The largest cost savings (43%) reported from calcium fortification programs came from prevented hip fractures in older women from Germany. Our study highlights that calcium fortification leads to a higher calcium intake, small benefits in children’s height and bone health and also important evidence gaps for other outcomes and populations that could be solved with high quality experimental or quasi-experimental studies in relevant groups, especially as some evidence of calcium supplementation show controversial results on the bone health benefit on older adults.Calcium supplementation and fortification are strategies widely used to prevent adverse outcome in population with low-calcium intake which is highly frequent in low-income settings. We aimed to determine the effectiveness and cost-effectiveness of calcium fortified foods on calcium intake and related health, or economic outcomes. We performed a systematic review and meta-analysis involving participants of any age or gender, drawn from the general population. We searched PubMed, Agricola, EMBASE, CINAHL, Global Health, EconLit, the FAO website and Google until June 2019, without language restrictions. Pair of reviewers independently selected, extracted data and assessed the risk of bias of included studies using Covidence software. Disagreements were resolved by consensus. We performed meta-analyses using RevMan 5.4 and subgroup analyses by study design, age group, and fortification levels. We included 20 studies of which 15 were randomized controlled trials (RCTs), three were non-randomised studies and two were economic evaluations. Most RCTs had high risk of bias on randomization or blinding. Most represented groups were women and children from 1 to 72 months, most common intervention vehicles were milk and bakery products with a fortification levels between 96 and 1200 mg per 100 g of food. Calcium intake increased in the intervention groups between 460 mg (children) and 1200 mg . Most marked effects were seen in children. Compared to controls, height increased 0.83 cm , plasma parathyroid hormone decreased −1.51 pmol/L, , urine:calcium creatinine ratio decreased −0.05, , femoral neck and hip bone mineral density increased 0.02 g/cm Dietary calcium intake in low-income settings is typically low, and around 3.5 billon people are considered to be at risk of calcium deficiency ,2. CalciRecommendations for calcium intake vary. For individuals over 19 years of age, a daily calcium intake of 1000–1300 mg is recommended ,6. The lHowever, new evidence has shown that adequate calcium intake also has health benefits beyond bone health . ApproprCalcium supplementation compared to placebo has shown a 55% (95% CI: 35 to 69%) of RRR of preeclampsia . In popuIn 2011, WHO guidelines for the prevention of preeclampsia recommended calcium supplementation with 1.5–2.0 g per day from 20 weeks pregnancy, particularly in a population with low calcium intake ,21. PrevFor these reasons, the discussion on calcium supplementation has moved in recent years to food fortification as a more effective means to achieve adequate levels of calcium intake and reaching entire populations. Food fortification has been identified as one of the most cost-effective interventions to address micronutrient deficiencies in populations . In addiIn this review and meta-analysis, we aimed assess the effectiveness and cost-effectiveness of commonly consumed food fortified with calcium on calcium intake and on selected clinically relevant health outcomes. This information could help to design a population-based food fortification implementation scheme, as a public health strategy to improve calcium intake.We performed a systematic review and meta-analysis following Cochrane methods , and theWe considered the following study designs: complete and incomplete economic evaluation or cost studies, randomized controlled trials, controlled before-and-after trials (CBA), uncontrolled before-and-after trials (UBA), interrupted time series (ITS) designs with at least three data points before and after the intervention, with or without comparison groups, and cohort studies. Systematic reviews were considered as a source of studies and other study designs were used only to describe the intervention.We included studies involving participants of any age or gender. We excluded those studies exclusively performed in special populations . We included populations with any levels of calcium intake and in any country, region or setting.We prioritized the inclusion of interventions of commonly consumed foods fortified exclusively with calcium. However, in their absence, we also included interventions that fortified foods with calcium salts, calcium from milk extracts, or commercially available foods with high calcium that allowed to increase calcium intake of the population. We included interventions where foods had the addition of calcium and/or other nutrients carried such as those minerals from milk , even if the increase of this other nutrients was only in the intervention group. We excluded those interventions where foods had calcium and vitamin D unless the same increment on vitamin D was also in the control group. We only included studies with calcium and vitamin D fortification when the outcome was dietary calcium intake, since there is no evidence that vitamin D interferes calcium intake. Otherwise, we only considered calcium fortification as an intervention. We included studies that compared the fortified food with similar unfortified food, with a food with lower content of calcium, with usual diet, or with supplement placebo.The primary outcome was calcium intake reported as mg per day, and health outcomes related to calcium intake such as bone health, bone metabolism, blood pressure, preeclampsia (for pregnant women), cardiovascular outcomes, hypertension, lithiasis, cholesterol, weight, height and body mass index (BMI). We also aimed to characterize the cost, cost-effectiveness and budget impact analyses of commonly consumed food fortified with calcium.We searched, from inception to 8 June 2019, PubMed, Agricola, EMBASE, CINAHL and Global Health. We did not apply language limitations or publication date restrictions for the search, however we only included studies in English and Spanish. For studies with multiple publications, we used the publication reporting more information. The search was performed on 9 December 2019. Two reviewers independently screened titles and abstracts in duplicate. We retrieved the full text of all potentially relevant studies. The full text of these studies were retrieved and read also in duplicate; those that fulfilled the aforementioned selection criteria were included in the review. Disagreements were resolved by consultation with a third reviewer, and agreement on discordant decisions was reached by consensus. We extracted data on study title, author, publication date, country, city, included population, setting, study design, intervention food, fortification level, comparison group and outcomes.https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools). Economic studies were assessed with the CHEERs checklist [Two reviewers independently performed quality appraisal for each study, and disagreements were resolved by discussion or consultation with a third reviewer. For randomized controlled trials (RCTs), we used the Cochrane risk of bias tool, which assesses selection bias, performance bias, detection bias, attrition bias, and reporting bias rating each component as “high”, “low”, or “unclear” for each risk of bias component. For Non-Randomized studies, we used the Study Quality Assessment Tools for critical appraisal of the internal validity of each type of study ), age group (Children and adults), menopausal status, level of fortification  and basal calcium intake. We calculated a pooled effect size for each subgroup. Due to the scarcity of data we couldn’t perform the analysis for WHO region and continent subgroups. The search strategy retrieved a total of 3186 and after removing duplicates, 2122 articles remained for title and abstract screening. A total of 1978 studies excluded for title and abstract screening and of the 144 articles screened for full text eligibility. Finally, 20 studies fulfilled the inclusion criteria, 18 for clinical outcomes , and two economic evaluations see . The 15 In general, the included studies were judged to be at unclear risk of bias due to insufficient information regarding sequence generation, blinding of outcome assessment, and selective reporting. The majority of the studies were judged to be at high risk for blinding of participants and personnel. The majority of the studies were at high risk of bias or there was insufficient information to assess for incomplete outcome data and other bias. In most studies the role of the food industry was not clarified. The summary of the risk of bias across the included studies is shown in Ten studies were from the WHO Western Pacific region ,42,45,46The most common intervention food vehicles were milk, evaluated in eleven studies ,46,47,48Fortification level was less than 500 mg per day in five studies ,47,48,49Sixteen studies were trials of which twelve ,45,46,47Considering an adequate intake above the IOM’s estimated average requirement (EAR) for calcium, two out of three studies including children aged 4 to 10 years, had adequate intake (EAR is 800 mg a day) ,42. NoneFour studies had a duration of less than 2 months ,38,39,48The main outcome reported in the studies was bone health for fourteen studies ,45,46,47We found that ten studies with a duration from 1 to 72 months reported calcium intake ,45,48,49We included two economic studies, one from the United States and the other from Germany. The study of Keller et al., from the United States aimed to assess the cost of calcium from a wide variety of sources in diverse cities of United States, while controlling for seasonal variations . The stuWe present the meta-analysis effect sizes, separately for RCT and Non- RCT. The Summary of findings is presented in 2 = 90%) in the calcium fortification group compared to the control group [2 = 89%) [Ten RCTs, lasting from 1 to 72 months, provided data for the calcium intake outcome ,46,48,49ol group ,36,45. T2 = 89%) ,41,46. O2 = 89%) .2 = 89%) [Of the three non–RCT reporting calcium intake, two were in adults and showed an increase in calcium intake of 639.6 mg per day,  ,49, and 2 = 89%)  , a medium fortification of 459–600 mg/day increased calcium intake in 258.1 mg/day (95% CI 218.7 to 297.5) and a high fortification of 676–900 mg/day increased calcium intake in 477.35 (95% CI 434.5 to 520.2): Test for subgroup differences:  = 96.7% .2 = 0%) in children, five RCTs with a duration from 8.5 to 24 months [The fortification intervention resulted on a body weight increase of 0.22 kg, , six RCT with a duration from 8.5 to 24 months [The estimated effect of the fortification intervention on height change in children was 0.83 cm,  one RCT with a duration of 24 months . In premThe estimated effect of the fortification intervention on plasma 25 hydroxy cholecalciferol (25 (OH) D3 in children was −0.60 ng/mL, (95% CI −1.28 to 0.08) one RCT with a duration of 24 months , whereas2 = 41%) two RCTs with a duration of 4 weeks and 6 months [The estimated effect of the fortification intervention on serum calcium in children was −1.60 mg/dL, (95% CI −1.79 to −1.41) one RCT with a duration of 24 months , whereas6 months ,43  one RCT with a duration of 24 months , whereas2, (95% CI 0.01 to 0.04 I2 = 0%), four RCTs studies with five subgroups and a duration from 11 to 24 months [2, (95% CI −0.04 to 0.03) in postpartum women, one RCT with a duration of 12 months [The estimated effect of the fortification intervention on Bone Mineral Density (BMD) Femoral neck in children was 0.02 g/cm4 months ,34,42,452 months   in one Non-RCT with a duration of 18 months [The estimated effect of the fortification intervention on BMD Femoral neck inpre-monopausal women was −0.01 g/cm8 months   four RCTs with five subgroups and a duration from 11 to 24 months [2, (95% CI −0.06 to 0.02) in postpartum women, one RCT with a duration of 12 months [The estimated effect of the fortification intervention on BMD Lumbar spine in children was 0.01 g/cm4 months ,34,42,452 months   in one Non–RCT study with a duration of 18 months [The estimated effect of the fortification intervention on BMD Lumbar spine in premenopausal women was 0.00 g/cm8 months   in two RCTs with a duration of 18 to 24 months [2, (95% CI −0.04 to 0.03) in postpartum women, one RCT with a duration of 12 months [The estimated effect of the fortification intervention on BMD hip in children was 0.03 g/cm4 months ,45, −0.02 months   in one Non–RCT study with a duration of 18 months [The estimated effect of the fortification intervention on BMD hip in pre-menopausal women was −0.01 g/cm8 months   three RCTs with a duration from 18 to 24 months [2, (95% CI −0.02 to 0.03) one RCT with a duration of 12 months [The estimated effect of the fortification intervention on BMD total body in children was 0.01 g/cm4 months ,42,45, w2 months   four RCTs with a duration of 1 to 18 months [The estimated effect of calcium fortification intervention on BMC total body in children was 11.59 g,  three RCTs with four subgroups with a duration of 1 to 24 months [The estimated effect of calcium fortification intervention on BMC lumbar spine in children was 0.69 g,  one RCT with a duration of 18 months . The estThe estimated effect of the calcium fortification intervention on BMD Trochanteric region in adults was −0.00, (95% CI −0.04 to 0.04) one Non–RCT study with a duration of 18 months  Figure .The following outcomes were reported in only one RCT showing no effect of calcium fortification intervention, total cholesterol −0.20, (95% CI −0.61 to 0.21); LDL cholesterol −0.20, (95% CI −0.51 to 0.11), HDL cholesterol , LDL/HDL Ratio −0.10, (95% CI −0.42 to 0.22), TAG 0.10,  Office sitting 0.00,   see Tab. 2), body mass index (kg/m2), bmc hip, Femoral neck and Femoral shaft (g), calcium intake by calcium fortification level (mg/day), parathyroid hormone by calcium fortification level (pmol/L), serum 1,25-dihydroxycholecalciferol by calcium fortification level (nmol/L), weight by calcium fortification level (Kg), BMD femoral neck, lumbar spine, hip and total body by calcium fortification level (g/cm2). None of the included studies reported preeclampsia, cardiovascular outcomes, hypertension or lithiasis.p = 0.01; femoral neck, p < 0.0000001). The women in the control group experienced a reduction in BMD at all sites; the reduction in BMD was only significant at the hip during 12 months (p = 0.008) and at the femoral neck during 18 months (p = 0.005). Finally, the study of Cleghorn [p = 0.006).Three RCTs were not included in the meta-analysis. Green et al. was the only trial reporting blood pressure. The four-week cross over RCT assessed the effect of a commercially available high calcium skim milk powder providing 1075 mg of calcium in 50 g of powder compared to normal skim milk powder with 720 mg of calcium in 50 g of powder in the blood pressure of 38 men and women aged over 40 years [Cleghorn  was exclWe explored the potential effect of phosphorus as a cointervention in all the outcomes and we did not find any difference between those with and without phosphorous as cointervention. We did not find important differences in the effect of fortification in the subgroup of studies before and after one year of intervention.Two studies were included for the economic synthesis. Keller et al. found that the cost of estimated absorbable calcium in the United States ranged widely from one product to another. The study found that the least expensive sources of calcium were cereal, skim milk and calcium-fortified orange juice from frozen concentrate, whereas other dairy products, such as mozzarella and low-fat yogurt, were considerable more expensive sources .Sandmann et al. showed that the total costs of an hypothetical vitamin D and calcium voluntary food fortification programme amounted to €41 million per year in Germany (currency euro 2013 year 2014): €33.1 million for cholecalciferol and calcium, €3.3 million for marketing and education activities, €2.9 million for food control and monitoring, and €2.1 million for other programme-specific recurrent production costs. On the other hand, €356 million in the cost of fractures were saved per year . The larWe found that fortification increased calcium intake in all studied age groups (moderate certainty-evidence) for children and low certainty-evidence for adults, indicating that fortified foods could be an effective way to help populations attain dietary calcium recommendations . Food foCalcium balance is hence actively controlled by a large number of factors. The external balance of calcium (the difference between intake and output) is, in effect, determined by the exchange between the skeleton, the intestine and the kidney. These fluxes are controlled by the action of calciotrophic hormones: parathyroid hormone; 1,25-dihydroxycholecalciferol; calcitonin. It is also influenced by other factors such as sex hormones, growth hormones, corticosteroids and a variety of locally-acting hormones. Vitamin K supplementation at doses obtainable in the diet from a 50 g portion of green leafy vegetables, in combination with calcium and vitamin D has been suggested to play a role in the optimization of bone health. We found one study reporting a decrease in PTH blood levels, calcaemia and urine calcium creatinine ratio in girls with low calcium intake and high prevalence of Vitamin D deficiency receiving a fortified milk compared to usual diet . It is dImportantly, none of the included RCTs reported adverse effects of calcium fortification alone or in combination with other minerals. However, the evidence we found in this review should be taken with caution as most RCTs were assessed as low quality, mainly due to lack of blinding and attrition bias. Except from the outcomes ‘calcium intake’ in adults and postmenopausal women, in which the certainty of evidence was low, for the remaining clinical outcomes considered, it was deemed moderate.Most food vehicles used for fortification identified in this review were dairy products, mainly milk. Other food vehicles were flour and bakery products. Most fortificants used to add calcium were milk-derived powders or salts, which besides calcium, added other minerals such as phosphorus and magnesium to the fortified foods. Phosphorus is known to participate in the calcium metabolisms and magnesium has been reported to also have effects on blood pressure and bone health . TherefoMost of the identified evidence came from upper-middle income countries that mostly had adequate calcium intake. This could be one of the reasons of the lack of important effects. Other reasons for absence of effect could be study duration, in children the duration was at least 12 months in four out of six studies, in adults there were four out of nine studies that lasted at least 12 months. Another reason could be the low fortification level, as some studies had a comparison group that also added calcium, leaving a net difference between the intervention and the comparison groups of less than 600 mg of calcium a day in eight out of 15 RCTs and only one more than 1000 mg a day.Evidence from market derived fortification in the US shows that the least expensive foods to fortified are cereals, skimmed milk and orange juice . From a We did an exhaustive search using a broad search strategy in most important databases following Cochrane methods and PRISMA statement for reporting. We also carefully explored grey literature and the reference lists in systematic reviews to detect more studies. We performed the risk of bias assessment and the Grade analysis and sensitivity analysis for subgroup.The main limitation of the review is the difficulty to isolate the effect of calcium alone. The evidence for food fortification with calcium alone is scarce so the effects we show are for calcium in combination with other minerals mainly those from milk such as phosphorus and magnesium that can also influence the health outcomes we studied. Although we did sensitivity analysis for those that had calcium alone as the intervention or combined interventions and found no difference. Besides, although the studies report the calcium fortification level provided per daily portion of food, the actual food intake was only reported by six of the 15 included RCTs. Another limitation is that we could not draw reliable conclusions from various subgroup analyses due to the restricted number of studies in each subgroup. In addition, most food vehicles evaluated were dairy products which are not highly consumed in many LMICs where most populations with low calcium intake are found.The documented evidence of the effects of calcium food fortification seems scarse, despite the existance of many calcium fortified foods in the market. This is in agreement with other recent reviews on the topic . Food foExcept for the economic evaluation and the before and after study from Osler et al. we found no evidence from large scale fortification programs which are important to measure the effect in real conditions . We did This review suggests that calcium fortification increased calcium intake in a dose-response fashion, suggesting a good acceptability and a feasible method to reach dietary recommendations. Even if the effects on height and bone health in children were found small, they deserve further considerations, due to its potential public health impact in the prevention of stunting and bone diseases. We did not find any statistically significant effect on weight, BMI, bone health, or metabolic parameters of adults. Our review highlights a substantial evidence gap on the effects of calcium fortified foods on blood pressure and bone fracture. There is a lack of studies on adolescents, men and pregnant women exploring the effect on blood pressure, bone health and weight. In addition, studies are needed to explore the effect of higher fortification levels, more appropriate comparison groups in the context of better powered trials and longer intervention periods as there is evidence that there could be a not long-lasting effect ,62. High


Brucella species. A total of 127 animals from 37 herds tested positive, giving overall individual animal and herd-level seroprevalences of 7.53% (95% CI: 6.28–8.78%) and 21.14% (95% CI: 15.0–27.2%), respectively. Namwala district had the highest herd seroprevalence , while Lundazi did not record any seropositivity. Comparably, Southern Province had the highest individual animal  and herd-level  seroprevalences, although this was not statistically significant. Within Southern Province, higher seropositivity was observed in Namwala district , among female animals  and in those aged 11 years and above  as well as in gravid cows . Seropositivity was also observed among some animals with hygromas  and those with a history of abortion  although the findings were not statistically significant. Brucella seroprevalence among traditional cattle in Zambia remains high. Control programs against bovine brucellosis must be introduced to reduce its impact on human health and animal production.Brucellosis is an infectious zoonosis that has huge economic and public health implications globally. The disease is prevalent in humans, livestock and wildlife in Sub-Saharan Africa. A cross-sectional study was conducted between 6 May 2017 and 31 July 2020 during which 1712 sera from 175 cattle herds in five districts from Southern, Western and Eastern Provinces of Zambia were collected and screened against brucellosis. The Rose Bengal Test (RBT) and competitive Enzyme-linked Immuno Assay (c-ELISA) were used in serial testing for the detection of antibodies against  Brucella, which currently contains 12 host-specific species [Brucella abortus is the main cause of brucellosis in cattle, other species have also been isolated [Brucella infections through occupational exposure to animals and the consumption of unpasteurized milk [Brucellosis is an infectious zoonotic disease of economic and public health importance that affects livestock, wildlife and humans worldwide . The disisolated ,4,5. Theisolated . Transmized milk . This unBrucella organisms, the bacteriological samples collected for culture often include milk [The diagnosis of brucellosis is performed using bacteriological, molecular and serological methods . Bacteriude milk , hygromaude milk , fetal mude milk ,10. Seroude milk . These tMost developed countries have managed to eradicate bovine brucellosis . HoweverIn Zambia, a few studies that were conducted in wildlife and cattle in Southern and Western Provinces almost eight years ago estimated the disease seroprevalence in smallholder and traditional cattle ,24,25,262, an estimated human population of 1,907,784 [2, a human population of 1,007,855 [This cross-sectional study was carried out in five districts that were purposively selected from three provinces of Zambia, namely, Namwala, Choma and Monze (Southern Province), Senanga (Western Province) and Lundazi (Eastern Province). This is because they have higher cattle populations in Zambia compared to other provinces. The traditional cattle breeds that are reared in the study areas are, namely, Tonga, Barotse and Angoni in Southern, Western and Eastern Provinces, respectively. Southern Province lies between latitudes 15°14′ S and 17°42′ S and longitudes 25° E and 28° S. It has a total land surface area of 85,283 km,907,784  and a ca,907,784 . Western,007,855  and an e,007,855 . Pastora2 ∗ p ∗ (1 − p)/d2, where z = 1.96, p = the expected herd seroprevalence of 32% [The required sample size was calculated using the formula n = ze of 32% , d = thee of 32% . The avee of 32% . The calA total of 1712 cattle from 175 herds were randomly sampled from five districts, namely, Namwala, Choma and Monze (Southern Province); Senanga (Western Province); and Lundazi (Eastern Province). This was performed by determining the sampling interval based on the number of herds available and the required sample size.cELISA test kit  as per the manufacturer’s instructions and as described by others [Five milliliters of blood was aseptically collected from the jugular vein into labelled sterile plain vacutainer tubes. In the field, the serum was separated using a portable field centrifuge and stored in pre-labelled cryovial tubes at −20 °C until transportation to the University of Zambia for laboratory analysis. All the serum samples were screened for Brucella spp. antibodies using The Rose Bengal test kit  according to the test procedure recommended by the OIE Terrestrial Manual [y others . A samplBrucella prevalence. The individual animal seroprevalence was calculated by dividing the number of RBT- and c-ELISA-positive animals by the total number of animals that were tested. The herd-level seroprevalence was calculated by dividing the number of herds with at least one reactor on the RBT and c-ELISA by the number of all the herds tested. Associations between hypothesized risk factors and the outcome variables were assessed, and statistical analysis was performed using Chi-square tests and logistic regression using the statistical software STATA® version 16 .Data were entered into a spreadsheet , and the proportions were estimated for the individual and herd A total of 129 animals from 37 herds were seropositive, giving overall individual animal - and herThe odds ratios suggested that animals in Namwala were more likely  to test positive than those from the other districts. Furthermore, animals aged 11 years and above were more likely  to test positive than those from other age groups. On the other hand, gravid cows , those with a history of abortion  and those with hygroma  were more likely to test positive .Brucella seropositivity in Lundazi district, Eastern Province, is inconclusive, as it may be attributed to the small sample size; however, it is interesting to note that a seroprevalence of 7.7% was observed in Northern Malawi [This study aimed at estimating the seroprevalence of bovine brucellosis in selected districts of Zambia. The overall seroprevalences at the animal and herd levels were 7.53 and 21.14%, respectively. Although we did not detect any seropositivity in Eastern province, Southern Province had the highest herd and individual animal seroprevalences, respectively (28.5 and 8.97%), followed by Western province (10.0 and 8.35%). The individual animal seroprevalence in this study was slightly higher than the 6% reported in smallholder dairy cattle in Lusaka and Southern Provinces . The hern Malawi , which bOur herd seroprevalence is comparatively lower than the 25.6, 29.2, 32, 40.1 and 45.9% reported in Ethiopia, Tanzania, Cameroon, Nigeria and Angola, respectively ,16,17,21Brucella status. Animals aged 11 years and above were more likely  to test positive than other age groups. On the other hand, gravid cows , those with abortion histories  and those with hygroma  were more likely to test positive. It has been documented that female and older animals tend to have increased chances of testing positive for Brucellosis [Brucella organisms become high [Brucella organisms increases with age. The high seropositivity observed among females could also be due to the high number of females that were sampled compared to males. The high seroprevalence among pregnant cattle can be explained by the elevated erythritol levels in the placental and fetal fluids during the third trimester [Although statistically not significant, the seropositivity was higher in female animals (8.45%), those aged 11 years and above (14.1%) and gravid cows 13.79%). This agrees with findings from similar studies .79%. Thi,24,35 ancellosis . As the ome high , while crimester . These hThe combined use of RBT and cELISA tests serially in our study maximized the specificity of the test system, while reducing labor and costs. The RBT was used as a cheap and easy-to-perform screening test with high sensitivity but limited specificity. To improve the specificity of the test system, only RBT-positive reactors were confirmed by the expensive and laborious but highly sensitive and specific cELISA. Thus, as far as misclassification bias is concerned, the seroprevalence estimates in our study may be assumed to be unbiased.Brucella seroprevalence seems to have maintained enzootic stability over a decade in Southern and Western Provinces. There is a need to develop and implement multisectoral One Health surveillance and control strategies to minimize the disease burden in animals and, consequently, in humans.The overall brucellosis seroprevalence rates at the individual animal and herd levels were 7.53 and 21.14%, respectively. The seropositivity was higher in female animals, those aged 11 years and above and gravid cows, although this was not statistically significant. It is interesting to note that the


Senticol 2 is a randomized multicenter trial in the treatment of early-stage cervical cancer patients. The aim of the Senticol 2 study was to compare the effect of sentinel-lymph-node biopsy (SLNB) to that of SLNB + pelvic lymphadenectomy (PLND), and to determine the postoperative lymphatic morbidity in the two groups. Here, we report a secondary objective of this study: the follow up.In the Senticol 2 trial, patients underwent a laparoscopy with a sentinel-node-detection procedure and were randomized into two groups, namely: Group A, in which participants received SLNB, and Group B, in which participants received SLNB + PLND. Patients with an intra-operative macroscopically suspicious lymph node, were given a frozen-section evaluation and were randomized only if the results were negative. All of the patients received follow up with a clinical examination at 1, 3, and 6 months after surgery, and then every 3–4 months after that. The median follow up was 51 months (4 years and 3 months).p = 0.53), respectively. The only statistical factor associated with recurrence in the univariate analysis was the adjuvant radiotherapy. No other factors, including the age of the patients, histological type, tumor size, lymph vascular space invasion (LVSI), and positive nodal status, were significant in the univariate or multivariate analyses. The overall survival rates after 4 years in the SLNB and SLNB + PLND groups were 95.2% and 96% (p = 0.97), with five and four deaths, respectively. The univariate and multivariate analyses did not find any prognostic factors.Disease-free survival after 4 years for the SLNB group and the SLNB + PLND group were 89.51% and 93.1% (This randomized study confirmed the results of the Senticol 1 study and supports the sentinel lymph node (SLN) technique as a safe technique for use in patients with early-stage cervical cancer treated with SLNB only. Disease-free survival after 4 years was similar in patients treated with SLN biopsy and patients who underwent a lymphadenectomy. Cervical cancer results in over 300,000 deaths worldwide every year .Advances in cervical-cancer screening have resulted in a lower incidence of cervical cancer but a higher incidence of early-stage disease diagnosis in developed countries , 3. One It has been demonstrated that the lymph-node status directly impacts the 5-year survival rate of patients with International Federation of Gynecology and Obstetrics (FIGO 2009) Stage IA1 to IIB cancers .According to the international guidelines for the treatment of early-stage cervical cancer, the gold-standard treatment includes pelvic-lymph-node dissection (PLND) in order to adapt the treatment to a potential lymphatic metastasis. In the Senticol 1 trial , we demoA lymph-node metastasis is present in 27% of early cervical cancers, leading to a high rate of overtreatment with unnecessary PLND in three out of four patients . MoreoveA SLNB procedure can accurately detect metastases for several other diseases such as breast, penile, skin, and vulvar cancer. In 2015, the National Comprehensive Cancer Network (NCCN) Guidelines  stated tFurthermore, we showed previously that an SLN biopsy can decrease both early and long-term morbidity and can improve quality of life compared with a complete pelvic lymphadenectomy .The aim of this study was to assess the disease-free survival and overall survival of early-stage cervical cancer patients included in the randomized controlled multicenter Senticol 2 study.The Senticol 2 protocol  was approved by an ethics committee  and all of the patients provided written informed consent before inclusion.We performed a randomized controlled trial from December 2008 to November 2011. A total of 25 centers were included, all surgical team were experimented (>20 cases). The number of cases per center and the name of the surgeon is described in Patients were followed for a minimum of 3 years after their inclusion in the study.The inclusion criteria were as follows: Women aged 18 or older diagnosed with cervical carcinoma of FIGO 2009 stage IA1 with LVSI, to IIA1, including any histological subtype (except neuroendocrine carcinoma). The patients were eligible for laparoscopy and written informed consent was obtained from all of the patients.The exclusion criteria were as follows: Pregnant women, stage IB (by downstaging), evolving or recurrent cervical cancer, other cancer diagnosed during treatment, history of pelvic node surgery, or severe allergy or contraindication to radioactive tracer or Patent Blue.®, CIS Bio International) on the day of  or the day before the surgery , after which 2 mL of vital dye  diluted with 2 mL of water was injected into the cervix at the 3, 6, 9, and 12 o’clock positions.All patients received injections of the radioactive tracer colloidal rhenium sulfide labeled with technetium , and Group B, which received SLNB + PLND.The patients with intra-operative macroscopically suspicious sentinel or eventually non sentinel lymph nodes (NSLNs) received a frozen-section evaluation and were randomized only if the results were negative.All of the SLNs were analyzed using the histological ultrastaging method (200 µm sections) and were stained with hematoxylin eosin saffron (HES) or hematoxylin phloxine saffron (HPS). An additional immunohistochemistry (IHC) analysis with a pan-cytokeratine antibody was performed in case of a negative SLN.For the definite node-negative patients, we proceeded with an additional surgery—either a radical hysterectomy or radical trachelectomy ). Adjuvant treatments were defined following the final histology.For the definite node-positive patients, we proceeded with an additional treatment using chemo-radiotherapy after first considering a laparoscopic para-aortic lymphadenectomy.All of the patients received clinical examination follow ups 1, 3, and 6 months after surgery, and then every 3–4 months afterwards. The median follow-up duration was 51 months.p < 0.15. The multivariate analysis of the recurrence-free survival was performed using a Cox’s proportional hazard model. All of the analyses were performed on an intention-to-treat basis.Disease-free survival rates were estimated using the Kaplan Meier method. The survival curves were compared with a Log-rank test . Recurrence-free survival was defined as the time from surgery to disease recurrence or death due to any cause. A second analysis regarding patients with no evidence of recurrence or death was done at the date of the last follow-up. A multivariate analysis was performed including factors with Between December 2008 and November 2011, 267 patients participated in Senticol 2. Of these, 61 patients were excluded—2 (3.3%) had not had a lymphoscintigraphy before surgery, 12 (19.7%) had an incomplete SLNB procedure, 11 (18%) had an absence of SLN detection, 21 (34.4%) had a unilateral detection of SLN, and 15 (24.6%) had positive SLN on the frozen sections.A total of 206 patients were randomized, with 105 patients assigned to Group A (SLNB) and 101 to Group B (SLNB + PLND).The baseline characteristics of the patients at inclusion are summarized in ®) diluted with 2 mL of water injected into the cervix at the 3, 6, 9, and 12 o’clock positions. We had no cases with discrepancy between the lymph-nodes marked with patent blue and lymph-nodes marked with technecium. During the SLN procedure, there was no difference in sentinel mapping between the two groups , with a radical hysterectomy rate of 78.7% and 80.5%, a radical trachelectomy rate of 16.9% and 13.4%, and a simple hysterectomy and trachelectomy rate of 4.5% and 6.1%, respectively.The surgical approaches were similar in the two groups (p = n.s.). In this group there were 9 positive SLN and 1 positive NSLN in a patient with a positive SLN also. The correspondence between SLN and NSLN was 100%.The final histological analysis (including ultrastaging) of the SLNs indicated 12 (11.4%) patients with a positive node in the SLNB group  and 9 (8.9%) patients with a positive node in the SLNB + PLND group  , with a median of 51 months (4 years and 3 months).p 161 = 0.53), respectively. There was no significant difference between the two groups. There were 11 recurrences in the SLNB group and 7 in the SLNB + PLND group . In the univariate analysis, none of the risk-factor covariates that were analyzed were statistically significant for any of the clinical events at a p = 0.05 level. However, a trend could be observed, depending on the case, for the covariates—namely adjuvant radiotherapy and LVSI. When we retained covariates with a p-value of <0.15 in the univariate analysis in a multivariate model, none were statistically significant . The overall survival (OS) for the patients who received SLNB was 95.2, and 96% for those who received SLNB + PLND  IA1 to IIA1, the SLN procedure alone did not result in a significant disease recurrence compared to complete pelvic lymph-node dissection. In addition, no significant difference was found in the overall survival between the two groups.Considering that a great majority of recurrences normally appear within 3 years after treatment, SLNB seems to be a safe and efficient alternative to lymphadenectomy, and should be proposed to every patient as a routine protocol for early-stage cervical cancer in cancer centers where surgeons are familiar with this technique and follow the correct SLN protocol. It should still be considered that the study was not designed to compare the survival and the risk of recurrence between the two groups (SLNB and SLNB + PLND). This subgroup of patients with early-stage cervical cancer indeed had a good survival with a low recurrence rate. In conclusion, too few events were observed during long-term follow up (4 years) to allow for a tangible analysis of the risk factors for survival or disease-free survival.However, this was the first randomized controlled prospective study evaluating the follow up of SLNB alone in comparison with SLNB + PLND, and it confirmed the Senticol 1 results.p = 0.02). This result can be explained by the fact that the patients who presented major risk criteria (according to the Seidlis criteria)   were trevia laparoscopy. Open surgery was performed only in the case of complications during laparoscopic surgery. It is interesting that in our study, we found a survival and disease-free survival similar to that of the open-surgery group in Ramirez’s study. This comparison is limited, as our study was designed for laparoscopic treatment and there were a large number of cases where the colpotomy was performed vaginally with protective measures. A vaginal colpotomy may protect from the risk of tumor dissemination and recurrence  affected by early cervical cancer.A strong and influential study called Senticol 3  and SentThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Comité de Protection des Personnes Sud-Est IV, decision A08-223. The patients/participants provided their written informed consent to participate in this study.Conceptualization, GF, VB, BG, FL, and PM. Methodology, LM. Software, LM. Validation, VB, FL, BG, and PM. Investigation, FL and PM. Resources, BG, PM, and FL. Data curation, GF, BG, PM, and FL. Writing—original draft preparation, GF and BG. Writing—review and editing, GF, VB, FL, BG, and PM. Visualization, GF, VB, FL, BG, and PM. Supervision, FL and PM. Funding acquisition, PM. All of the authors have read and agreed to the published version of the manuscript. All authors contributed to the article and approved the submitted version.The Senticol 2 study was supported by the French National Cancer Institute (STIC 2008 and 2012). The study sponsor had no role in the design or conduct of the study, interpretation of data, or the writing of the report.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Erythrocyte alloimmunisation can lead to complications such as delayed haemolytic transfusion reaction.This study investigated the prevalence of and risk factors for red blood cell alloimmunisation among multiply transfused sickle cell disease (SCD) patients in Mwanza City, Tanzania.From May 2017 to July 2017, this descriptive, cross-sectional, hospital-based study enrolled 200 participants with SCD who had received at least two units of blood in the previous year. Blood count was performed using a Sysmex haematology analyser. Antibody screening was done by the tube method using a panel of three screening cells with known antigenicity.Of the 200 patients enrolled, 108 (54%) were female. The median age was 4.5 years (interquartile range [IQR] = 6), the median number of transfusions was 3 (IQR = 1), and the median pre-transfusion haemoglobin level was 6.6 g/dl (IQR = 2.7). Prevalence of alloimmunisation was 8.5% (17/200) with immunoglobulin G, and one patient developed cold immunoglobulin M antibodies. Blood groups reported were Rhesus C and E, Kell, Kidd and Duffy. There was no statistically significant association between the number of transfusions and the risk of alloimmunisation.The rate of alloimmunisation in multiply transfused SCD patients was 8.5% and higher than other studies in East Africa. Thus, there is a need for extensive red blood cell screening and matching to minimize alloimmunisation and risk of delayed haemolytic transfusion reaction, particularly in SCD and chronically transfused patients. Globally, approximately 300 000 people are born with SCD annually.3 In Africa, including Tanzania, and the Middle East, the ABO and Rhesus D blood grouping system are as the test parameters for blood transfusion, neglecting other red blood cell surface antigens, which are considered minority blood groups. However, this can cause serious complications, including alloimmunisation in SCD patients, once a transfusion is done, without a thorough and complete screening of the antigenicity of both the donor and the recipient.4Blood transfusions are necessary for the care and treatment of patients with SCD.5 Complications of alloimmunisation include life-threatening conditions such as delayed hemolytic transfusion reactions, immediate agglutination, hyper hemolysis2 and autoimmune responses in individuals having blood transfusions, especially SCD patients.Alloimmunisation is the body’s response to foreign antigens after being subjected to cells or tissues with different antigenicity.6. The presence of alloantibodies is a major complication in SCD, presenting challenges for medical management. Antigen matching beyond the standard ABO blood grouping system and Rhesus typing has reduced complication rates.6 According to Bashawri et al., race and ethnicity could be a risk factor for alloimmunisation in sickle cell anaemia patients.7 Additionally, failure to screen for minor antigens such as Kidd, Duffy, and MNS blood groups, might cause a mismatch and subsequent alloimmunisation in blood recipients.8.Studies have shown that antigenicity matching, for SCD and chronically transfused patients, is important for decreasing the frequency of alloimmunisation and its associated complicationsCurrent practice in Tanzania is forward grouping, which screens for blood groups ABO and Rhesus D. However, there are currently no guidelines for blood group screening at the National Blood Transfusion Services. Thus, patients are typically transfused without an extensive matching for compatibility. For example, no screening for Kell antigens is conducted. Additionally, little is known about the extent to which alloantibodies affect sickle cell patients locally.This study aimed to examine the prevalence of developing red blood cell alloimmunisation among multiply transfused SCD patients and identify its associated risk factors, especially in Mwanza (Lake Zone). This will, in turn, be valuable for the setting up of guidelines for extensive donor and recipient typing, especially for transfusion-dependent patients at Bugando Medical Centre (BMC)/Lake Zone National Blood Transfusion Services laboratories.Ethical clearance was received from the Catholic University of Health and Allied Sciences and BMC joint research committee . Permission to work in the BMC Central Pathology Laboratory was also sought from the Laboratory Director and Manager. Written informed consent was sought from both inpatient and outpatient SCD with multiple transfusions before including them in the study.This was a cross-sectional study conducted from May 2017 to July 2017 at the BMC, Mwanza City (Lake Zone), Tanzania. Participants were inpatients and outpatients with SCD who attended the BMC during the study period and consented to participate. Patients were recruited until the estimated minimum sample size of 200 SCD patients was reached; the sample size was estimated using the Kishi Lisle Formula. The study included all SCD patients attending BMC inpatient and outpatient departments for transfusion therapy purposes who had received at least two units of blood during the previous year The study excluded patients with no blood transfusion history and patients who did not consent to participate. A structured questionnaire was completed by the parent or guardian of the child and laboratory records confirmed SCD, number of transfusions and interval of blood transfusion. The questionnaire was used to gather the demographic and medical history information of selected participants.One 4-ml blood sample was collected from each patient by phlebotomists at the Central Pathology Laboratory at BMC into ethyldiammine tetraacetate tubes to avoid agglutination and preserve red blood cell (RBC) antigenicity. Samples were stored at 2 °C – 6 °C refrigeration for not more than 3 days.1WR1; screen cell 2, product code R2R2; and screen cell 3, product code rr) . Screening for the different RBCs antigens was done as described by the manufacturer. Screen cell 1 had C, D, e, Cw, M, N, s, P1, K, k, Leb, Fya, Jka, and Jkb red cells. Screen cell 2 had D, E, c, M, S, P1, k, Leb, Fyb, and Jkb red cells, and screen cell 3 had c, e, N, s, P1, k, Kpa, Lea, Fyb, and Jka red cells  was added to the washed cells, mixed and centrifuged at 1500 revolutions per minute for 3 min. The centrifuged mixture of patient RBC and anti-human globulin was read microscopically for agglutination. Tubes with agglutination were considered ‘positive’ for autoantibodies, whereas tubes with no agglutination were considered ‘negative’ for autoantibodies. To rule out anti-human globulin non-reactivity and validate negative results (tubes without agglutination), pre-sensitised commercial RBCs  coated with short-armed antibodies were added. If agglutination was observed, which was expected, then anti-human globulin was reactive and the patient’s result was considered valid.P < 0.05 was considered statistically significant.After cross-checking, data were transferred directly to Statistical Package for Social Sciences software  version 20 and analysed. Continuous data were presented using medians and interquartile range, and the Chi-square was used to test associations for categories available. The median age of the study participants was 4.5 years (range: 0–26 years) . Of the p = 0.07]. The median number of transfusions for patients without alloantibodies was 2 (median: 1.0) units of blood. All 183 patients who were negative for warm alloantibodies received ≤ 2 transfusions.A total of 17 (8.5%) patients developed 23 warm alloantibodies and 183 (91.5%) tested negative for warm alloantibodies . Of the a), 1 was of the Duffy group (Fya) and 1 was of the Lewis group (Lea) , 6 were of the Kell group (anti-K), 2 were of the MNS group (anti-M), 1 was of the Kidd group (Jkup (Lea) .10 The differences in these rates could be attributed to differences in the median number of blood transfusions, which was lower  units) in the other two studies, whereas the mean number of transfusions at BMC was 3(1) units. The alloimmunisation rate of the current study was comparable to that reported by Ugwe et al.3 of 9.3%. The study included 145 SCD patients in Nigeria; blood transfusion was found to be significantly associated with alloimmunisation (p = 0.027 where p < 0.05). As with our study, sex was not statistically significantly associated with the risk of alloimmunisation in all three studies.The alloimmunisation rate in the current study is higher than the 6.1% alloimmunisation rate reported by Natukunda et al. in Mulago Kampala Uganda and the 4.1% rate reported by Meda et al. in Muhimbili Dar es salaam, Tanzania.11 The detection of alloantibodies of the Kell, MNS, Kidd, Duffy and Lewis blood groups is common12 and is corroborated by our study as Anti-C, anti-c, Anti-E, anti-e, Anti-K were the most common alloantibodies detected. Thus, these RBC antigens should be included in extended blood typing to detect alloantibodies to these groups. Warm alloantibodies (often IgG) are of clinical importance because they haemolyse red blood cells at body temperature whereas cold antibodies (IgM) also known as nuisance antibodies rarely haemolyse red blood cells in vivo due to temperature inactivation.13As of 2018, Tanzania was the third leading country in Africa for sickle cell anaemia after the Democratic Republic of the Congo and Nigeria.14. Thus, the prevalence and risk factors for red blood cell alloimmunisation in this locale needs to be identified. This study found an alloimmunisation rate of 8.5% among SCD patients at BMC in Mwanza, Tanzania, but found no significant association between alloimmunisation and the increased number of transfusions.In Tanzania, the Lake Zone area is leading with SCD patients  hence the numerous transfusions as part of their clinical managementMultiple transfusion is a risk factor for alloimmunisation, especially in sickle cell disease patients. However, in our study, multiply transfusion was not significantly associated with alloantibody development. This could be, in part, due to the small sample size, under-reporting and maybe because all participants had received blood transfusion at least once. More than half of the participants’ guardians or parents could not remember the actual number of blood transfusions a child had taken before attending BMC, thus influencing our final results. Availability of commercial red cells is a problem because there are few Haematological laboratories worldwide that can manufacture these red cells to cover the demands.Our antibody screening/identification approach might be prohibitive for extensive antibody screening in institutions with larger samples requiring shorter turnaround time because it is labour intensive and time-consuming. Other methods like Gel, SPRCA, or even automated methods can be used as these are faster, thus reducing laboratory turnaround time.Due to the common occurrence of alloantibodies and its detection within multiply transfused SCD patients in BMC, the BMC blood bank and Zonal National Blood Transfusion Centre should obtain facilities and expertise that will allow for extensive phenotypic blood typing and matching to minimise the development of alloantibodies and effectively minimize risks of delayed haemolytic transfusion reaction in SCD and chronically transfused patients.The rate of alloimmunisation in multiply transfused SCD patients was 8.5% and higher than other studies from East and West Africa. Thus, there is the need for extensive red blood cell screening and matching to minimize alloimmunisation and risk of delayed haemolytic transfusion reaction, particularly in SCD and chronically transfused patients.


The results revealed the formation of chitosan-fungicides nanoparticles could reduce the phytotoxic effect on oil palm seedlings compared to their counterparts, pure fungicides. The chitosan-fungicides nanoparticles were seen to greatly reduce the phytotoxic effect compared to the conventional fungicides with the same active ingredient.Although fungicides could be the best solution in combating fungal infections in crops, however, the phytotoxic level of fungicides to the crops should be tested first to ensure that it is safe for the crops. Moreover, nanocarrier systems of fungicides could play a significant role in the advancement of crop protection. For this reason, chitosan was chosen in the present study as a nanocarrier for fungicides of hexaconazole and/or dazomet in the development of a new generation of agronanofungicides with a high antifungal potent agent and no phytotoxic effect. Hence, the encapsulation of fungicides into the non-toxic biopolymer, chitosan was aims to reduce the phytotoxic level of fungicides. In the present study, the  Ganoderma boninense (G. Boninense) is one of the most serious problems in oil palm cultivation. The fungus causes severe damage to the infected oil palm with a significant loss in the crop yield, hence shorten the productive life of oil palm [Fungicides are compounds that control the fungal disease by destroying and inhibiting the fungus or fungal spores that cause the disease , wherebyoil palm . Upon inoil palm , 3G. boninense in vitro antifungal activity study, as well as in infected palm. During the experiment, conventional hexaconazole-based was used as a curative control by applying it in the standing Ganoderma-infected palm with the help of a hand-knock injector. The findings show that 74.4% of the treated palm remained alive and produced fruit bunches up to five more years while none from the untreated palm [Fungicidal treatments of hexaconazole and dazomet have been proved to inhibit the growth of ted palm . Hexaconted palm . Apart fGanoderma inoculum in the infected palm stump, therefore, minimizing the spread of Ganoderma disease within the oil palm plantation [Moreover, conventional dazomet-based fumigant was used as a preventive control by eradicating the antation . Dazometantation , 10. MITantation –13. Aparantation .A non-toxic biopolymer of chitosan nanoparticles has been widely used as a carrier of agricultural active ingredient  in crop protection , 16. ThePisum sativum plants [Nevertheless, it has been argued that the adoption of fungicides tends to affect plant physiology including growth reduction, perturbation of reproductive organ development, carbon metabolism, photosynthesis, and nitrogen alteration despite its ability to control the plant-fungal disease –24. Hexam plants . The phym plants .in vivo phytotoxicity effect on the vegetative growth of oil palm seedlings concerning 2 nm of chitosan nanoparticles (CEN), pure hexaconazole, conventional hexaconazole, pure dazomet, conventional dazomet and the three newly-developed systems of chitosan-based agronanofungicides, namely, single-loaded hexaconazole system  [Hence, the purpose of the present study was to determine the s, CHEN) , single-s, CHEN) , and dous, CHEN) . In eachs, CHEN) –29. In ts, CHEN) . MoreoveTenera (dura × pisifera) were obtained from the Malaysian Palm Oil Board (MPOB), Kluang. Oil palm germinated seeds (10 days old) of commercial Tenera (dura × pisifera) were obtained from the Malaysian Palm Oil Board (MPOB), Kluang.CEN (2 nm), CHEN (18 and 168 nm), CDEN (7 and 32 nm), CHDEN (5 and 58 nm) were formulated as previously described –29. Oil The nursery trial was conducted at the Malaysian Palm Oil Board (MPOB)’s nursery located at Seksyen 15, Bandar Baru Bangi, Selangor, Malaysia. The experiment was carried out in a randomized complete block design (RCBD) with twelve treatments , where HGerminated seeds of oil palm except healthy control were sprayed first with the prepared treatment solution. Then, healthy germinated seeds of oil palm were planted in a soil mixture  of polyethylene bag (8 × 12 inches) containing one seed per pot, and watered regularly. Every month, each pot was sprayed (foliar spray) with the treatment solution. The healthy control was germinated seeds, poured with tap water. The phytotoxicity was assessed at 1, 2, and 4 months after the first treatment. The observations included the height of seedling upper the soil, root elongation, dry weight and leaf area at monthly intervals.2 concentration were about 70%, 33–36°C and 370–390 μmol.mol-1, respectively. The rate of 1000 μmol CO2 m-2 s-1 was used as the light-saturated rate of photosynthesis.A final observation on chlorophyll content and gas exchange was done at 4 months after sowing. All measurements were carried out between 09:00 until 11:00 with the relative humidity of the air, ambient temperature and ambient COPn), stomatal conductance (Gs), and concentration of intercellular CO2 (Ci) were measured on fully expanded leaves seedlings using CIRAS-3 Portable Photosynthesis System . Chlorophyll content was determined with the Chlorophyll Meter, SPAD-502, Konica Minolta . These measurements were made on five randomly selected seedlings for each treatment with three replicates.The net photosynthetic rate (p ≤ 0.05) using the SPSS software.Data are presented as mean ± standard deviation and the statistical difference of the parameters was analyzed using the ANOVA and Tukey’s test , stomatal conductance (Gs), intercellular CO2 concentration (Ci) and total chlorophyll in leaves of survived oil palm seedlings at 4 months after sowing are presented in The phytotoxic effect of oil palm seedlings untreated and treated with various treatments on net photosynthesis rate  but still higher Pn value  compared to the healthy seedlings. However, a decrease in the Pn value was observed in the seedling treated with 5 nm CHDEN and 58 nm CHDEN by 10% and 7%, respectively, versus the healthy seedling.The recorded chlorophyll content showed a 38% and 32% decrease compared to the healthy seedlings for conventional dazomet and pure dazomet, respectively. Meanwhile, the other treatments showed no significant difference compared to healthy seedlings. Compared to the healthy seedlings, the E value with 65% and 36% decrease, respectively, compared to the healthy seedlings. Meanwhile, pure hexaconazole showed an 11% decrease in the E value compared to the healthy seedlings. Similar to Pn value, 2 nm CEN, 18 nm CHEN, and 7 nm CDEN exhibited a remarkable high E value with 160%, 113%, and 92% improvement, respectively, compared to the healthy seedlings. On the other hand, the larger size system, 168 nm CHEN and 32 nm CDEN exhibited lower E value  but still showed a 45% and 29% improvement compared to the healthy seedlings, respectively. Moreover, 5 nm CHDEN and 58 nm CHDEN showed the lowest E value among the chitosan-based agronanofungicides treatments with statistically similar E value to the healthy seedlings.On another note, conventional dazomet and pure dazomet showed the lowest Gs value of pure hexaconazole, conventional dazomet, and pure dazomet decreased significantly by 19%, 42%, and 49%, respectively, compared to the healthy seedlings. Similar to Pn and E value, 2 nm CEN, 18 nm CHEN, and 7 nm CDEN exhibited remarkably high Gs value with 97%, 96%, and 82% improvement, respectively, versus the healthy seedlings. Moreover, the larger size system, 168 nm CHEN and 32 nm CDEN exhibited lower Gs value  but still showed a 32% and 19% improvement, respectively, versus the healthy seedlings. Again, 5 nm CHDEN and 58 nm CHDEN showed the lowest Gs value among the chitosan-based agronanofungicides treatments with 28% and 3% decrease, respectively, compared to the healthy seedlings. Moreover, Ci value exhibited a negligible significant difference between the healthy seedlings and seedling treated in all treatments.In addition, Pn, E, and Gs established that 2 nm CEN, 18 nm CHEN and 7 nm CDEN were capable of producing more food by converting the light energy, carbon dioxide and water to carbohydrate (glucose) as shown in The results of Pn, E, and Gs value, as the larger size system, 168 nm CHEN and 32 nm CDEN produced lower Pn, E, and Gs value compared to their same system but in a smaller size. This indicated the importance of the size of chitosan-based agronanofungicides in improving the photosynthetic efficiency of oil palm seedling. However, 5 nm CHDEN and 58 nm CHDEN exhibited lower Pn, E, and Gs value compared to the other chitosan-fungicides nanoparticles system. This may be due to the double-loaded of hexaconazole and dazomet, which then increases the toxic effect on the chlorophyll content and photosynthesis rate of the oil palm seedlings.The effect of particle size can be seen in the The encapsulation of fungicide (hexaconazole and/or dazomet) into the chitosan nanocarrier has significantly reduced the direct phytotoxic effect of the fungicides. This is presumably due to the biocompatibility, biodegradability, and nontoxicity of the natural biopolymer, chitosan . ChitosaMoreover, the chitosan encapsulation has been documented to boost fungicide solubility, enhance absorption and site-specific delivery, as well as provide a slow and sustained release . As repoApart from that, no effect of different particle sizes of seedlings treated with the chitosan-based agronanofungicides in the physiological parameter  as well as the percentage of the desiccated leaves and dead seedling. No significant effect was observed in the growth parameter and plant health between the two range sizes of CHENs (18 and 168 nm), CDENs (7 and 32 nm) and CHDENs (5 and 58 nm). This suggested that the growth parameter and plant health were not affected by the particle size of the chitosan-based agronanofungicides. The chitosan nanocarrier itself is enough to shield the phytotoxic effect that comes from the fungicides, therefore showing a high potential of the chitosan-fungicides nanoparticles as the new generation of agronanofungicides with high antifungal efficacy and no phytotoxic effect.Robusta coffee which enhanced their photosynthetic activity and plant growth [However, the particle size on the single-loaded fungicide of CHENs and CDENs does show an effect on the photosynthetic efficiency in the leaf of the oil palm seedlings, where 2 nm CEN and the smaller size system, 18 nm CHEN and 7 nm CDEN have shown 88%, 71% and 70% improvement in the photosynthesis activity, respectively, compared to the untreated seedlings. This is in agreement with the previously reported work in the supplementation of chitosan nanoparticles in t growth . This suGanoderma boninense. Moreover, the smaller particle size of the chitosan-based agronanofungicides had shown the higher antifungal activity on Ganoderma boninense [50) on Ganoderma boninense is 1534.5, 21.4, and 152.2 ng.mL-1 for 2 nm of chitosan nanoparticles, hexaconazole, and dazomet, respectively. Moreover, the lower EC50 value has been obtained for the chitosan-based agronanofungicides with 8.0, 10.8, 4.6, 20.7, 3.5, and 13.3 ng.mL-1 for 18 nm CHEN, 168 nm CHEN, 7 nm CDEN, 32 nm CDEN, 5 nm CHDEN, and 58 nm CHDEN, respectively.This is the ideal desired properties for the agronanofungicides for better management of basal stem rot disease of oil palm developed in this work. As previously published, the encapsulation of chitosan enhanced the fungicide solubility and antifungal activity on oninense –29. The In summary, the results of the phytotoxic studies revealed the importance of chitosan and its size in reducing the phytotoxicity effect of fungicide in oil palm seedlings. All chitosan-based agronanofungicides have efficiently reduced their phytotoxic impact on oil palm seedlings compared to their counterparts, pure and conventional fungicide. Conventional hexaconazole and dazomet exhibited a strong phytotoxic effect on oil palm seedlings, rendering it harmful to be used in the treatment of fungus of oil palm seedlings. Hexaconazole showed a high impact on the vegetative growth of oil palm seedling, which resulted in growth retardation. On the other hand, dazomet showed an acute phytotoxic effect on oil palm seedlings by showing a high number of desiccated leaves resulting in dead seedlings. On another note, the smaller particle size of chitosan-based agronanofungicides was found to improve the photosynthetic efficiency of the oil palm seedling compared to their same system but in a larger size.


We aim to examine how season and temperature levels affect physical activity using a wearable device among patients scheduled to undergo surgical resection of lung cancer. Physical activity (PA) data from the wearable device were analyzed by seasons for 555 preoperative lung cancer patients from the CATCH-LUNG cohort study. The seasons were divided into spring, summer, autumn, and winter using the study enrollment date before surgery. The overall mean (SD) age was 61.1 (8.9) years, and the mean (SD) daily steps at each season were 11,438 (5922), 11,147 (5065), 10,404 (4403), and 8548 (4293), respectively. In the fully-adjusted models, patients in the winter season had 27.04% fewer daily steps  and 35.22% less time spent performing moderate to vigorous physical activity (MVPA) compared to patients in the spring. The proportion of participants with over 8000 steps and duration of MVPA were significantly lower in the winter than the spring. In particular, daily steps had a negative linear association with wind chill temperature in patients who lived in Seoul. In conclusion, PA was significantly lower in the winter and it was more robust in patients who had a low cardiorespiratory function. Lung cancer is the leading cause of cancer-related death worldwide, contributing to 1.6 million deaths annually . Both caCardiorespiratory fitness (CRF) and functional capacity are affected by physical activity (PA) . Numeroun = 2) and 63 patients who were excluded due to lack of Fitbit data (28 patients wore their Fitbit less than one day and 35 patients had either hardware or software failures of Fitbit). The final study sample included 555 patients. The study protocol was approved by the Institutional Review Board of Samsung Medical Center (no. 2015-11-025). Written informed consent was obtained from all participants.Patients with lung cancer in this study were selected from the Coordinate Approach to Cancer patients’ Health for Lung Cancer (CATCH-LUNG) cohort of preoperative lung cancer patients between March 2016 and October 2018 at the Samsung Medical Center in Seoul, Korea. Inclusion criteria for CATCH-LUNG cohort were (1) patients who were expected to undergo curative lung cancer surgery for suspected or histologically confirmed NSCLC, (2) patients who were able to walk and keep a normal life with the Eastern Cooperative Oncology Group Performance Status (ECOG PS ≤1), and (3) patients understood the purpose of this study and agreed to participate in the study. Exclusion criteria were (1) patients who had undergone neoadjuvant treatment before surgery, (2) patients free of NSCLC after pathological exams, (3) patients whose surgery was canceled, or (4) patients who withdrew consent before baseline data collection. Among patients who met these criteria, we furthermore excluded patients who had either pathologically confirmed stage IV cancer after surgery (https://data.kma.go.kr).The main exposure variable was the season, which was divided into spring (March to May), summer (June to August), autumn (September to November), and winter (December to February) using the study enrollment date before surgery. For preoperative patients living in the metropolitan Seoul area, the weather-related factor of wind chill temperature was obtained from the Korea Meteorological Administration , which was performed according to ATS guidelines . Each pa1), forced vital capacity (FVC), and DLco were obtained, and the percentage of predicted values (% predicted) for FEV1, FVC, and DLco were calculated using a representative Korean sample [Spirometry and DLco measurements were performed using a Vmax 22 respiratory analyzer  according to the American Thoracic Society/European Respiratory Society criteria ,19. Abson sample ,21 as a χ2 test, respectively.Continuous and categorical variables were compared among the seasons using analysis of variance (ANOVA) and the p-values based on Shapiro–Wilk and Shapiro–Francia tests for normality were <0.001), we used log-transformed daily number of steps and MVPA time as the outcomes. The average difference ) was estimated comparing patients enrolled in the summer, autumn, or winter to those patients enrolled in the spring.For the main analyses, we used linear regression to compare the daily number of steps and the moderate-to-vigorous physical activity (MVPA) time by season. Since steps per day and MVPA minutes are markedly right skewed , and any extra-pulmonary comorbidities (cardiovascular diseases or diabetes mellitus). In addition, we performed stratified analyses to evaluate differences in PA associated with the season in prespecified subgroups of age (<65 vs. ≥65 years) [Logistic regression was conducted to compare the odds of being physically active by season with adjustments made for age, sex, smoking status, FEV5 years)  and CRF 5 years) .n = 85) living in the Seoul metropolitan area because we considered the bias of area environment and topography in Korea. To find an association between weather and daily steps, we modeled wind chill temperature as a continuous variable using restricted cubic splines with knots at the 5th, 35th, 65th, and 95th percentiles of the sample distribution to provide a flexible estimate of the dose-response relationship between weather factors and daily steps.To determine factors leading to the differences in PA according to season, we conducted an additional analysis for patients .For all analyses, a n = 171), 32.1% (n = 178), 17.8% (n = 99), and 19.3% (n = 107) of the study subjects were collected in the spring, summer, autumn, and winter seasons, respectively. Although patients in the winter season were likely to be younger and have better pulmonary function than patients in other seasons, the clinical characteristics, including sex, BMI, smoking status, comorbidities, pathologic stage, and cardiorespiratory fitness, were not different across the seasons (The characteristics of 555 patients are described in  seasons .The mean (SD) daily steps were 11,438 (5922), 11,147 (5065), 10,404 (4403), and 8548 (4293) in patients who participated in this study in the spring, summer, autumn, and winter seasons, respectively. The proportion of patients who had 8000 or more steps per day was 71%, 72%, 71%, and 54% in participants who received surgery in the spring, summer, autumn, and winter seasons, respectively .In the fully-adjusted models, patients in the winter season had a significantly lower number of daily steps, with a low of 27.04%  compared to the daily steps of patients in the spring season. In comparing the mean (SD) MVPA time, patients in the winter season had the lowest MVPA among subjects  min/d; summer, 58.5 (46.4) min/d; autumn, 51.0 (35.6) min/d; and winter, 35.0 (36.3) min/d). In the fully-adjusted models, compared to patients in the spring season, the MVPA time was significantly shorter by 35.22%  for patients in the winter season. The number of steps and duration of MVPA were significantly lower in the winter season compared to spring season irrespective of age and 6MWD .In the fully-adjusted models, the OR for 8000 or more steps per day was 0.46  for patients in the winter compared to those in the spring. The proportion of patients who had 60 min or more MVPA per day was also similar . In the fully-adjusted models, the OR for MVPA ≥ 60 min/day was 0.52  for patients in the winter compared to those in the spring. In particular, the OR for low CRF (<500 m) was 0.30  for patients in the winter compared to those in the spring .In the spline regression models, the relationship between wind chill temperature and daily steps was linear below 25° wind chill temperature, with lower daily steps corresponding to colder temperatures . The assWe found that preoperative PA was significantly lower in the winter season compared to other seasons, irrespective of age and CRF. In particular, the low MVPA in the winter season was more robust in patients who had low CRF, but the effect was not statistically significant. In terms of weather factors, wind chill temperature was inversely associated with PA. These results demonstrate that the PA of preoperative lung cancer patients is significantly affected by the season and temperature levels.Our study showed that daily step was lower by 27% in the winter season compared with the spring season. These findings are consistent with previous studies that showed the association between daily PA and the season ,29,30. TWe found that a few patients achieving MVPA ≥ 60 min/day were more robust in patients with low CRF (≤500 m of 6MWD) compared to those with high CRF (>500 m of 6MWD). Lower exercise tolerance assessed through the 6MWD is associated with poorer postoperative outcomes after lung resection . HoweverHowever, seasons are a crude measure when it comes to understanding the effects of weather on PA . PreviouThere are several limitations to this study. Firstly, this was a cross-sectional study and we were not able to observe the change of PA of the same patient group in different seasons. In addition, due to enrollment periods, a limited number of patients were observed in the winter season. These factors limited our ability to observe the magnitude of seasonal variation in PA among patients. Despite these limitations, our study indicates little variability in PA by season. In fact, patients in the winter season were younger and had better lung function than patients in other season and we still see the different levels of PA depending on season. Secondly, patients who were motivated to perform PA might be more likely to participate in the study. The mean daily step figures were higher in this study compared to data reported in earlier studies . This miIn this study, we found that season and temperature levels affect PA among preoperative lung cancer patients. Patients were much less physically active in the winter season than other seasons and patients in the winter season had lower cardiorespiratory function. Health professionals need to be aware of these seasonal differences and recommend indoor physical activities that preoperative patients with lung cancer can do in winter.


Severe coronavirus disease-19 (COVID-19) presents with progressive dyspnea, which results from acute lung inflammatory edema leading to hypoxia. As with other infectious diseases that affect the respiratory tract, asthma has been cited as a potential risk factor for severe COVID-19. However, conflicting results have been published over the last few months and the putative association between these two diseases is still unproven.Here, we systematically reviewed all reports on COVID-19 published since its emergence in December 2019 to June 30, 2020, looking into the description of asthma as a premorbid condition, which could indicate its potential involvement in disease progression.We found 372 articles describing the underlying diseases of 161,271 patients diagnosed with COVID-19. Asthma was reported as a premorbid condition in only 2623 patients accounting for 1.6% of all patients.As the global prevalence of asthma is 4.4%, we conclude that either asthma is not a premorbid condition that contributes to the development of COVID-19 or clinicians and researchers are not accurately describing the premorbidities in COVID-19 patients. Severely affected patients present fever, dry cough, dyspnea, and fatigue, which are commonly associated with the development of pneumonia and acute respiratory distress syndrome (ARDS) [COVID-19 was first reported in December, 2019 in Wuhan, China, and rapidly spread across the globe [e (ARDS) . As withe (ARDS) –8. This e (ARDS) . HoweverHere, we systematically reviewed all studies published on COVID-19 since its emergence in December 2019 to June 30, 2020, looking into the description of asthma as a premorbid condition and its putative association with severe progression of the disease. We show that out of 161,271 patients diagnosed with COVID-19 and having their premorbid conditions described, only 1.6% were reported as previously diagnosed with asthma.COVID-19  or nCov or novel coronavirus or Sars-Cov-2 in the title and clinical characteristics or asthma anywhere in the text. Three authors, EM, EPA, and LAV, resolved eventual discrepancies by discussion and adjudication.This is a systematic review of the diagnosis of asthma as a premorbid condition in patients with COVID-19. The report was organized according to the Preferred Reporting Items for Systematic Reviews . Two autWe found 1069 articles that met the initial inclusion search criteria. All articles were assessed by authors and 598 were excluded . Its recurrent nature leads to frequent hospitalizations and high mortality, ranging from 2 to 4/100,000 [Asthma is a highly prevalent, chronic, non-communicable disease that affects up to 4.4% of the world’s population  and could suggest that having asthma as a premorbid condition either represents no risk for COVID-19 or could be a protective factor against the development of the disease. However, there are some aspects that should be considered as potentially impactful for the findings herein reported. First, the prevalence of asthma varies across the globe, ranging from 21% in Australia to less than 2% in China, Kazakhstan and Vietnam [www.who.org). Thus, the geographical origin of the studies could have influenced the results. However, as the studies included in this systematic review were mostly originated from countries presenting a wide range of prevalences for both asthma and the main comorbidities for COVID-19, we believe this factor plays a minor role in the reported findings.Here, we evaluated all studies on COVID-19 published since its emergence up to June 30, 2020. We showed that asthma was described as a premorbid condition in only 1.6% of all patients. These numbers are far less than expected considering the prevalence of asthma in the world , rendering asthma patients protected from the infection –30. ThisThe main weaknesses of this systematic review rely on the facts that we included publications covering the initial 6 months of pandemics and as new data is published on a daily basis, some changes in the frequency of asthma could appear; moreover, readers should keep in mind that some reports show that in certain pocket populations, asthma could be an important comorbidity for COVID-19 . The reaThus, as for the data analyzed in this systematic review, asthma does not seem to be an important premorbid condition in COVID-19 patients; or, conversely, it could be a protective factor, as previously proposed . The finAdditional file 1: Table 1. Excluded articles. Table 2. Included articles.


During the COVID-19 pandemic, healthcare workers (HCW) have been exposed to multiple psychosocial stressors. Resilience might protect employees from the negative consequences of chronic stress. The aim of this study was to explore the mediating role of resilience in the relationship between depression and burnout . A cross-sectional study was performed using an online questionnaire distributed via social networks. A survey was conducted comprising standardized measures of resilience , depression , and burnout . A total of 2008 subjects completed the survey, and a hierarchical regression model was estimated for each burnout dimension. The results revealed that depression had not only a directed effect on personal, work- and client-related burnout, but also an indirect small effect on it through resilience. Psychological resilience played a partial mediating role between depression and all burnout dimensions. This partial mediation suggests that there may be other possible variables  that further explain the associations. The COVID-19 pandemic is a global public health emergency with tremendous consequences for people’s lives and their mental health. On 2 March 2020, Portugal announced the first confirmed case of SARS-CoV-2. On 9 May 2020, 26,715 cases of COVID-19 were recorded. One month later, the number of cases was confirmed as 35,910 with more than 1500 deaths . If prolBurnout and psychological distress seem to have been some of the immediate effects of the pandemic on health professionals ,4,7,8. BIn this pandemic scenario, fear of COVID-19 contagion seems to be an exacerbator of distress and has been found to be associated with negative mental health outcomes ,12,13. IA cross-sectional web survey  of New YAccording to Luceño-Moreno et al. , in SpaiAnother study developed in China shows that about half (50.4%) of the HCW reported symptoms of depression .Weilenmann et al. , in SwitBurnout can affect health, leading to the development of physical and psychosomatic symptomatology and depression . BurnoutIt is also worth noting that not all individuals exposed to very intense crisis situations suffer from mood disorders, with resilience being vital as a protective variable ,19,20,21The existing literature considers that psychological resilience represents an adaptive quality that allows the person to grow in consequence of experiencing traumatic situations and high stress ,25. StudWest et al.  examinedResilience seems to have a mediation role in some psychological variables . Little Thus, understanding resilience is important as a means to developing interventions to prevent/treat mental disorders and promote mental health. The issue of resilience and the possible benefits of resilience training are particularly relevant in professional groups who are exposed to various sources of stress ,37. Considering the available evidence that psychological resilience might protect workers from the negative consequences of chronic stress e.g., ,25,37, t® Forms platform. Subjects who did not develop their professional activity in the health field and who answered all items of the Scales were excluded. As inclusion criteria, all subjects working in Portugal during the data collection period were included. Ethical procedures according to the Declaration of Helsinki were accomplished via analysis and approval of the study by an independent Ethical Committee  (Ref 184/2020 on 7 May 2020).This was a cross-sectional quantitative study directed to HCW living in Portugal. Data was collected through a web survey disseminated on social networks using and spread through the snowball sampling technique. The data collection period spanned from 9 May to 8 June 2020. In Portugal, during this period, national calamity was declared, and the state of national emergency was followed by a relieving of lockdown measures (between 18 March and 2 May). A questionnaire was made available to participants via a link which was spread by professional organizations  and healthcare institutions by e-mail and social networks. The questions were answered online through the GoogleA total of 2008 HCW completed the questionnaire. There was a marked predominance of females . This distribution of participants may be due to the high level of feminization of health professionals in Portugal. The global feminization rate in Health is 76% . The aveThe participants of this study were 707 (35.2%) allied health professionals , 511 (25.4%) physicians, 409 (20.4%) nurses, 88 (4.4%) pharmacists, 83 (4.1%) psychologists, 72 (3.6%) nutritionists, 29 (1.4%) healthcare assistants, and 21 (1%) workers in allied areas. Of all of the participants, 485 (24.2%) were in primary healthcare, 383 (19.1%) in inpatient areas, 247 (12.3%) in emergency services, 167 (8.3%) were in COVID-19 inpatient areas exclusively, and 157 (7.8%) worked in high-dependency units (intermediate and intensive care). Amongst the participants, 524 (26.1%) revealed having health problems such as chronic respiratory disease  and a compromised immune system . A total of 319 (15.9%) subjects were caring for older people or with disabilities. In The questionnaire comprised two parts: epidemiology , psychological resilience, psychological distress , and burnout. The Resilience Scale  was used® Statistics  and Jamovi software . Categorical variables were described by absolute and relative frequencies. Quantitative normally distributed variables were described by the mean and the respective standard deviation (SD). Quantitative non-normally distributed variables were described by the median (Mdn) and the respective interquartile interval . The normality of distributions was verified by observation of the respective histograms. For each outcome , a separated multiple linear regression was performed. To decide which independent variables to include in each multiple regression, simple linear regressions were performed with each of the following variables: sex, marital status , children , educational level , co-living , caregiver (no/yes), lives with a person at risk for COVID-19 infection (no/yes), death of relative or friend during the pandemic period (no/yes), years of professional experience , salary reduction (no/yes), frontline working position (no/yes), diagnosed health problem (no/yes), COVID-19 tested  and direct contact with infected people (no/yes). All variables that correlated with the outcomes at p ≤ 0.20 in a simple regression were included in the multiple linear regressions. Only the significant variables were maintained in the final multiple models. A hierarchical regression model was estimated to examine the mediating role of resilience in the relationship between depression and each burnout dimension: personal burnout, work-related burnout, and client-related burnout. The following requirements for such analysis were verified: a significant correlation between depression (independent variable) and burnout (dependent variable); a significant correlation between depression and resilience (the mediator) and between resilience and burnout. Additionally, the effect of depression on burnout should shrink  or become statistically insignificant (full mediator) after the inclusion of resilience in the model. Standardized estimates (β), F statistics, determination coefficient (R2), and R2-changes (ऴR2) for each step were provided. Multicollinearity was checked through tolerances and variance inflation factors ranges. Finally, the Sobel test was pursued to assess the mediation effect.Data analysis was performed using SPSSp ≤ 0.05 were considered significant. Values of In general, participants showed a moderate level (50.8%) or high level of psychological resilience (27.8%), normal levels for depression (70.6%), high levels of work, personal and client-related burnout, 53.1%, 52.5%, 35.4%, respectively. p < 0.001), and a negative association between personal burnout and resilience, accounting for an increase of 1.5% in the explained variance .The mediating role of resilience in the relationship between depression and personal burnout (outcome) was explored through hierarchical linear regression analyses and the results are demonstrated in p < 0.001), resilience was found to play a partial mediating role in the association between depression and personal burnout  reduced from 0.530 to 0.480 after the inclusion of resilience in the model , and a negative association between work-related burnout and resilience, accounting for an increase of 1.2% on the explained variance . The mediating role of resilience in the relationship between depression and work-related burnout (outcome) was explored through hierarchical linear regression analyses and the results are demonstrated in p < 0.001). Multicollinearity was not problematic since tolerance range was 0.909–0.992 and variance inflation factors varied between 1.01 and 1.10.Resilience was found to play a partial mediating role in the association between depression and work-related burnout  since β p < 0.001), and a negative association between resilience and client-related burnout, accounting for an increase of 1.2% in the explained burnout variance . The results from the hierarchical linear regression model for exploring the mediating role of resilience in the relationship between depression and client-related burnout (outcome) are demonstrated in p < 0.001). Once again, multicollinearity was not problematic since tolerance range was 0.918–0.998 and variance inflation factors varied between 1.00 and 1.09.Resilience was found to play a partial mediating role in the association between depression and client-related burnout  since β The aim of the present study was to analyze the potential mediating role of psychological resilience in the impact of depression on burnout among Portuguese HCW. Psychological resilience means that individuals can adapt and respond to difficulties, traumas, tragedies, and adversity . In thisThe results show that more than half of HCW presented high levels of fatigue and exhaustion related to work 53.1%), personal (52.5%), and client-related burnout (35.4%). These results are substantially higher than those found in the study developed in India with a sample of 2026 HCW , where t3.1%, perOur data suggests that HCW have a moderate or high level of psychological resilience, which echoes recent findings in the literature ,45,47. AThere is little research which has investigated the mediating role of resilience between depression and burnout. Moreover, in recent times the discussion has focused on whether depression and burnout are equal  or diffeThe mediational models obtained show that resilience seems to partially mediate the relationships amongst depression and all dimensions of burnout . Depression had not only a directed effect on personal, work-, and client-related burnout, but also an indirect small effect on it through resilience. It should be noted that this partial mediating effect may have been detected by the large sample size, since it produces a small increase in the determination coefficient. The HCW who scored higher on depression had lower resilience, resulting in higher levels of three dimensions of burnout, while those who scored low on depression had higher resilience, contributing to lower levels of personal, client-, and work-related burnout. The partial mediation suggests that there may be other possible variables  which fBurnout is a response to stressful events ,10,28 anIn burnout, it should be noted that over half of these professionals have high scores in work-related and personal burnout, but low in client-related burnout. Despite the fatigue and exhaustion, they felt inherent in overwork and multiple other stressors, with direct repercussions on personal and family life in which, their supportive and caring performance was not perceived in the same way. This result may be due to society’s broad recognition of health professionals, their perception of value, and self-recognition. On the other hand, training may have helped to achieve this result. Recent research has indicated that, during the COVID-19 outbreak, a significant percentage of HCW have high levels of emotional exhaustion, low in depersonalization and very high in personal accomplishment . Exposure to COVID-19 patients had significant effects while the independent variable on all burnout dimensions. This result indicates that HCW who were in contact with infected patients were more likely to experience personal burnout, work-related burnout, and client-related burnout. This result highlights the need for organizations to develop protective strategies ,21,22 inOur study had the following limitations. Firstly, the study is based on a web-based survey, disseminated through email and social networks, which might have been affected by self-selection bias. For example, we can hypothesize that HCW who were most likely to respond to the survey were those with digital literacy or those who were more aware of the problems caused by burnout. Secondly, this study was a cross-sectional investigation, so interpretation of the results of mediation results on cross-sectional data must proceed with caution. Thirdly, the study was carried out during a specific pandemic period, meaning that it is necessary to employ a longitudinal design which examines the long-term effects of the pandemic in HCW and the level of psychological resilience. Finally, this study suggests that there may be other potential variables which elucidate the associations between depression and burnout. In this sense, it would be useful to consider other internal and external variables in future research. HCW living in Portugal experienced a high prevalence of burnout. After adjusting independent variables , depression was positively associated with burnout dimensions and negatively associated with resilience. Furthermore, resilience could partially mediate the relationship between depression and dimensions of burnout. Considering that a second wave of infections is already happening and that there is a rise in workload in a context of doubt and insecurity, it is expected that burnout and depression might worsen. The solution will require increased funding for mental health, particularly for professionals who report symptoms of psychological distress .