonald, el análisis cualitativo de dicho modelo, y el análisis de sensibilidad del modelo a cambios en sus parámetros. Y base en el ajuste del modelo obtenido para los casos presentados en el 2010, se hacen y analizan simulaciones de posibles escenarios de brotes epidémicos en la ciudad de Cali. Palabras Clave: Dengue, modelos matemáticos, análisis cualitativo, simulación por computador (fuente: DeCS, BIREME). Dengue is an infection transmitted by mosquitoes and is present in all tropical and subtropical regions of the planet. In recent years, the transmission of the disease has increased, predominantly in urban and semi-urban areas, and has become an important public health problem. The National Health Institute (Instituto Nacional de Salud-INS) determined Cali to be the municipality with the most cases of dengue in Colombia. According to the INS, up to epidemiological week 18 (April 28 to May 4, 2013) 5 134 cases of dengue--and 171 cases of severe dengue--have been reported. This study presents a description of the Ross-Macdonald model, and qualitative analysis of this model, and an analysis of the sensitivity of the model to changes in its parameters. Based on the adjustment of the model obtained for cases that occurred in 2010, simulations of possible scenarios of epidemic outbreaks in the city of Cali are created and analyzed. Key Words: Dengue, mathematical models, qualitative analysis, computer simulation (source: MeSH, NLM).