A review on the integrated agro-technology of papaya fruit

The aim of this review was first to explore the effect of different pre-harvest factors affecting the quality of papaya including genetic factors, climatic conditions, cultural practices on post-harvest quality of the papaya fruit. Post-harvest physiology of papaya in terms of its respiration, ethylene production and sensitivity and transpiration was reviewed. Post-harvest handling and factors affecting quality of papaya were also examined. Post-harvest biochemistry of papaya including enzyme activity, carbohydrates, organic acids, pigments and volatiles in papaya fruit were assessed. A review on post-harvest handling of papaya fruit including packaging and storage environments (temperature and relative humidity) were presented. On the other hand, the post-harvest microbiology of papaya was reviewed. Papaya supply chain is much limited to local destinations with quite few exceptions mainly due to lack of integrated post-harvest handling technologies. Pre- and post-harvest treatments were found to have a significant effect on post-harvest quality of papaya and the fruit storage stability under dry and hot climatic conditions of Africa. An integrated agro-technology research and development approach aimed at improved yield and quality at harvest as well as the maintenance of qualities of papaya fruit in order to encourage farmers to produce and for marketing of the papaya fruit under African local supply chain conditions and for export market is recommended.Key words: Papaya fruit, post-harvest, agro-technology, pre-harvest

Correlation between post-procedure residual thrombus and clinical outcome in deep vein thrombosis patients receiving pharmacomechanical thrombolysis in a multicenter randomized trial

PURPOSE: To evaluate relationships between immediate venographic results and clinical outcomes of pharmacomechanical catheter-directed venous thrombolysis (PCDT). MATERIALS AND METHODS: Venograms from 317 acute proximal DVT patients who received PCDT in a multicenter randomized trial were reviewed. Quantitative thrombus resolution was assessed by independent readers using a modified Marder scale. The physician operators recorded their visual assessments of thrombus regression and venous flow. These immediate post-procedure results were correlated with patient outcomes at 1, 12, and 24 months. RESULTS: PCDT produced substantial thrombus removal (p < 0.001 for pre-PCDT versus post-PCDT thrombus scores in all segments). At procedure end, spontaneous venous flow was present in 99% of iliofemoral venous segments and in 89% of femoral-popliteal venous segments. For the overall proximal DVT population, and for the femoral-popliteal DVT subgroup, post-PCDT thrombus volume did not correlate with 1-month or 24-month outcomes. For the iliofemoral DVT subgroup, over 1 and 24 months, symptom severity scores were higher (worse) and venous disease-specific quality of life (QOL) scores were lower (worse) in patients with greater post-PCDT thrombus volume, with the difference reaching statistical significance for the 24-month Villalta PTS severity (p=0.0098). Post-PCDT thrombus volume did not correlate with 12-month valvular reflux. CONCLUSION: PCDT successfully removes thrombus in acute proximal DVT. However, the residual thrombus burden at procedure end does not correlate with the occurrence of PTS during the subsequent 24 months. In iliofemoral DVT, lower residual thrombus burden correlates with reduced PTS severity and possibly also with improved venous QOL and fewer early symptoms

State-Dependent Accessibility of the P-S6 Linker of Pacemaker (HCN) Channels Supports a Dynamic Pore-to-Gate Coupling Model

The hyperpolarization-activated cyclic nucleotide-modulated channel gene family (HCN1-4) encodes the membrane depolarizing current that underlies pacemaking. Although the topology of HCN resembles Kv channels, much less is known about their structure-function correlation. Previously, we identified several pore residues in the S5-P linker and P-loop that are externally accessible and/or influence HCN gating, and proposed an evolutionarily conserved pore-to-gate mechanism. Here we sought dynamic evidence by assessing the functional consequences of Cys-scanning substitutions in the unexplored P-S6 linker (residues 352–359), the HCN1-R background (that is, resistant to sulfhydryl-reactive agents). None of A352C, Q353C, A354C, P355C, V356C, S357C, M358C, or S359C produced functional currents; the loss-of-function of Q353C, A354C, S357C, and M358C could be rescued by the reducing agent dithiothreitol. Q353C, A354C, and S357C, but not M358C and HCN1-R, were sensitive to Cd2+ blockade (IC50 = 3–12 μM vs. >1 mM). External application of the positively charged covalent sulfhydryl modifier MTSET irreversibly reduced I−140mV of Q353C and A354C to 27.9 ± 3.4% and 58.2 ± 13.1% of the control, respectively, and caused significant steady-state activation shifts (∆V1/2 = –21.1 ± 1.6 for Q353C and −10.0 ± 2.9 mV for A354C). Interestingly, MTSET reactivity was also state dependent. MTSET, however, affected neither S357C nor M358C, indicating site specificity. Collectively, we have identified novel P-S6 residues whose extracellular accessibility was sterically and state dependent and have provided the first functional evidence consistent with a dynamic HCN pore-to-gate model

Probing the bradycardic drug binding receptor of HCN-encoded pacemaker channels

If (or Ih), encoded by the hyperpolarization-activated, cyclic nucleotide-gated (HCN1–4) channel gene family, contributes significantly to cardiac pacing. Bradycardic agents such as ZD7288 that target HCN channels have been developed, but the molecular configuration of their receptor is poorly defined. Here, we probed the drug receptor by systematically introducing alanine scanning substitutions into the selectivity filter (C347A, I348A, G349A, Y350A, G351A in the P-loop), outer (P355A, V356A, S357A, M358A in the P-S6 linker), and inner (M377A, F378A, V379A in S6) pore vestibules of HCN1 channels. When heterologously expressed in human embryonic kidney 293 cells for patch-clamp recordings, I348A, G349A, Y350A, G351A, P355A, and V356A did not produce measurable currents. The half-blocking concentration (IC50) of wild type (WT) for ZD7288 was 25.8 ± 9.7 μM. While the IC50 of M358A was identical to WT, those of C347A, S357A, F378A, and V379A markedly increased to 137.6 ± 56.4, 113.3 ± 34.1, 587.1 ± 167.5, and 1726.3 ± 673.4 μM, respectively (p < 0.05). Despite the proximity of the S6 residues studied, M377A was hypersensitive (IC50 = 5.1 ± 0.7 μM; p < 0.05) implicating site specificity. To explore the energetic interactions among the S6 residues, double and triple substitutions (M377A/F378A, M377A/V379A, F378A/V379A, and M377A/F378A/V379A) were generated for thermodynamic cycle analysis. Specific interactions with coupling energies (ΔΔG) >1 kT for M377–F378 and F378–V379 but not M377–V379 were identified. Based on these new data and others, we proposed a refined drug-blocking model that may lead to improved antiarrhythmics and bioartificial pacemaker designs

Large-bore Mechanical Thrombectomy Versus Catheter-directed Thrombolysis in the Management of Intermediate-risk Pulmonary Embolism: Primary Results of the PEERLESS Randomized Controlled Trial.

BACKGROUND: There is a lack of randomized controlled trial (RCT) data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism (PE). METHODS: PEERLESS is a prospective, multicenter, RCT that enrolled 550 intermediate-risk PE patients with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with large-bore mechanical thrombectomy (LBMT) or catheter-directed thrombolysis (CDT). The primary endpoint was a hierarchal win ratio (WR) composite of the following: 1) all-cause mortality, 2) intracranial hemorrhage, 3) major bleeding, 4) clinical deterioration and/or escalation to bailout, and 5) postprocedural intensive care unit (ICU) admission and length of stay, assessed at the sooner of hospital discharge or 7 days post-procedure. Assessments at the 24-hour visit included respiratory rate, mMRC dyspnea score, NYHA classification, right ventricle (RV)/left ventricle (LV) ratio reduction, and RV function. Endpoints through 30 days included total hospital stay, all-cause readmission, and all-cause mortality. RESULTS: The primary endpoint occurred significantly less frequently with LBMT vs CDT (WR 5.01 [95% CI: 3.68-6.97]; P&lt;0.001). There were significantly fewer episodes of clinical deterioration and/or bailout (1.8% vs 5.4%; P=0.04) with LBMT vs CDT and less postprocedural ICU utilization (P&lt;0.001), including admissions (41.6% vs 98.6%) and stays &gt;24 hours (19.3% vs 64.5%). There was no significant difference in mortality, intracranial hemorrhage, or major bleeding between strategies, nor in a secondary WR endpoint including the first 4 components (WR 1.34 [95% CI: 0.78-2.35]; P=0.30). At the 24-hour visit, respiratory rate was lower for LBMT patients (18.3±3.3 vs 20.1±5.1; P&lt;0.001) and fewer had moderate to severe mMRC dyspnea scores (13.5% vs 26.4%; P&lt;0.001), NYHA classifications (16.3% vs 27.4%; P=0.002), and RV dysfunction (42.1% vs 57.9%; P=0.004). RV/LV ratio reduction was similar (0.32±0.24 vs 0.30±0.26; P=0.55). LBMT patients had shorter total hospital stays (4.5±2.8 vs 5.3±3.9 overnights; P=0.002) and fewer all-cause readmissions (3.2% vs 7.9%; P=0.03), while 30-day mortality was similar (0.4% vs 0.8%; P=0.62). CONCLUSIONS: PEERLESS met its primary endpoint in favor of LBMT vs CDT in treatment of intermediate-risk PE. LBMT had lower rates of clinical deterioration and/or bailout and postprocedural ICU utilization compared with CDT, with no difference in mortality or bleeding

The overlapping burden of the three leading causes of disability and death in sub-Saharan African children

Despite substantial declines since 2000, lower respiratory infections (LRIs), diarrhoeal diseases, and malaria remain among the leading causes of nonfatal and fatal disease burden for children under 5 years of age (under 5), primarily in sub-Saharan Africa (SSA). The spatial burden of each of these diseases has been estimated subnationally across SSA, yet no prior analyses have examined the pattern of their combined burden. Here we synthesise subnational estimates of the burden of LRIs, diarrhoea, and malaria in children under-5 from 2000 to 2017 for 43 sub-Saharan countries. Some units faced a relatively equal burden from each of the three diseases, while others had one or two dominant sources of unit-level burden, with no consistent pattern geographically across the entire subcontinent. Using a subnational counterfactual analysis, we show that nearly 300 million DALYs could have been averted since 2000 by raising all units to their national average. Our findings are directly relevant for decision-makers in determining which and targeting where the most appropriate interventions are for increasing child survival

The overlapping burden of the three leading causes of disability and death in sub-Saharan African children

Despite substantial declines since 2000, lower respiratory infections (LRIs), diarrhoeal diseases, and malaria remain among the leading causes of nonfatal and fatal disease burden for children under 5 years of age (under 5), primarily in sub-Saharan Africa (SSA). The spatial burden of each of these diseases has been estimated subnationally across SSA, yet no prior analyses have examined the pattern of their combined burden. Here we synthesise subnational estimates of the burden of LRIs, diarrhoea, and malaria in children under-5 from 2000 to 2017 for 43 sub-Saharan countries. Some units faced a relatively equal burden from each of the three diseases, while others had one or two dominant sources of unit-level burden, with no consistent pattern geographically across the entire subcontinent. Using a subnational counterfactual analysis, we show that nearly 300 million DALYs could have been averted since 2000 by raising all units to their national average. Our findings are directly relevant for decision-makers in determining which and targeting where the most appropriate interventions are for increasing child survival

Mapping inequalities in exclusive breastfeeding in low- and middle-income countries, 2000–2018

Abstract: Exclusive breastfeeding (EBF)—giving infants only breast-milk for the first 6 months of life—is a component of optimal breastfeeding practices effective in preventing child morbidity and mortality. EBF practices are known to vary by population and comparable subnational estimates of prevalence and progress across low- and middle-income countries (LMICs) are required for planning policy and interventions. Here we present a geospatial analysis of EBF prevalence estimates from 2000 to 2018 across 94 LMICs mapped to policy-relevant administrative units (for example, districts), quantify subnational inequalities and their changes over time, and estimate probabilities of meeting the World Health Organization’s Global Nutrition Target (WHO GNT) of ≥70% EBF prevalence by 2030. While six LMICs are projected to meet the WHO GNT of ≥70% EBF prevalence at a national scale, only three are predicted to meet the target in all their district-level units by 2030

The overlapping burden of the three leading causes of disability and death in sub-Saharan African children

Despite substantial declines since 2000, lower respiratory infections (LRIs), diarrhoeal diseases, and malaria remain among the leading causes of nonfatal and fatal disease burden for children under 5 years of age (under 5), primarily in sub-Saharan Africa (SSA). The spatial burden of each of these diseases has been estimated subnationally across SSA, yet no prior analyses have examined the pattern of their combined burden. Here we synthesise subnational estimates of the burden of LRIs, diarrhoea, and malaria in children under-5 from 2000 to 2017 for 43 sub-Saharan countries. Some units faced a relatively equal burden from each of the three diseases, while others had one or two dominant sources of unit-level burden, with no consistent pattern geographically across the entire subcontinent. Using a subnational counterfactual analysis, we show that nearly 300 million DALYs could have been averted since 2000 by raising all units to their national average. Our findings are directly relevant for decision-makers in determining which and targeting where the most appropriate interventions are for increasing child survival. © 2022, The Author(s).Funding text 1: This work was primarily supported by grant OPP1132415 from the Bill & Melinda Gates Foundation. ; Funding text 2: This study was funded by the Bill & Melinda Gates Foundation. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. The non-consortium authors have no competing interests . Competing interests for consortium authors is as follows: Robert Ancuceanu reports receiving consultancy or speaker feeds from UCB, Sandoz, Abbvie, Zentiva, Teva, Laropharm, CEGEDIM, Angelini, Biessen Pharma, Hofigal, AstraZeneca, and Stada. Jacek Jerzy Jozwiak reports personal fees from Amgen, ALAB Laboratories, Teva, Synexus, Boehringer Ingelheim, and Zentiva, all outside the submitted work. Kewal Krishan reports non-financial support from UGC Centre of Advanced Study, CAS II, Department of Anthropology, Panjab University, Chandigarh, India, outside the submitted work. Walter Mendoza is a Program Analyst in Population and Development at the United Nations Population Fund-UNFPA Country Office in Peru, which does not necessarily endorse or support these findings. Maarten J Postma reports grants and personal fees from MSD, GSK, Pfizer, Boehringer Ingelheim, Novavax, BMS, Seqirus, Astra Zeneca, Sanofi, IQVIA, grants from Bayer, BioMerieux, WHO, EU, FIND, Antilope, DIKTI, LPDP, Budi, personal fees from Novartis, Quintiles, Pharmerit, owning stock options in Health-Ecore and PAG Ltd, and being advisor to Asc Academics, all outside the submitted work. Jasviner A Singh reports personal fees from Crealta/Horizon, Medisys, Fidia, UBM LLC, Trio health, Medscape, WebMD, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, Practice Point communications, the National Institutes of Health, the American College of Rheumatology, and Simply Speaking, owning stock options in Amarin, Viking, Moderna, Vaxart pharmaceuticals and Charlotte’s Web Holdings, being a member of FDA Arthritis Advisory Committee, the steering committee of OMERACT, an international organization that develops measures for clinical trials and receives arm’s length funding from 12 pharmaceutical companies, and the Veterans Affairs Rheumatology Field Advisory Committee, and acting as Editor and Director of the UAB Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis, all outside the submitted work. Era Upadhyay has a patent A system and method of reusable filters for anti-pollution mask pending, and a patent A system and method for electricity generation through crop stubble by using microbial fuel cells pending

Global, regional, and national mortality among young people aged 10–24 years, 1950–2019: a systematic analysis for the Global Burden of Disease Study 2019

Summary: Background Documentation of patterns and long-term trends in mortality in young people, which reflect huge changes in demographic and social determinants of adolescent health, enables identification of global investment priorities for this age group. We aimed to analyse data on the number of deaths, years of life lost, and mortality rates by sex and age group in people aged 10–24 years in 204 countries and territories from 1950 to 2019 by use of estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods We report trends in estimated total numbers of deaths and mortality rate per 100 000 population in young people aged 10–24 years by age group (10–14 years, 15–19 years, and 20–24 years) and sex in 204 countries and territories between 1950 and 2019 for all causes, and between 1980 and 2019 by cause of death. We analyse variation in outcomes by region, age group, and sex, and compare annual rate of change in mortality in young people aged 10–24 years with that in children aged 0–9 years from 1990 to 2019. We then analyse the association between mortality in people aged 10–24 years and socioeconomic development using the GBD Socio-demographic Index (SDI), a composite measure based on average national educational attainment in people older than 15 years, total fertility rate in people younger than 25 years, and income per capita. We assess the association between SDI and all-cause mortality in 2019, and analyse the ratio of observed to expected mortality by SDI using the most recent available data release (2017). Findings In 2019 there were 1·49 million deaths (95% uncertainty interval 1·39–1·59) worldwide in people aged 10–24 years, of which 61% occurred in males. 32·7% of all adolescent deaths were due to transport injuries, unintentional injuries, or interpersonal violence and conflict; 32·1% were due to communicable, nutritional, or maternal causes; 27·0% were due to non-communicable diseases; and 8·2% were due to self-harm. Since 1950, deaths in this age group decreased by 30·0% in females and 15·3% in males, and sex-based differences in mortality rate have widened in most regions of the world. Geographical variation has also increased, particularly in people aged 10–14 years. Since 1980, communicable and maternal causes of death have decreased sharply as a proportion of total deaths in most GBD super-regions, but remain some of the most common causes in sub-Saharan Africa and south Asia, where more than half of all adolescent deaths occur. Annual percentage decrease in all-cause mortality rate since 1990 in adolescents aged 15–19 years was 1·3% in males and 1·6% in females, almost half that of males aged 1–4 years (2·4%), and around a third less than in females aged 1–4 years (2·5%). The proportion of global deaths in people aged 0–24 years that occurred in people aged 10–24 years more than doubled between 1950 and 2019, from 9·5% to 21·6%. Interpretation Variation in adolescent mortality between countries and by sex is widening, driven by poor progress in reducing deaths in males and older adolescents. Improving global adolescent mortality will require action to address the specific vulnerabilities of this age group, which are being overlooked. Furthermore, indirect effects of the COVID-19 pandemic are likely to jeopardise efforts to improve health outcomes including mortality in young people aged 10–24 years. There is an urgent need to respond to the changing global burden of adolescent mortality, address inequities where they occur, and improve the availability and quality of primary mortality data in this age group