Dedifferentiation of leaf explants and antileukemia activity of an ethanolic extract of cell cultures of Moringa oleifera

The present study was aimed at developing an efficient protocol for callus induction from the leaves of Moringa oleifera and to investigate its crude extract antileukemia activity on leukemia cells. Several secondary metabolites are present in M. oleifera as the plant serves as reservoirs for various bioactive compounds. Callus cultures of M. oleifera were induced from leaf explants incubated on MS medium supplemented with different concentrations of 2,4-dichloro-phenoxyacetic acid (2,4-D). The crude extracts of the callus were evaluated in vitro for their activity against leukemia cells and hepatocarcinoma. Among the different concentrations, 2,4-D at 0.1 mg/l induced highest frequencies of callus growth index (7.8) when compared with other concentrations. Ethanolic extracts killed about 36% of abnormal cells among primary cells harvested from 3 patients with acute myeloid leukemia (AML) and hepatocarcinoma cells HpG2. These results provide an in vitro evidence and support the traditional use of M. oleifera leaf as a potent source of anticancer. However, more researches are needed at phytochemical and clinical levels to confirm the traditional use of this plant as anticancer.Keywords: Moinga olifera, callus culture, antileukemia, hepatocarcinom

Impairment and Restoration of Homeostatic Plasticity in Cultured Cortical Neurons From a Mouse Model of Huntington Disease

Huntington disease (HD) is an inherited neurodegenerative disorder caused by a mutation in the huntingtin gene. The onset of symptoms is preceded by synaptic dysfunction. Homeostatic synaptic plasticity (HSP) refers to processes that maintain the stability of networks of neurons, thought to be required to enable new learning and cognitive flexibility. One type of HSP is synaptic scaling, in which the strength of all of the synapses onto a cell increases or decreases following changes in the cell’s level of activity. Several pathways implicated in synaptic scaling are dysregulated in HD, including brain-derived neurotrophic factor (BDNF) and calcium signaling. Here, we investigated whether HSP is disrupted in cortical neurons from an HD mouse model. We treated cultured cortical neurons from wild-type (WT) FVB/N or YAC128 HD mice with tetrodotoxin (TTX) for 48 h to silence action potentials and then recorded miniature excitatory postsynaptic currents. In WT cultures, these increased in both amplitude and frequency after TTX treatment, and further experiments showed that this was a result of insertion of AMPA receptors and formation of new synapses, respectively. Manipulation of BDNF concentration in the culture medium revealed that BDNF signaling contributed to these changes. In contrast to WT cortical neurons, YAC128 cultures showed no response to action potential silencing. Strikingly, we were able to restore the TTX-induced changes in YAC128 cultures by treating them with pridopidine, a drug which enhances BDNF signaling through stimulation of the sigma-1 receptor (S1R), and with the S1R agonist 3-PPP. These data provide evidence for disruption of HSP in cortical neurons from an HD mouse model that is restored by stimulation of S1R. Our results suggest a potential new direction for developing therapy to mitigate cognitive deficits in HD

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

Active principle from Moringa oleifera Lam leaves effective against two leukemias and a hepatocarcinoma

Medicinal plants are important elements of indigenous medical system that have persisted in developing countries. Many of the pharmacological principles currently used as anticancer agents were first isolated from plants. However, some important anticancer agents are still extracted from plants because they cannot be synthesized chemically on a commercial scale due to their complex structures that often contain several chiral centers. The aim of this study was to test different extracts from the leaves of Moringa or drumstick tree (Moringa oleifera) for activity against leukemia and hepatocarcinoma cells in vitro. The extracts could kill majority (70 - 86%) of the abnormal cells among primary cells harvested from 10 patients with acute lymphoblastic leukemia (ALL) and 15 with acute myeloid leukemia (AML) as well as a culture of hepatocarcinoma cells (75% death), but most significantly by the hot water and ethanol extracts. In conclusion, M. oleifera may have potential for use as source of natural treatment for diseases such as cancer.Key words: Moringa oleifera, anti-cancer, acute lymphoblastic leukemia, acute myeloid leukemia, hepatocarcinoma

Auditory and language outcomes in children with unilateral hearing loss

Objectives: Children with unilateral hearing loss (UHL) are being diagnosed at younger ages because of newborn hearing screening. Historically, they have been considered at risk for difficulties in listening and language development. Little information is available on contemporary cohorts of children identified in the early months of life. We examined auditory and language acquisition outcomes in a contemporary cohort of early-identified children with UHL and compared their outcomes at preschool age with peers with mild bilateral loss and with normal hearing. Design: As part of the Mild and Unilateral Hearing Loss in Children Study, we collected auditory and spoken language outcomes on children with unilateral, bilateral hearing loss and with normal hearing over a four-year period. This report provides a cross-sectional analysis ofresults at age 48 months. A total of 120 children (38 unilateral and 31 bilateral mild, 51 normal hearing) were enrolled in the study from 2010-2015. Children started the study at varying ages between 12 and 36 months of age and were followed until age 36-48 months. The median age of identification of hearing loss was 3.4 months (IQR: 2.0, 5.5) for unilateral and 3.6 months (IQR: 2.7, 5.9) for the mild bilateral group. Families completed an intake form at enrolment to provide baseline child and family­ related characteristics. Data on amplification fitting and use were collected via parent questionnaires at each annual assessment interval. This study involved a range of auditory development and language measures. For this report, we focus on the end of follow-up results from two auditory development questionnaires and three standardized speech-language assessments. Assessments included in this report were completed at a median age of 47.8 months (IQR: 38.8, 48.5). Using ANOVA, we examined auditory and language outcomes in children with UHL and compared their scores to children with mild bilateral hearing loss and those with normal hearing. Results: On most measures, children with UHL performed poorer than those in the mild bilateral and normal hearing study groups. All children with hearing loss performed at lower levels compared to the normal hearing control group. However, mean standard scores for the normal hearing group in this study were above normative means for the language measures. In particular, children with UHL showed gaps compared to the normal hearing control group in functional auditory listening and in receptive and expressive language skills (three quarters of one standard deviation below) at age 48 months. Their performance in receptive vocabulary and speech production was not significantly different from that of their hearing peers (p<0.001). Conclusions: Even when identified in the first months oflife, children with UHL show a tendency to lag behind their normal hearing peers in functional auditory listening and in receptive and expressive language development

A multi-color quantum well photodetector for mid- and long-wavelength infrared detection

The authors report a two-color quantum well infrared photodetector at room temperature operating in the mid- and long-wavelength infrared detection. To this purpose, the band alignment is tailored and electronic properties are investigated for the proposed structure based on Ga1−xInxAsySb1−y/GaSb and AlxGa1−xAsySb1−y/GaSb. As accurate knowledge of band offsets is required in device modeling, we have proceeded to theoretical investigations of the band offsets for pseudo-morphically strained and lattice-matched Ga1−xInxAsySb1−y/GaSb and AlxGa1−xAsySb1−y/GaSb heterointerfaces in the whole range of alloy compositions 0 ≤ x, y ≤ 1. The carrier effective masses are deduced from the laws extracted from the k.p strain Hamiltonian laws. For the modeled heterostructure, the dark current of about 10−1 A cm−2 at ambient temperature shows the high performance of this multi-color infrared photodetector around 5 and 12.5 µm wavelengths