High Adverse Effects Research Articles

Optimizing Individualized Antimicrobial Dosing in Pediatric Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Therapeutic drug monitoring (TDM) and target concentration intervention (TCI) represent significant advancements in individualized medicine, aiming to tailor dosages based on patient-specific characteristics. These approaches account for intra- and inter-individual physiological and clinical variability, with the goal of improving target attainment and clinical remission while reducing treatment failure and adverse effects. The objective is to assess and enhance the current body of randomized controlled trials (RCTs) that have investigated alternative personalized dosing strategies, such as TDM and TCI, in terms of their efficacy and safety for individualized antimicrobial dosing in pediatric populations. Only studies that compared different dosing regimens and reported plasma concentrations were included in the analysis. Databases such as MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched until January 3rd, 2024. Only published, peer-reviewed RCTs were considered for inclusion. The study focused on human subjects aged < 18 years who were receiving an antimicrobial drug. The interventions compared experimental dosing versus standard dosing with TDM or TCI. The risk of bias was assessed using version 2 of the Cochrane risk-of-bias tool for randomized trials. The primary outcome was the attainment of target concentrations, while secondary outcomes included adverse effects, clinical remission, and treatment failure. Data synthesis was performed using the restricted maximum likelihood method, and the risk ratio (RR) was used as the measure of effect size. Only 11 TDM-based RCTs were included in the study [experimental vs standard doses: 592 (51.3%) patients vs 563 (48.7%) patients]. Experimental dose was significantly associated with improvement in target attainment (RR 1.2587, OR 1.0717-1.4786; p=0.0051). However, experimental antimicrobial dose optimization was non-significantly associated with a numerical decrease in treatment failure (RR 0.8966, OR 0.7749-1.0374; p=0.1424). In addition, it was not significant associated with higher adverse effects [RR 1.3408, odds ratio (OR) 0.1783-10.0825; p=0.7757] and clinical remission rates (RR 4.0589, OR 0.2494-66.0558; p=0.3250). This meta-analysis showed that only target attainment using TDM was significantly improved in pediatric patients treated with experimental doses of antimicrobials compared to standard doses. Larger TCI-focused RCTs are needed to significantly improve treatment failure, adverse effects, and clinical remission.

Efficacy and safety of first-line anti-tuberculosis drugs combined with Linezolid for the treatment of pediatric tuberculous meningitis in real-word practice

Objective: To evaluate the efficacy and safety of first-line anti-tuberculosis (TB) drugs combined with linezolid in treatment of children with tuberculous meningitis (TBM). Methods: A retrospective cohort study design was performed. Eight-nine Children diagnosed as TBM during January 1st 2016 and December 31st 2023 in Department of Infectious Disease, Children's Hospital of Chongqing Medical University were enrolled in the study. According to different treatment regimens, children were divided into a group of first-line anti-tuberculous drugs (isoniazid, rifampicin, pyrazinamide, ethambutol (HRZE)) and a group of HRZE and linezolid combination (HRZEL). The efficacy and safety of the 2 regimens were compared and the relationship between linezolid drug concentration and adverse reactions were analyzed. Comparisons between groups were performed using χ2 test and Mann-Whitney U test. Results: The 89 children with TBM included 53 males and 36 females with an onset age of 4.6 (1.4, 9.6) years. There were 27 cases in the HZREL group and 62 cases in the HRZE group. Before treatment, positive rate of interferon-gamma release assays (IGRA) in HRZEL group was lower than that in HRZE group (64% (16/25) vs.92% (55/60), χ2=9.82, P<0.05), but protein level of cerebrospinal fluid (CSF) was higher than that in HRZE group (1.2 (1.0, 2.0) vs.0.8 (0.4,1.4) g/L, Z=0.32, P<0.05). By the end of the intensive phase, there were no significant differences of rates of CSF improvement and etiology negativity between HRZEL group and HRZE group (both P>0.05).The 44 TBM children with high CSF protein (>1 g/L) included 25 males and 19 females with an onset age of 6.7 (3.0, 11.8) years. There were 21 cases in the HZREL group and 23 cases in the HRZE group accordingly. Before treatment, there were no significant differences of positive rate of IGRA test and CSF protein level between the 2 groups (62% (13/21) vs. 87% (20/23), 1.7 (1.1, 2.2) vs. 1.5 (1.2, 1.9) g/L, χ2=3.67, Z=0.23, both P>0.05). There were no significant differences in CSF indicators, etiology negativity or imaging remission between the two groups by the end of intensive phase (all P>0.05). Higher frequencies of granulocytopenia, gastrointestinal symptoms as well as withdrawal or change of drugs were found in HRZEL group when compared to those in HRZE group (44% (12/27) vs. 19% (12/62), 7% (2/27) vs. 0, 33% (9/27) vs. 3% (2/62), χ2=6.01, 4.70, 15.74, all P<0.05). Conclusions: The efficacy of HRZEL regimen is similar to conventional HRZE regimen in children with TBM, but with higher adverse effect. Prudentially evaluating the pros and cons of linezolid in the usage of drug-susceptible TB and carefully monitoring of linezolid associated adverse effects is suggested.

Lithofacies assemblage and effects on diagenesis in lacustrine tight sandstone reservoirs: Samples from Upper Triassic Yanchang Formation, Ordos Basin, China

Lacustrine basins are rich in unconventional oil and gas resources and the heterogeneity of matrix reservoir quality seriously affects its development. Previous studies have recognized that diagenesis is the key factor affecting the heterogeneity of matrix reservoir quality, but diagenesis controlled by lithofacies assemblages is poorly studied. In this study, tight sandstones in the Triassic (Ladinian-Carnian) Chang 7 Member of Ordos Basin were taken as examples. Lithofacies, lithofacies assemblages, diagenesis evolution and distribution were investigated by casting thin section analysis, scanning electron microscopy (SEM), X-ray diffraction (XRD), fluid inclusion and carbon-oxygen isotope. The results indicate that eight lithofacies assemblages in Chang 7 exhibit variations in lithofacies, sand-mud ratio and grain size rhythm, controlling the distribution and intensity of diagenesis. Variations in average proportion of lithofacies assemblages are linked to lake level cycles. Compared to cementation, the mechanical compaction has a higher adverse effect on primary porosity of tight sandstones in Chang 7. Siltstone lithofacies show stronger compaction and cementation (mainly clay cementation), whereas fine sandstone lithofacies exhibit stronger dissolution, especially FSpc (fine sandstone with parallel or cross-bedding). Modest proportions of illite (<4%) and chlorite (<1.5%) in fine sandstones tend to form clay coatings, resisting compaction and preserving more porosity. Conversely, abundant pore-filling illite (>4%) and chlorite (>1.5%) result in a noticeable decline in porosity. Particle size and sorting affect reservoir quality by controlling compaction strength. The origin of carbonate cement in sandstones is closely related to mud-rich lithofacies within lithofacies assemblages. Carbonate cementation preferentially occurs in fine sandstones within 0.4 m from the sand-mud interface and the thickness of adjacent mud-rich lithofacies is greater than 0.1 m. Interfaces between fine sandstones serve as fluid migration pathways and bidirectional erosion, facilitated by high porosity and feldspar content. In contrast, the clay-rich matrix in siltstones acts as a barrier hindering fluid migration, creating unidirectional erosion in fine sandstones near the interfaces between siltstones and fine sandstones. Ultimately, five evolution processes linking diagenesis with lithofacies assemblages are summarized, highlighting the differential reservoir quality. This study contributes to understanding the mechanism behind diagenetic variations in tight sandstones and the reservoir evaluation. Consequently, it offers geological reference for the development of unconventional oil and gas resources in comparable lacustrine basins.

A Comprehensive Review of Sulfonamide Hypersensitivity: Implications for Clinical Practice.

Sulfonamides, which are drugs commonly prescribed in hospital and outpatient settings, have historically been associated with a high incidence of hypersensitivity reactions. It is believed that there is an increased risk of cross-reactions with other drugs that contain this functional group in their structure. However, it has not been conclusively established that the sulfonamide group is the sole cause of hypersensitivity reactions, as non-antibiotic sulfonamides do not share the same accessory groups with antibiotic sulfonamides. Therefore, cross-reactivity between different types of sulfonamides and sulfonamide-type antibiotics is not clearly demonstrated, and allergic reactions may involve other mechanisms. Misinformation about this topic can lead to inappropriate use of alternative antibiotics with lower efficacy or higher adverse effects, contributing to antibiotic resistance. It is crucial to individualize and monitor patients with a history of allergies to sulfonamide-type antibiotics when introducing a new drug containing sulfa and manage any adverse reactions promptly. Desensitization protocols may be a viable option for patients who specifically benefit from these antibiotics, particularly those who are immunosuppressed. This article provides a descriptive bibliographic review to update information on sulfa allergy, its prevalence, management, and recommendations to prevent such reactions and optimize pharmacotherapy, without underusing these drugs.

Histopathological Analysis of Hexavalent Chromium Toxicity to Ovary and Testis of Freshwater Food Fish, Channa punctatus (Bloch. 1793)

A major issue nowadays is aquatic contamination by heavy metals like Chromium as a result of industrial, agricultural and domestic activities and cause threat to the aquatic ecosystem. This study's objective was to evaluate the toxicological effects of chromium (VI) in freshwater food fish, Channa punctatus. For the experiment, a medium-sized fish (10 ± 2 cm, 30 ± 5 g) was collected from local aquatic habitat and acclimatised in a lab under controlled conditions. There were one control and three exposed groups having different sublethal concentrations of chromium (LC50/5 = 15.378 mg/l, LC50/10 = 7.689 mg/l, and LC50/20 = 3.844 mg/l). Fish sacrificed to create slides after the desired duration. Compared to control, fish exposed to different subletal concentrations showed substantial alterations in their gonads. The highest adverse effects were seen in the ovary and testes in group 4 (LC50/5) compared to the lower in group 2 (LC50/20) in contrast to the control (group 1), Large intrafollicular gaps and nuclear membrane rupture in stage IInd oocytes were seen in the ovary, whereas intralobular edoema, disruption of the germinal epithelium, and severe vacuolization were recorded in the testes. According to the findings of the current research, chromium (VI) has a negative impact on fish reproductive tissue and disturbs ecological balances.

Sustainable wind energy planning through ecosystem service impact valuation and exergy: A study case in south-central Chile

Wind energy has great potential to drive Chile's energy sector towards a more sustainable model; however, it could induce landscape changes impacting ecosystem services. Accordingly, this study aimed to identify the best areas for wind energy development in Biobío and Ñuble regions, by integrating metrics from suitability analysis, ecosystem service valuation and exergy. The trade-offs between ecosystem services and wind electricity generation were assessed through biophysical indicators. Then, a new indicator based on ecosystem services impacts and exergy concept was developed to determine the most sustainable sites for wind energy development. Results showed that deploying wind energy could have the highest adverse effects on erosion regulation services, with an increase of 40%–50% in soil loss for Ñuble and Biobío. Moreover, the crop and timber provision were also reduced by 10%, while water-related services were favored by an increment of 10% in water savings. The proposed indicator took negative values in all suitable zones under analysis (−25 to −307 GJex/GWh), indicating that ecosystem services losses exceeded gains. Results suggest that seven zones are potential sites for wind energy development based on their impacts which were up to −39 GJex/GWh. This work provides evidence for promoting sustainable wind energy planning by locating the projects in zones with the lowest detrimental ecosystem services impacts.

Safety and efficacy of PD-1 and PD-L1 inhibitors in relapsed and refractory Hodgkin's lymphoma: a systematic review and meta-analysis of 20 prospective studies

ABSTRACTBackground: Inhibitors of programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) have been used in the treatment of relapsed and refractory Hodgkin's lymphoma (R/R HL) recently. To further understand the safety and efficacy of PD-1/PD-L1 inhibitors in R/R HL, we conducted this meta-analysis.Methods: Databases and the Clinical Registration Platforms have been systematically searched for related studies by March 2022. For safety analysis, the incidence and exhibition of any grade and grade 3 or higher adverse effects (AEs) were evaluated. Besides, severe AEs (SAEs), treatment-related deaths, and AEs leading to treatment discontinuation were summarized. The overall response rate (ORR), complete response (CR) rate, partial response (PR) rate, progression-free survival (PFS), overall survival (OS), and duration of response (DOR) were calculated for efficacy analysis. All processes were implemented mainly through the package Meta and MetaSurv of software R 4.1.2.Results: Overall 20 studies and 1440 patients were enrolled. The pooled incidence of any grade and grade 3 or higher AEs were 92% and 26%, respectively. The pooled ORR, CR rate and PR rate were 79%, 44% and 34%, respectively. The most common AEs were neuropathy (29%), nausea (27%), pyrexia (26%), and leukopenia (25%), and the most common grade 3 or higher AEs included leukopenia (10%), infusion reaction (8%), weight gain (3%), and neutropenia (2.7%). In survival analysis, pembrolizumab monotherapy appeared to perform better compared to nivolumab monotherapy.Conclusions: PD-1/PD-L1 inhibitors show promising efficacy and tolerable AEs in the treatment of R/R HL.

Optimal sequential therapy using tyrosine kinase inhibitors as the first-line treatment in patients with metastatic renal cell carcinoma: A nationwide multicenter study

ObjectiveThe purpose of the study was to identify the best sequence of therapy beginning with a tyrosine kinase inhibitor (TKI) as the first-line therapy for patients with metastatic renal cell carcinoma (mRCC) in terms of overall survival (OS), progression-free survival (PFS), and rates of discontinuation and adverse effects during the treatment period. MethodsThis is a retrospective, nationwide multicenter study of patients with mRCC after diagnosis at 10 different tertiary medical centers in Korea from January 1992 to December 2017. We focused on patients at either “favorable” or “intermediate” risk according to the International mRCC Database Consortium criteria, and they were followed up (median 335 days). Finally, a total of 1409 patients were selected as the study population. We generated a Cox proportional hazard model adjusted for covariates, and the different therapy schemes were statistically tested in terms of OS as well as PFS. In addition, frequencies of discontinuation and adverse events were compared among the therapy schemes. ResultsOf the primary patterns of treatment sequences (24 sequences), “sunitinib–pazopanib” and “sunitinib–everolimus–immunotherapy” showed the most beneficial results in both OS and PFS with significantly lower hazards than “sunitinib”, which is the most commonly treated agent in Korea. Considering that the “TKI–TKI” structure showed relatively higher discontinuation rates with higher adverse effects, the overall beneficial sequence would be “sunitinib–everolimus–immunotherapy”. ConclusionAmong several sequential therapy starting with TKIs, “sunitinib–everolimus– immunotherapy” was found to be the best scheme for mRCC patients with “favorable” or “intermediate” risks.

The synergistic effect of retinyl propionate and hydroxypinacolone retinoate on skin aging.

Aging is responsible for the majority of skin and soft tissue remolding in humans. Retinol and its derivatives or retinoids effectively intervene skin aging process. Nevertheless, retinoids usually induce skin intolerance, especially among the Chinese, and thus, their application to prevent skin aging is yet to be well accepted. The study of optimal composition and concentration of retinoids is necessary to offer strong antiaging efficacies with minimum irritations. Therefore, a better understanding of retinol and its derivatives is acutely needed to develop strategies to combat skin aging. In this study, we aimed to determine the optimal ratio of two retinol derivatives-hydroxypinacolone retinoate (HPR) and retinyl propionate (RP) in terms of dermal remodeling and skin aging prevention-and to investigate their synergistic antiaging effects both in vitro and in vivo. An in vitro human foreskin fibroblast (HFF-1) cell model was established to evaluate the cell viability of HPR and/or RP treatment. In addition, the antiaging and retinol receptor genes expressions in HFF-1 cells cotreated with HPR and RP were quantified. The in vivo adverse reaction evaluation of skincare serums containing various levels of retinol or the optimal HPR and RP combination termed Gravi-A was performed by 24 h patch tests in 33 subjects prior to the clinical research. Last but not the least, clinical research with 42 Chinese urban women was conducted to assess the in vivo antiaging efficacy of the skincare serum containing this optimal retinoid combination. The combination of HPR and RP at the weight ratio of 5:9 was shown to achieve the optimal in vitro antiaging performance. Coadministration of 5μg/mL HPR and 9μg/mL RP to HFF-1 cells promoted their proliferation at 24 h and synergistically enhanced the expressions of type IV collagen, CRBP-I, and RARB genes. In addition, the skincare serum containing HPR and RP combination at 5:9 weight ratio demonstrated superior in vivo anti-wrinkle and skin elasticity improvement benefits without any adverse reactions, while retinol in the same concentration exerted much higher adverse effect. Skin wrinkles, skin smoothness, TEWL, skin elasticity R2 and R5 were improved by 8.3%, 11.9%, 25.7%, 14.5%, and 22.6%, respectively, after 8-week use. Our results indicated the advanced antiaging effect of HPR and RP combination both in vitro and in vivo. In addition, little adverse effect was observed in this study, in comparison with retinol. This combination named as Gravi-A is a potential therapeutic strategy to prevent skin aging, especially for Chinese women.

Yttrium-90 Radioembolization for Liver-Dominant Metastatic Prostate Cancer: A Case Series

Transarterial radioembolization (TARE) with yttrium-90 glass microspheres is widely used to treat primary and secondary malignancies in the liver. However, the safety and efficacy of TARE in patients with liver-dominant metastatic castration-resistant prostate cancer (mCRPC) is unknown. A proof-of-concept, retrospective analysis of 7 consecutive patients with liver-dominant mCRPC who were treated with TARE was performed. The median overall survival was 27.2, 32.1, and 108.1 months from the time of TARE, the diagnosis of liver metastases, and initial cancer diagnosis, respectively. The median liver progression-free survival was 7.3 months. No grade 3 or higher adverse effects were noted. TARE was found to be a safe and effective tool for treating patients with liver-dominant mCRPC in this limited cohort.

Efficacy of adjuvant treatment for fracture nonunion/delayed union: a network meta-analysis of randomized controlled trials

BackgroundFracture nonunion/delayed union seriously affects physical and mental health and quality of life. The aim of this study was to evaluate the relative efficacy of different adjuvant treatments for nonunion/delayed union by network meta-analysis.MethodsA comprehensive search was performed to identify randomized controlled trials (RCTs) evaluating adjuvant treatment in the management of nonunion/delayed union. A network meta-analysis reporting on healing rate, healing time, and adverse effect (AE) outcomes was conducted to assess and compare different interventions.ResultsThirty studies were included in the analysis. For the healing rate outcome, bone marrow aspirate (BMA) + autologous cancellous bone (ACB) was found to be significantly better than ACB alone (odds ratio: 0.12; 95% confidence interval: 0.03, 0.59). In the ranking results, BMA+ platelet-rich plasma (PRP) (96%), BMA + ACB (90%), and BMA alone (82%) showed relative advantages in the healing rate. Low-intensity pulsed ultrasonography (LIUS) intervention significantly shortened the healing time compared with ACB (SMD: -9.26; 95% CI: − 14.64, − 3.87). LIUS (100%), BMA + PRP (74%), and bone morphogenetic proteins (BMPs) (69%) have relative advantages. Compared with the control, electromagnetic field (EMF) (OR: 13.21; 95% CI: 1.58, 110.40) and extracorporeal shock wave (ESWT) (OR: 4.90; 95% CI: 1.38, 17.43) had a higher AE risk.ConclusionsAmong the current intervention strategies, BMA in combination with PRP and ACB can improve the healing rate of nonunion/delayed union. LIUS can significantly shorten the healing time. EMF and ESWT may have a high risk of AE. However, large-scale, well-designed studies are still needed to confirm the results.Trial registrationRetrospectively registered.

Comparison of Topical Silymarin with Hydroquinone in the Treatment of Melasma

Objective: To compare the efficacy and safety of topical silymarin 0.7% with topical hydroquinone 4% in the treatment of melasma.&#x0D; Place and Duration: This Randomized Controlled Trial was conducted at dermatology OPD of Akbar Niazi Teaching Hospital, Bara Kahu, Islamabad, in a period of one year from April 2020 to April 2021.&#x0D; Patients and Methods: Female patients having melasma were included in the study. The severity of melasma was assessed using MASI score. Group A was treated with silymarin 0.7% cream and group B was treated with topical hydroquinone 4% cream. Treatment was given for 3 months and was followed up for the next 3 months to observe relapse. Clinical efficacy was assessed in terms of percent reduction in MASI score from baseline.&#x0D; Results: The mean age in group A (Silymarin 0.7%) was 35.13 ± 3.87 and in group B (Hydroquinone 4%) was 34.16 ± 3.90. Epidermal type of melasma was most common (76.8% vs 62.5%) in both groups. There was no significant (p-value &lt; 0.05) difference between both groups after one and two months treatment but mean MASI score of Hydroquinone 4% group (10.59 ± 5.74) become significantly (p-value &lt; 0.05) less than Silymarin 0.7% group (8.20 ± 4.41) after 3 months. Similar (p-value &gt; 0.05) therapeutic response was observed after one and two months treatment but it become significantly better in Hydroquinone 4% group after three months treatment. Significantly, (P-value &lt; 0.05) higher adverse effects were detected in patients treated with hydroquinone. There was no difference (P-value &gt; 0.05) in recurrence rate and patients satisfaction between both groups.&#x0D; Conclusion: topical silymarin has equal efficacy for the treatment of melasma with comparatively very less adverse effects as compared to hydroquinone.

Factors limiting regeneration of a Near Threatened deciduous tree Pterocarpus marsupium Roxb. in Central India

In the tropical dry deciduous forests of Central India, changes in population structure and regeneration of a Near Threatened tree Pterocarpus marsupium Roxb. (Fabaceae) was monitored over 4 years. Focussing on the effects of biotic disturbance, the study examined seven potential sites, for future restoration measures and management. We examined 46 plots of 0.1 ha size laid in these seven sites from 2017 to 2021. Results compared in all sites revealed that there were hardly any individuals surviving or growing at ‘Sapling’ stage, which is counted as crucial for successful regeneration of a tree species. Among all the study sites, SARA recorded highest average density of seedlings per sample plot followed by BAHO and LAMT. Positive change in ‘Seedlings’ category was recorded only at BAHO (+17.8%) and SARA (+9.1%). Whereas, BIRS recorded highest decline in average density of seedlings (−42.2%) followed by SEMA (−24.3%) and BARH (17.2%). Correlation analysis of biotic pressure on the species, revealed that weed infestation (−0.59) has highest adverse effect on the seedling density followed by Lopping/cutting (−0.33) and livestock & human population (−0.12), indicating an urgent need to undertake assisted natural regeneration (ANR) activities for this species in its natural ranges. Although there were few positive changes in the seedling stage (BAHO +17.8%; SARA +9.1%), but conditions of most sites did not meet the standards necessary for the survival and growth of a tree species. Therefore, the study concludes that lack of ability of seedlings to grow into saplings due to biotic pressure is the main limitation for the natural habitats of P. marsupium in Central India.

Effect of different double‐stranded RNA feeding solutions on the RNA interference of V‐ATPase‐B in Frankliniella occidentalis

AbstractWestern flower thrips (WFT), Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), has posed a serious threat to horticultural and agricultural crop production by feeding, ovipositing, and transmitting plant viruses. RNA interference (RNAi) technology is considered a potential strategy for insect pest control. A main method of RNAi research on WFT is the feeding method for delivering double‐stranded RNA (dsRNA). The feeding solution plays an important role in the stable delivery of dsRNA. In this study, we screened for a feeding solution suitable for RNAi experiments and investigated the effects of five feeding solutions on the survival of WFT adults and nymphs. The effect of mixed V‐ATPase‐B dsRNA in various feeding solutions on the RNAi efficiency of WFT was analysed. The Luria–Bertani‐based and ‘tryptone soy broth and yeast’ (TSBY) solution had a higher adverse effect than the other feeding solutions on the survival of adults and nymphs of WFT, whereas sucrose, pollen, and honey solution could maintain higher survival rates in both nymph and adult thrips. Sucrose solution and TSBY solution mixed with dsRNA had no significant knockdown effects on V‐ATPase‐B transcription level. Honey and pollen solution mixed dsRNA, however, not only significantly decreased V‐ATPase‐B transcription level, but also reduced the survival rate and fertility of female adults to a certain extent. The stability of dsRNA was improved in honey solution. The results of this study provide a feasible reference for the selection of feeding solutions for RNAi experiments for feeding of WTF with dsRNA.

The behavior of heavy metals in relation to their influence on the common bean (Phaseolus vulgaris) symbiosis

Heavy metals (HMs) concentration is continuously increasing in agricultural soils, mainly through anthropogenic activities. Among HMs, cadmium (Cd), lead (Pb), and nickel (Ni) have shown more hazardous effects on living organs by bioaccumulation throughout the food chain. A pot experiment was arranged as a completely randomized factorial design with four replications to investigate the effects of Cd, Pb, and Ni on biological, physiological, and biochemical responses of common bean (Phaseolus vulgaris). The present study results revealed that Cd, Pb, and Ni effects on biological, physiological, and biochemical characteristics of common bean include root and shoot dry weight, shoot to root ratio, pod number, root and shoot nitrogen content, nodule number, nodule dry weight, photosynthesis pigments, leaf greenness (SPAD), DPPH scavenging, the activity of guaiacol peroxidase (POD), superoxide dismutase (SOD), ascorbate (APX), and Catalase (CAT). HMs toxicity caused a significant decrease in root and shoot dry weight, shoot to root ratio, pod number, root and shoot nitrogen content, nodule number, nodule dry weight, and intensively decreased by increasing HMs concentration in soil. HMs toxicity also decreased photosynthesis pigments and leaf greenness (SPAD). Moreover, biochemical characteristics include DPPH scavenging, POD, SOD, APX, and CAT activities improved by increasing HMs concentration. The findings also revealed that the highest adverse effects on common bean's biological, physiological, and biochemical characteristics were observed at Cd treatments compared to Pb and Ni. BCF, BAC, TF, and TE% for Cd and Ni showed a negative relationship with their concentration in soil. However, TF and TE% were improved by increasing Pb concentration in soil. Therefore, a common bean restricts the absorption and translocation of Cd, Pb, and Ni in highly polluted soil to avoid the toxic effects of Cd and Ni.

The link between public debt and investment: an empirical assessment from emerging markets

ABSTRACT This paper provides empirical evidence of the relationship between public debt/GDP ratio and investment. Based on panel data analysis considering 24 emerging markets from 1996 to 2018, we investigate the effect of an increase in public debt on investment at three levels: aggregate, private sector, and public sector. Moreover, we consider the possibility of the global financial crisis of 2007–2008 (GFC) has changed the relationship between public debt and investment. We also assess the effect of a public debt/GDP ratio higher than the prudential level of 60% on investment. The findings indicate that an increase in the public debt/GDP ratio has a significant harmful effect on investment. In particular, we observe that after the GFC, the adverse effect of a higher public debt/GDP ratio on investment increased considerably. Moreover, our results show that the highest adverse effect of a rise in the public debt/GDP ratio is on the public sector investment.

Safety, immunogenicity, and transplacental antibody transport of conjugated and polysaccharide pneumococcal vaccines administered to pregnant women with HIV: a multicentre randomised controlled trial

Pneumococcus remains an important cause of morbidity in pregnant women with HIV and their infants. We compared the safety and immunogenicity of PCV-10 and PPV-23 with placebo administered in pregnancy. This double-blind, multicentre, randomised controlled trial was done at eight outpatient clinics in Brazil. Eligible participants were adult women with HIV who were pregnant at a gestational age between 14 weeks and less than 34 weeks and who were taking antiretroviral therapy at study entry. Participants were randomly assigned (1:1:1) to receive either PCV-10, PPV-23, or placebo. Participants and study teams were unaware of treatment allocation. Antibodies against seven vaccine serotypes in PCV-10 and PPV-23 were measured by ELISA. The primary outcomes were maternal and infant safety assessed by the frequency of adverse events of grade 3 or higher; maternal seroresponse (defined as ≥2-fold increase in antibodies from baseline to 28 days after immunisation) against five or more serotypes; and infant seroprotection (defined as anti-pneumococcus antibody concentration of ≥0·35 μg/mL) against five or more serotypes at 8 weeks of life. The study was powered to detect differences of 20% or higher in the primary immunological outcomes between treatment groups. This trial is registered with ClinicalTrials.gov, NCT02717494. Between April 1, 2016, and Nov 30, 2017, we enrolled 347 pregnant women with HIV, of whom 116 were randomly assigned to the PCV-10 group, 115 to the PPV-23 group, and 116 to the placebo group. One participant in the PCV-10 group did not receive the vaccine and was excluded from subsequent analyses. The frequency of adverse events of grade 3 or higher during the first 4 weeks was similar in the vaccine and placebo groups (3% [90% CI 1-7] for the PCV-10 group, 2% [0-5] for the PPV-23 group, and 3% [1-8] for the placebo group). However, injection site and systemic grade 2 adverse reactions were reported more frequently during the first 4 weeks in the vaccine groups than in the placebo group (14% [9-20] for the PCV-10 group, 7% [4-12] for the PPV-23 group, and 3% [1-7] for the placebo group). The frequency of grade 3 or higher adverse effects was similar across maternal treatment groups (20% [14-27] for the PCV-10 group, 21% [14-28] for the PPV-23 group, and 20% [14-27] for the placebo group). Seroresponses against five or more serotypes were present in 74 (65%) of 114 women in the PCV-10 group, 72 (65%) of 110 women in the PPV-23 group, and none of the 113 women in the placebo group at 4 weeks post vaccination (p<0·0001 for PPV-23 group vs placebo and PCV-10 group vs placebo). Seroresponse differences of 20% or higher in vaccine compared with placebo recipients persisted up to 24 weeks post partum. At birth, 76 (67%) of 113 infants in the PCV-10 group, 62 (57%) of 109 infants in the PPV-23 group, and 19 (17%) of 115 infants in the placebo group had seroprotection against five or more serotypes (p<0·0001 for PPV-23 vs placebo and PCV-10 vs placebo). At 8 weeks, the outcome was met by 20 (19%) of 108 infants in the PCV-10 group, 24 (23%) of 104 infants in the PPV-23 group, and one (1%) of 109 infants in the placebo group (p<0·0001). Although a difference of 20% or higher compared with placebo was observed only in the infants who received PPV-23 at 8 weeks of life, the difference between the two vaccine groups was not appreciable. PCV-10 and PPV-23 were equally safe and immunogenic in pregnant women with HIV and conferred similar levels of seroprotection to their infants. In areas in which childhood PCV administration decreased the circulation of PCV serotypes, PPV-23 administration to pregnant women with HIV might be more advantageous than PCV by virtue of including a broader range of serotypes. Eunice Kennedy Shriver National Institute of Child Health and Human Development. For the Portuguese translation of the abstract see Supplementary Materials section.

Economic and environmental assessment of tobacco production in Northern Iran

Environmental and economic aspects of a production system are two main pillars to study the sustainability of the system. In this regard, the purpose of this study was the economic and environmental assessment of tobacco (Nicotiana tabacum) production in rainfed and irrigated systems in northern Iran. The data were collected from 133 rainfed and 176 irrigated tobacco farms in three provinces of Mazandaran, Golestan, and Guilan in Iran. The standard method of life cycle assessment (LCA) provided by ISO 14040-44 was used to study the environmental impacts. Four economic indices, including gross income, net income, benefit to cost ratio, and economic productivity, were examined for the economic analysis of the cropping systems. In the study of environmental impacts, the average value ​​of global warming input was 2624.11 kgCO2eq. The comparison of rainfed and irrigated systems revealed that the rainfed system in all impact categories had the highest environmental impact. Moreover, emissions from on-site operations and the use of two inputs of natural gas and chemical fertilizers had the highest effect on characterization indices. The results also showed that tobacco production had the highest adverse effects on resources and a significant amount of fossil fuels used in the production process had the largest share in increasing this damage group. Economic analysis also highlighted that the average net income and benefit to cost ratio were 6646.86 $ ha−1 and 2.27. The irrigated system had higher values of the indices than the rainfed system, indicating the higher profitability of the irrigated production system.

Effects of Parental Attitudes Toward Spousal Violence on Early Childhood Development and Learning Support Among Ghanaian Children.

The prevalence of condoning attitudes toward spousal violence (SV) is high in Ghana, yet much is not known about how the development of children is compromised in households where attitudes toward SV are tolerated. This study is premised on two objectives: (a) examination of the effect of parents condoning attitudes toward SV on early childhood development; and (b) investigation of the effect of parents condoning attitudes toward SV on the amount of learning support children receive from household members. Data on 2,740 children aged between 36 and 59 months were drawn from the 2011 Ghana Multiple Indicator Cluster Survey for the first objective and 1,595 households with children aged between 4 and 15 years were sourced from the 2014 Ghana Demographic and Health Survey for the second. Analytical methods employed are descriptive statistics, instrumental variable (IV), and ordinary least squares (OLS) micro-econometric estimation techniques. The findings suggest that parents who condone attitudes toward SV reduce early childhood development by 3.269 units. Compared with the physical and socioemotional domains, parents tolerating attitudes toward SV have the highest adverse effect on the literacy, numeracy, and learning development domain of early childhood development (2.916 units). In addition, households that accept attitudes toward SV reduce the amount of learning support offered to children by 0.261 units, and every additional attitude toward SV acceptance reduces child learning support by 0.079 units. Attitudes of parents toward condoning SV retard the early development of children, impair children's cognitive development, and compromise the amount of learning support children receive from household members. This study reinforces the evidence that parental attitudes are related to child outcomes in Ghana. The evidence calls for strengthening healthy family environments and child protection systems through behavioral change communication interventions and awareness creation among parents.

A qualitative risk assessment approach to microbial foodborne hazards in Brazilian intensive pork production: A step towards risk prioritization

The application of biosecurity measures in pig farms has prompted a shift in epidemiological reality, altering the risk profile attributed to the consumption of pork. The inspection of pig carcasses in Brazil is based on incisions and palpations to seek lesions mainly related to classic zoonotic diseases. We describe the use of a qualitative risk assessment from the farm to the table to characterize the risk of foodborne disease caused by biological hazards to humans due to the consumption of pork. The model was adapted from the Codex Alimentarius and comprises four steps: (I) hazard identification, (II) hazard characterization, (III) exposure assessment, and (IV) risk characterization. The exposure assessment step considers the release of hazards at a pre-harvest level (i.e., swine in herds) and the amplification or reduction of the release during the procedure to obtain pork from a carcass. Risk characterization is classified into five levels, from very low to very high. No hazard had very high risk, Salmonella sp. [nontyphoidal] had high risk, no hazard had moderate risk, seven hazards had low risk, and other hazards had very low risk. When the initial release was increased, the risk for hazards with higher adverse effects (e.g. C. botulinum, B. suis, and E. coli [STEC]) increased to very high or high. The uncertainty was very high for seven hazards and very low for three. These findings can help the Brazilian Ministry of Agriculture discuss changes in the routine inspection of the carcasses of pigs raised in industrial systems in Brazil.