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Duchenne muscular dystrophy (DMD) results in a progressive loss of functional skeletal muscle mass (MM) and replacement with fibrofatty tissue. Accurate evaluation of MM in DMD patients has not previously been available. Our objective was to measure MM using the D3creatine (D3Cr) dilution method and determine its relationship with strength and functional capacity in patients with DMD over a wide range of ages. Subjects were recruited for participation in a 12 month, longitudinal, observational study. Here, we report the baseline data. A 20 mg dose of D3Cr dissolved in water was ingested by 92 patients with DMD (ages 4-25 years) followed later with a fasting urine sample. Enrichment of D3creatinine was determined by liquid chromatography-mass spectrometry analysis. The North Star Ambulatory Assessment (NSAA) total score was determined for ambulatory participants, and the Performance of Upper Limb (PUL 2.0) total score and grip strength for all participants. We observed a significant age-associated increase in body weight along with a substantial decrease in MM/body weight (%MM). MM and %MM were associated with PUL score (r = 0.517, P

Adsorption is regarded as an efficient method to eliminate per- and polyfluoroalkyl substances from an aqueous solution. In the present investigation, an adsorbent based on rice husks (RHs) was successfully prepared by phosphoric acid (PA) activation and dielectric barrier discharge (DBD) plasma treatment, and it was used to adsorb perfluorooctanoic acid (PFOA) from water. The electrodes employed in the experiment were planar type. This research investigated RH surface properties and adsorption capacity before and after modification using DBD plasma. The results revealed that the He-O2 plasma modification introduced oxygen-containing functional groups and increased the PFOA removal efficiency. Increasing the oxygen content and total gas flow rate to 30 vol.% and 1.5 L/min, respectively, with 10 min of RH plasma treatment time at 100 W plasma discharge power enhanced the PFOA removal efficiency to 92.0%, while non-treated RH showed the removal efficiency of only 46.4%. The removal efficiency of the solution increased to 96.7% upon adjusting the pH to 4. The adsorption equilibrium isotherms fitted the Langmuir model, and the adsorption kinetic followed the pseudo-second-order model. The maximum adsorption capacity was 565 mg/g when the Langmuir isotherm model was applied.

ABSTRACTBackground: Imagery rescripting (ImRs) has shown to be an effective treatment for posttraumatic stress disorders (PTSD) resulting from childhood-related trauma. The current theory is that the change of meaning of the trauma memory is central to the treatment. Several authors have suggested that the expression of needs, feelings and actions may act as potential healing factors, but little specific research aimed at (in)validating this hypothesis has been done so far.Objective: In this study we investigated to what extent the expression of inhibited action tendencies and the fulfilling of needs lead to the reduction of PTSD symptoms in clients with early childhood trauma.Method: Recordings of 249 therapy sessions of 24 ImRs treatments were rated with an observation instrument developed for this purpose, after which the scores were related to pre and posttreatment symptoms, assessed with the Impact of Events Scale-Revised (IES-R).Results: Scores on the IES-R decreased from pretreatment to posttreatment. The two subscales of the NATS (At-scale and N-scale)significantly predicted the posttreatment scores on the IES-R after controlling for the influence of pretreatment IES-R scores: the better the expression of inhibited action tendencies and the better the fulfilling of needs, the lower the symptoms after treatment.Conclusions: This pilot study on the underlying mechanisms of ImRs in PTSD treatment has shown that the expression of action tendencies and fulfilling basic needs during ImRs are associated with a decrease in PTSD symptoms after treatment, and that actions and basic needs cannot be viewed separately. Follow-up research could focus on which of the six domains of the Needs and Action tendencies Scale (NATS) has the greatest effect on the reduction of PTSD symptoms. With this information we can further improve the ImRs protocol.

ABSTRACT Plasmodium parasites, the causative organism of malaria, caused over 600,000 deaths in 2022. In Mali, Plasmodium falciparum causes the majority of malaria cases and deaths and is transmitted seasonally. Anti-malarial immunity develops slowly over repeated exposures to P. falciparum and some aspects of this immunity (e.g., antibody titers) wane during the non-transmission, dry season. Here, we sequenced RNA from 33 pediatric blood samples collected during P. falciparum infections at the beginning or end of a transmission season, and characterized the host and parasite gene expression profiles for paired, consecutive infections. We found that human gene expression changes more over the course of one transmission season than between seasons, with signatures of partial development of an adaptive immune response during one transmission season and stability in gene expression during the dry season. Additionally, we found that P. falciparum gene expression did not vary with timing during the season and remained stable both across and between seasons, despite varying human immune pressures. Our results provide insights into the dynamics of anti-malarial immune response development over short time frames that could be exploited by future vaccine and prevention efforts.IMPORTANCEOur work seeks to understand how the immune response to Plasmodium falciparum malaria changes between infections that occur during low and high malaria transmission seasons, and highlights that immune gene expression changes more during the high transmission season. This provides important insight into the dynamics of the anti-malarial immune response that are important to characterize over these short time frames to better understand how to exploit this immune response with future vaccine efforts.

Introduction Five of the neglected tropical diseases use a strategy of preventative chemotherapy distributed via mass drug administration (MDA) for all eligible people living in endemic areas. To be successful, high coverage must be sustained over multiple rounds. Therefore, it will be difficult to reach elimination as a public health problem using MDA if there remain clusters of people who have never been treated. The study aims to explore the reasons why people with high mobility report being never treated during MDA and to provide evidence to support the development of standardised questions for data collection using qualitative research tools.Methods We conducted an exploratory study using qualitative methods among displaced people, nomads/transhumants and economic migrants who self-reported that they had never been treated during MDA in the health districts of Tominian and Kalabancoro in Mali. Data were collected through in-depth individual interviews and focus group discussions. Nvivo V.14 software was used for data management and analysis.Results The main reasons reported for never treatment included: geographical mobility, lack of awareness/information, negative rumours, fear of side effects, conflict and insecurity and logistical difficulties faced in reaching these populations. Proposed solutions included involving communities in the MDA, increasing awareness and information campaigns, effectively managing side effects, and designing and implementing flexible and effective interventions.Conclusion This study highlights that there are people with high mobility who may never have been treated during any round of MDA. The reasons for never treatment highlight the challenges faced when reaching particular groups during MDA activities/interventions. Suggested remedies will require programmes to implement more flexible and tailored interventions. Customised approaches based on the context are essential to guarantee fair access to preventive chemotherapy. Effective interventions must consider the supply and demand side in crafting interventions. This research adds to the evidence base to understand never treatment, particularly among highly mobile population groups and in schistosomiasis elimination programmes.

Background: Small rodents and insectivores are potential reservoirs of many pathogens transmissible to humans, such as bacteria, parasites and viruses responsible for epidemics in sub-Saharan Africa, particularly in West Africa. Few studies on small mammal species in West Africa are available. Our previous findings from a study investigating emerging pathogens in two localities in Mali has determined the prevalence of pathogens in small mammals (rodents and insectivores). We used the data collected from this small mammal population with different eco-climatic characteristics to test hypothesis that small mammal distribution in different eco-climatic settings could explain the diversity and frequency of pathogens they carry. Methods: Sessions of trapping were carried out in December 2016 in Faladjè and Bougouni with “Besançon tous services” (BTS) wire mesh traps baited with peanut butter and/or onion. All animals captured were identified morphologically. Results: Out of 123 small rodents and insectivores captured over 674 trap-nights, 75 (60.97%) were from Faladjè and 48 (39.02%) from Bougouni. Of these, six species of small rodents belonged to the family Muridae (Mastomys erythroleucus, Mastomys natalensis, Rattus rattus, Praomys daltoni, Gerbilliscus gambianus, Taterillus gracilis) and two species of insectivores associated with the genus Crocidura spp. belonged to the family Soricidae and Erinaceidae (Crocidura cf olivieri and Atelerix cf albiventris), respectively. There is low species diversity within these two areas, but the variation in relative abundance is significant (binomial test, p ˂ 0.05) between Faladjè and Bougouni. Mastomys erythroleucus was the most dominant species (57.33%, 43/75) in Faladjè, while R. rattus dominated (37.5%,18/48) in Bougouni. Conclusions: These two species of small mammals potentially involved in the transmission of bacteria, parasites and pathogenic viruses to humans are differently present in two distinct eco-climatic areas in Mali.

The dental prosthesis is defined as an artificial device intended to replace the missing tooth or teeth and the related tissues. Clinical reality places us in front of an infinite dental edentation situation. For the rehabilitation of missing teeth, it is often necessary to manage simultaneously the use of all prosthetic techniques: partial and total prosthesis, fixed prosthesis and implantology.The aim of this investigation is to evaluate dental prosthesis needs in the University Hospital of Odonto-Stomatology of Bamako (CHUOS).A survey was conducted at Bamako University Hospital over a period of one month. The study included 400 patients who consulted for making dental prosthesis. Patients with 1-4 teeth to replace in the maxillar represented 30, 1% of cases and 30,7% in the mandible. The results showed the highest rate concerning partial removable denture prosthesis preference (83%) in comparison with fixed prosthesis which represented only 8, 75% of cases. Also, the partial removable prosthesis was diagnosed in 52,25% of cases. Edentation can be the cause of several problems in the oral cavity, hence the need to sensitize the population of the importance of oral health and the importance of wearing the prosthesis in case of losing teeth.

Hypothyroidism is associated with a decreased health-related quality of life (HRQoL). We hypothesized that individuals with hypothyroidism (defined as us e of thyroid hormone (TH)) and especially those having an impaired HRQoL are characterized by a high prevalence of comorbid disorders and that the impact of hypothyroidism and comorbidity on HRQoL is synergistic. Presence of comorbidity was based on data obtained using structured questionnaires, physical examination, biochemical measurements and verified medication use. Single morbidities were clustered into 14 different disease domains. HRQoL was measured using the RAND-36. Logistic regression analyses were used to determine the effect of TH use on the odds of having an affected disease domain and a lower score than an age- and sex-specific reference value for HRQoL. TH was used by 4537/14,7201 participants of the population-based Lifelines cohort with a mean (± s.d.) age of 51.0 ± 12.8 years (88% females). Eighty-five percent of the TH users had ≥1 affected disease domain in contrast to 71% of nonusers. TH use was associated with a higher odds of 13 out of 14 affected disease domains independent of age and sex. In a multivariable model, TH use was associated with a decreased HRQoL across six out of eight dimensions. No significant interactions between TH use and affected disease d omains were observed. TH users with an impaired HRQoL had significantly more comorbidity than those not having an impaired HRQoL. In this large, population-based study, we demonstrated that TH users had more comorbidity than individuals not using TH. The coexistence of other chronic medical conditions in subjects with TH use led to further lowering of HRQoL in an additive manner.

BackgroundNintedanib is a triple-angiokinase inhibitor with potential activity in patients with advanced thyroid cancers, as radioiodine refractory differentiated thyroid cancer (RAIR DTC) and medullary thyroid cancer (MTC).DesignEORTC-1209 (NCT01788982) was a double-blind randomized (2:1 ratio) placebo-controlled phase II, multi-cohort study exploring the efficacy and safety of nintedanib in patients with progressive, locally advanced, and/or metastatic RAIR DTC and MTC. The primary endpoint was progression-free survival (PFS) in the per-protocol (PP) population for both cohorts. Secondary endpoints included response rate, duration of response, overall survival (OS), and safety.ResultsRAIR DTC cohort: Seventy out of the 75 planned patients with RAIR DTC (median age, 66 years; 39 women) who had progressed after one (76%) or two lines (24%) of previous systemic therapy were randomized to receive either nintedanib (N = 45) or placebo (N = 25). Of these, 69 patients started treatment and 56 met all inclusion criteria (PP). At data cutoff, the median duration of follow-up was 26.3 months in the nintedanib arm and 19.8 months in the placebo arm. In the PP population, the median PFS was 3.7 months [80% confidence interval (CI), 1.9–6.5] in the nintedanib arm and 2.9 months (80% CI, 2.0–5.6) in the placebo arm (HR = 0.65; 80% CI, 0.42–0.99; one-sided log-rank test P = 0.0947). No objective response was observed. The median OS was 29.6 months [80% CI, 15.2–not reached (NR)] in the nintedanib arm and not reached in the placebo arm. Grade 3–4 adverse events of any attribution occurred in 50% of patients receiving nintedanib and in 36% of patients receiving placebo. MTC cohort: Thirty-one out of the 67 planned patients with MTC (median age, 57 years; eight women) who had progressed after one (68%) or two (32%) lines of previous systemic therapy were randomized to receive either nintedanib (N = 22) or placebo (N = 9). Of these, 20 patients (15 in the nintedanib arm and five in the placebo arm) started treatment and met all inclusion criteria (PP). The median PFS was 7.0 months (80% CI, 1.9–8.7) in the nintedanib arm and 3.9 months (80% CI, 3.0–5.5) in the placebo arm (HR = 0.49; 95% CI, 0.16–1.53). No objective response was reported. The median OS was 16.4 months (80% CI, 12.1–24.9) in the nintedanib arm and 12.3 months (80% CI, 7.1–NR) in the placebo arm. Grade 3–4 adverse events of any attribution during the blinded period occurred in 59.1% of patients receiving nintedanib and in 33.3% of patients receiving placebo.ConclusionThis study did not suggest a clinically significant improvement of PFS with nintedanib over placebo in patients with pretreated RAIR DTC and MTC.

Abstract Adsorption is regarded as an efficient method to eliminate per- and polyfluoroalkyl substances from an aqueous solution. In the present investigation, an adsorbent based on rice husks (RHs) was successfully prepared by phosphoric acid (PA) activation and dielectric barrier discharge (DBD) plasma treatment, and it was used to adsorb perfluorooctanoic acid (PFOA) from water. The electrodes employed in the experiment were planar type. This research investigated RH surface properties and adsorption capacity before and after modification using DBD plasma. The results revealed that the He–O2 plasma modification introduced oxygen-containing functional groups and increased the PFOA removal efficiency. Increasing the oxygen content and total gas flow rate to 30 vol.% and 1.5 L/min, respectively, with 10 min of RH plasma treatment time at 100 W plasma discharge power enhanced the PFOA removal efficiency to 92.0%, while non-treated RH showed the removal efficiency of only 46.4%. The removal efficiency of the solution increased to 96.7% upon adjusting the pH to 4. The adsorption equilibrium isotherms fitted the Langmuir model, and the adsorption kinetic followed the pseudo-second-order model. The maximum adsorption capacity was 565 mg/g when the Langmuir isotherm model was applied.

Although Bantu languages are not known for having grammaticalized and obligatory systems of evidentiality, research is uncovering more and more evidential contrasts and evidential strategies, as well as expressions of related categories like mirativity. In this article, I describe, with examples from the literature and my own research, two domains in which I believe targeted investigations are likely to uncover additional examples of evidential and mirative meanings. The first domain is quotatives, which very frequently have evidential and mirative functions, but which are largely underdescribed across Bantu. The second domain is tense and aspect, which is somewhat better described, but where little is known about associated evidential functions. I especially highlight cases in which two forms have overlapping denotative temporal or aspectual meanings, and evidential and similar contrasts can arise as a result.

Abstract This article explores the fundamental right to food, examining its legal framework, its relationship with other human rights, and the efforts being made globally to improve this right. It begins by looking at international and national laws that protect the right to food and examining their importance in ensuring food security and sovereignty. It then explores how food rights intersect with other rights, such as health, education, and labor, revealing the interrelated web of human rights. The article further highlights how the right to food is closely tied to the objectives of reducing poverty and promoting social justice, which are crucial components in the collective effort to achieve food security for all. Additionally, it evaluates the effectiveness of current policies and strategies in promoting the right to food, particularly in sub‐Saharan Africa. The novelty of the article is that it brings into perspective, the encumbrance of food sovereignty in sub‐Saharan Africa and concludes with potential solutions.

RasGRP1 is a Ras guanine nucleotide exchange factor, and an essential regulator of lymphocyte receptor signaling. In mice, Rasgrp1 deletion results in defective T lymphocyte development. RASGRP1-deficient patients suffer from immune deficiency, and the RASGRP1 gene has been linked to autoimmunity. However, how RasGRP1 levels are regulated, and if RasGRP1 dosage alterations contribute to autoimmunity remains unknown. We demonstrate that diminished Rasgrp1 expression caused defective T lymphocyte selection in C57BL/6 mice, and that the severity of inflammatory disease inversely correlates with Rasgrp1 expression levels. In patients with autoimmunity, active inflammation correlated with decreased RASGRP1 levels in CD4+ T cells. By analyzing H3K27 acetylation profiles in human T cells, we identified a RASGRP1 enhancer that harbors autoimmunity-associated SNPs. CRISPR-Cas9 disruption of this enhancer caused lower RasGRP1 expression, and decreased binding of RUNX1 and CBFB transcription factors. Analyzing patients with autoimmunity, we detected reduced RUNX1 expression in CD4+ T cells. Lastly, we mechanistically link RUNX1 to transcriptional regulation of RASGRP1 to reveal a key circuit regulating RasGRP1 expression, which is vital to prevent inflammatory disease.

Knowledge of the Plasmodium falciparum antigens that comprise the human liver stage immunoproteome is important for pre-erythrocytic vaccine development, but, compared with the erythrocytic stage immunoproteome, more challenging to classify. Previous studies of P. falciparum antibody responses report IgG and rarely IgA responses. We assessed IgG and IgA antibody responses in adult sera collected during two controlled human malaria infection (CHMI) studies in malaria-naïve volunteers and in 1- to 6-year-old malaria-exposed Malian children on a 251 P. falciparum antigen protein microarray. IgG profiles in the two CHMI groups were equivalent and differed from Malian children. IgA profiles were robust in the CHMI groups and a subset of Malian children. We describe immunoproteome differences in naïve vs. exposed individuals and report pre-erythrocytic proteins recognized by the immune system. IgA responses detected in this study expand the list of pre-erythrocytic antigens for further characterization as potential vaccine candidates.

Background: The role of postoperative external beam radiotherapy (EBRT) in patients with residual iodine refractory-differentiated thyroid cancer (IR-DTC) is still inconclusive. The aim of this retrospective study was to evaluate locoregional control (LRC) and overall survival (OS), and potential side effects after postoperative EB RT for both microscopic and macroscopic non-radically resected, locally advanced IR-DTC. Methods: Between 1990 and 2016, 49 patients with locally advanced IR-D TC received EBRT for microscopic (R1; n = 28) or macroscopic (R2; n = 21) locoregional residual disease. For more insight into the added effect of EBRT, we perf ormed an intrapatient sub-analysis in 32 patients who had undergone more than 1 surgical intervention, comparing LRC after primary, curative-intended surgery with LRC after repeated surgery plus EBRT. To estimate LRC and OS, we used Kaplan–Meier curves. From 2007 onward, we prospectively recorded toxicity data in our head and neck cancer database (n = 10). Results: LRC rates 5 years after EBRT were higher for R1 (84.3%) than for R2 (44.9%) residual disease (P = 0.016). The 5-year OS rate after EBRT was 72.1% for R1 and 33. 1% for R2 disease (P = 0.003). In the intrapatient analysis (n = 32), LRC rates were 6.3% 5 years after only initial surgery and 77.9% after repeated sur gery with EBRT (P < 0.001). Acute toxicity was limited to grade I and II xerostomia, mucosi tis, and hoarseness; only one patient developed late grade III dysphagia. Conclusions: Postoperative EBRT is associated with long-lasting LRC and OS with acceptable toxicity in patients with locally advanced IR-DTC, e specially in microscopic residual disease.

Objective: Thyroglobulin (Tg) is an established tumor marker for different iated thyroid carcinoma (DTC) patients. However, Tg immunoassays can be subject to Tg autoantibody (TgAb) interference resulting in incorrect Tg values. Therefore, Tg measurement with liquid chromatography-tandem mass spectrometry (LC-MS/MS) could be promising in patients with TgAbs. In this study, we compared Tg IRMA and Tg-LC-MS/MS analytically in the presence of TgAbs. Furthermore, we compared the clinical interpretation of results obtained by both Tg assays in DTC patients with lower TgAbs titers (>100)). In patients(n = 91) with lower TgAb titers at the time of 131I ablation therapy, the Tg assays showed a clinical concordance of 91.2, 87.9, and 98.9%, respectively, using a Tg cut-off value of 1.0, 2.0, and 5.0 ng/m L. Conclusions: In DTC patients with lower titer TgAbs, Tg-IRMA is still a reliable and useful tumor marker. In DTC patients with potentially interfering TgAbs, Tg-IRMA values decreased due to TgAb interference.