Outwelling of nutrients into the Pasur River estuary from the Sundarbans mangrove creeks.

The Pasur River estuary (PRE), the largest estuary in the Sundarbans mangrove area, provides vital fishery resources and supports millions of livelihoods in the southwestern coastal region of Bangladesh. This study focused on the tidal and run-off effects on the outwelling of nutrients from the Sundarbans mangrove creeks to the PRE. Spatial and temporal variations of nutrient and chlorophyll-a concentrations were assessed by water sampling at 11 stations in the study area from January to December 2019. Dissolved inorganic nutrients and chlorophyll-a were analyzed by standard methods using a spectrophotometer. In the tidal mangrove creeks, dissolved inorganic nitrogen, phosphate, and silica concentrations were significantly higher (p < 0.05) during the spring tide than those during the neap tide, suggesting that these nutrients were flushed from the mangrove area by the inundation and tidal mixing of the spring tide. In general, chlorophyll-a (mean ± SD) concentrations in the PRE and the tidal mangrove creeks were 5.62 ± 1.30 µg/L and 9.03 ± 0.59 µg/L in the wet season, respectively. During the dry season, the chlorophyll-a decreased to 4.37 µg/L ± 0.68 and 4.94 ± 1.52 µg/L in the PRE and the tidal mangrove creek, respectively. The amount of nutrients outwelled from the mangrove creeks to the estuary was 1.53 ± 0.67 mg/L DIP, 0.001 ± 0.0004 mg/L DIN, and 1.38 ± 0.48 mg/L dissolved silica. DIP, silica, and chlorophyll-a concentrations were significantly higher (p < 0.05) during the spring tide compared to the neap tide, but salinity was not significantly (p > 0.05) different between the two tidal levels. This study showed that the mangrove creeks formed an important link in transporting nutrients from the mangrove forest to the estuary.

Dominant phytoplankton groups as the major source of polyunsaturated fatty acids for hilsa (Tenualosa ilisha) in the Meghna estuary Bangladesh.

The tropical estuarine ecosystem is fascinating for studying the dynamics of water quality and phytoplankton diversity due to its frequently changing hydrological conditions. Most importantly, phytoplankton is the main supplier of ω3 polyunsaturated fatty acids (PUFA) in the coastal food web for fish as they could not synthesize PUFA. This study evaluated seasonal variations of water quality parameters in the Meghna River estuary (MRE), explored how phytoplankton diversity changes according to hydro-chemical parameters, and identified the major phytoplankton groups as the main source of PUFA for hilsa fish. Ten water quality indicators including temperature, dissolved oxygen, pH, salinity, dissolved inorganic nitrogen (DIN = nitrate, nitrite, ammonia) and phosphorus, dissolved silica and chlorophyll-a were evaluated. In addition, phytoplankton diversity was assessed in the water and hilsa fish gut. Principal component analysis (PCA) was used to analyze the spatio-temporal changes in the water quality conditions, and the driving factors in the MRE. Four main components were extracted and explained 75.4% variability of water quality parameters. The most relevant driving factors were dissolved oxygen, salinity, temperature, and DIN (nitrate, nitrite and ammonia). These variabilities in physicochemical parameters and dissolved inorganic nutrients caused seasonal variations in two major groups of phytoplankton. Peak abundance of Chlorophyta (green algae) occurred in water in nutrient-rich environments (nitrogen and phosphorus) during the wet (36%) season, while Bacillariophyta (diatoms) were dominant during the dry (32%) season that depleted dissolved silica. Thus, the decrease of green algae and the increase of diatoms in the dry season indicated the potential link to seasonal changes of hydro-chemical parameters. The green algae (53.7%) were the dominant phytoplankton group in the hilsa gut content followed by diatoms (22.6%) and both are contributing as the major source of PUFAs for hilsa fish according to the electivity index as they contain the highest amounts of PUFAs (60 and 28% respectively).

Process analysis of pluripotent stem cell differentiation to megakaryocytes to make platelets applying European GMP.

Quality, traceability and reproducibility are crucial factors in the reliable manufacture of cellular therapeutics, as part of the overall framework of Good Manufacturing Practice (GMP). As more and more cellular therapeutics progress towards the clinic and research protocols are adapted to comply with GMP standards, guidelines for safe and efficient adaptation have become increasingly relevant. In this paper, we describe the process analysis of megakaryocyte manufacture from induced pluripotent stem cells with a view to manufacturing in vitro platelets to European GMP for transfusion. This process analysis has allowed us an overview of the entire manufacturing process, enabling us to pinpoint the cause and severity of critical risks. Risk mitigations were then proposed for each risk, designed to be GMP compliant. These mitigations will be key in advancing this iPS-derived therapy towards the clinic and have broad applicability to other iPS-derived cellular therapeutics, many of which are currently advancing towards GMP-compliance. Taking these factors into account during protocol design could potentially save time and money, expediting the advent of safe, novel therapeutics from stem cells.

Nutritional status and disease severity in children acutely presenting to a primary health clinic in rural Gambia.

BACKGROUND: Accurate and timely data on the health of a population are key for evidence-based decision making at both the policy and programmatic level. In many low-income settings, such data are unavailable or outdated. Using an electronic medical records system, we determined the association between nutritional status and severe illness and mortality among young children presenting to a rural primary health care facility in the Gambia. METHODS: Clinical data collected over five years (2010-2014) on children aged under 60 months making acute visits to a primary health care clinic in the rural Gambian district of Kiang West were retrospectively extracted from the medical records system. Generalised estimating equation models were used to investigate associations between nutritional status and illness severity, accounting for repeat visits, gender, age and access to transport to the clinic. The Population Attributable Fraction (PAF) was used to determine the proportion of severe illness likely attributable to different grades of malnutrition. RESULTS: 3839/5021 (77%) children under 60 months of age living in Kiang West presented acutely to the clinic at least once, yielding 21,278 visits (47% girls, median age 20.2 months (Interquartile Range (IQR) 23.92 months)) and 26,001 diagnoses, 86% being infectious diseases. Severe illness was seen in 4.5% of visits (961/21,278). Wasting was associated with an increased risk of severe illness in a dose-dependent manner, ('WHZ < -1' adjusted Odds Ratio (aOR) 1.68, 95% CI:1.43-1.98, p < 0.001, 'WHZ <-2 and ≥-3' aOR 2.78, 95% CI:2.31-3.36, p < 0.001 and 'WHZ < -3' aOR 7.82, 95% CI:6.40-9.55, p < 0.001) the PAF for wasting (WHZ < -2) was 0.21 (95% CI: 0.18-0.24). Stunting, even in the most severe form (HAZ < -3), was not significantly associated with severe illness (aOR 1.19 95% CI:0.94-1.51) but was associated with a significantly increased risk of death (aOR 6.04 95% CI:1.94-18.78). CONCLUSION: In this population-based cohort of young children in rural Gambia, wasting was associated with disease severity in a dose-dependent manner. Further research is needed into strategies to identify and reach these children with effective interventions to improve their nutritional status.

Impact of fortified versus unfortified lipid-based supplements on morbidity and nutritional status: A randomised double-blind placebo-controlled trial in ill Gambian children.

BACKGROUND: Multiple micronutrients (MMN) are commonly prescribed in pediatric primary healthcare in sub-Saharan Africa to improve nutritional status and appetite without evidence for their effectiveness or international clinical guidelines. Community-wide MMN supplementation has shown limited and heterogeneous impact on growth and morbidity. Short-term ready-to-use therapeutic foods in acutely sick children in a hospital setting also had limited efficacy regarding subsequent growth. The effectiveness of MMN in improving morbidity or growth in sick children presenting for primary care has not been assessed. METHODS AND FINDINGS: We undertook a double-blind randomised controlled trial of small-quantity lipid-based nutrient supplements (SQ-LNS) fortified with 23 micronutrients in children aged 6 months (mo) to 5 years (y) presenting with an illness at a rural primary healthcare centre in The Gambia. Primary outcomes were repeat clinic presentations and growth over 24 wk. Participants were randomly assigned to receive 1 of 3 interventions: (1) supplementation with micronutrient-fortified SQ-LNS for 12 wk (MMN-12), (2) supplementation with micronutrient-fortified SQ-LNS for 6 wk followed by unfortified SQ-LNS for 6 wk (MMN-6), or (3) supplementation with unfortified SQ-LNS for 12 wk (MMN-0) to be consumed in daily portions. Treatment masking used 16 letters per 6-wk block in the randomisation process. Blinded intention-to-treat analysis based on a prespecified statistical analysis plan included all participants eligible and correctly enrolled. Between December 2009 and June 2011, 1,101 children (age 6-60 mo, mean 25.5 mo) were enrolled, and 1,085 were assessed (MMN-0 = 361, MMN-6 = 362, MMN-12 = 362). MMN supplementation was associated with a small increase in height-for-age z-scores 24 wk after recruitment (effect size for MMN groups combined: 0.084 SD/24 wk, 95% CI: 0.005, 0.168; p = 0.037; equivalent to 2-5 mm depending on age). No significant difference in frequency of morbidity measured by the number of visits to the clinic within 24 wk follow-up was detected with 0.09 presentations per wk for all groups (MMN-0 versus MMN-6: adjusted incidence rate ratio [IRR] 1.03, 95% CI: 0.92, 1.16; MMN-0 versus MMN-12: 1.05, 95% CI: 0.93, 1.18). In post hoc analysis, clinic visits significantly increased by 43% over the first 3 wk of fortified versus unfortified SQ-LNS (adjusted IRR 1.43; 95% CI: 1.07, 1.92; p = 0.016), with respiratory presentations increasing by 52% with fortified SQ-LNS (adjusted IRR 1.52; 95% CI: 1.01, 2.30; p = 0.046). The number of severe adverse events during supplementation were similar between groups (MMN-0 = 20 [1 death]; MMN-6 = 21 [1 death]; MMN-12 = 20 [0 death]). No participant withdrew due to adverse effects. Study limitations included the lack of supervision of daily supplementation. CONCLUSION: Prescribing micronutrient-fortified SQ-LNS to ill children presenting for primary care in rural Gambia had a very small effect on linear growth and did not reduce morbidity compared to unfortified SQ-LNS. An early increase in repeat visits indicates a need for the establishment of evidence-based guidelines and caution with systematic prescribing of MMN. Future research should be directed at understanding the mechanisms behind the lack of effect of MMN supplementation on morbidity measures and limited effect on growth. TRIAL REGISTRATION: ISRCTN 73571031.

Current strategies in meniscal regeneration.

The meniscus plays an important role in the biomechanics and tribology of the knee joint. Damage to or disease of the meniscus is now recognized to predispose to the development of osteoarthritis. Treatment of meniscal injury through arthroscopic surgery has become one of the most common orthopedic surgical procedures, and in the United States this can represent 10 to 20% of procedures related to the knee. The meniscus has a limited healing capacity constrained to the vascularized periphery and therefore, surgical repair of the avascular regions is not always feasible. Replacement and repair of the meniscus to treat injuries is being investigated using tissue engineering strategies. Promising as these approaches may be, there are, however, major barriers to overcome before translation to the clinic.