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Plasmodium falciparum infection can lead to a life threatening disease and the pathogenetic mechanisms of severe manifestations are not fully understood. Here, we investigated the capacity of P. falciparum -parasitized red blood cells (PRBC) from 45 children with clinical malaria to induce endothelial cell (EC) apoptosis. In all subjects, PRBC that cytoadhered to ECs could be found albeit to a variable degree. By contrast, PRBC that induce EC apoptosis were found only in nine (20%) subjects. Interestingly, children with neurological manifestations were significantly more likely to harbour apoptogenic strains. There was no quantitative relationship between the capacity of these isolates to cytoadhere and apoptosis induction. We hypothesize that P. falciparum -encoded molecules could be responsible for apoptosis induction and therefore suggest new insights in the pathogenesis of P. falciparum malaria. Further investigations are currently in progress to determine whether these results can be confirmed and to identify putative parasite apoptogenic factors. [ABSTRACT FROM AUTHOR]

A simplified, combined protocol admitting children with a mid‐upper‐arm circumference (MUAC) of <125 mm or oedema to malnutrition treatment with ready‐to‐use therapeutic food (RUTF) uses two sachets of RUTF per day of those with MUAC < 115 mm and/or oedema and one sachet of RUTF per day for those with MUAC 115–<125 mm. This treatment previously demonstrated noninferior programmatic outcomes compared with standard treatment and high recovery in a routine setting. We aimed to observe the protocol's effectiveness in a routine setting at scale, in two health districts of the Central African Republic through an observational cohort study. The pilot enrolled children for 1 year in consortium by the Ministry of Health and nongovernmental partners. A total of 7909 children were admitted to the simplified, combined treatment. Treatment resulted in an 81.2% overall recovery, with a mean length of stay (LOS) of 38.7 days and a mean RUTF consumption of 43.4 sachets per child treated. Among children admitted with MUAC < 115 mm or oedema, 67.9% recovered with a mean LOS of 48.1 days and consumed an average of 70.9 RUTF sachets. Programme performance differed between the two districts, with an overall defaulting rate of 31.1% in the Kouango‐Grimari health district, compared to 8.2% in Kemo. Response to treatment by children admitted with severe acute malnutrition (SAM) by MUAC and SAM by oedema was similar. The simplified, combined protocol resulted in a satisfactory overall recovery and low RUTF consumption per child treated, with further need to understand defaulting in the context. Key messages: The simplified, combined protocol with a mid‐upper‐arm circumference (MUAC)‐based ready‐to‐use therapeutic food (RUTF) resulted in a recovery rate that reached SPHERE standards, low length of stay and low RUTF consumption per child among all children treated.Response to treatment was similar among children admitted with severe acute malnutrition (SAM) by oedema and those admitted SAM by MUAC.Contextual factors such as insecurity and stockouts in treatment products affect programme outcomes by increasing defaulting and decreasing recovery rates.The simplified, combined protocol might present an opportunity to treat more children with less product; decentralised delivery should continue to be explored. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cell activity is impaired in Chlamydia trachomatis-infected patients. The mechanisms behind the altered NK functions are not clear, but data concerning NK and antibody-dependent cellular cytotoxicity (ADCC) activity have been reported. To investigate whether this impairment is related to a defect at the target cell binding and/or the postbinding level, we evaluated highly purified NK cells obtained from 125 C. trachomatis-infected patients and compared them with 101 normal controls for their ability to kill K-562 and U-937 cell lines using a 51Cr release assay; release tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma); and kill anti-IgM preincubated P-815 cell line (ADCC activity). We found a decrease in the lytic capability of NK cells from C. trachomatis-infected patients against target cell lines; decreased ability to kill bound target cells; and low levels of released TNF-alpha and INF-gamma after incubation with U-937 cells. Taken together, these findings suggest that the impaired NK cell reaction during chlamydial infection is related to defects both at the target and postbinding levels. However, the precise mechanisms remain to be determined. The inability to restore normal NK activity after long-term culture in the presence of high levels of recombinant IL-2 support the hypothesis of an anergic process during chlamydial infection. [ABSTRACT FROM AUTHOR]

Human filariasis due to Loa loa differs from other filariasis in that the majority of infected subjects are without circulating microfilariae (occult loiasis). In search for alternative diagnostic methods, which do not depend on circulating microfilariae or the (rather infrequent) eye-passage of adult worms, it was shown earlier that IgG4 antibodies directed against Loa loa adult worm antigen are apparently a good marker of occult loiasis and specific with regard to the sympatrically occurring Mansonella perstans. In this study we evaluated an IgG4 antibody-based ELISA using crude extract of Loa loa microfilariae (which is easier to obtain than adult worm) to estimate the prevalence of loiasis in 3 villages in South-East Gabon. Of 222 examined individuals (80 children < 16 years, 142 adults) 44 (20%) carried Loa loa microfilariae and 170 (77%) M. perstans. Using the mean OD-value + 1 standard deviation of 9 sera from patients solely infected with M. perstans (from the Gambia, where Loa loa is not endemic) as a cut-off, 35 of the 44 microfilaraemic Loa loa patients and 2 of the 9 Gambian controls were positive. This shows that our method had a sensitivity of 80% and a specificity of 78%. Among the remaining 178 subjects who had no microfilariae of Loa loa, as many as 97 (55%) had significant levels of specific IgG4 antibodies against Loa loa, suggesting that they carried occult loiasis. The mean IgG4 level in these putatively occult loiasis patients was slightly but significantly lower than in microfilaraemic subjects (P < 0.03). In conclusion, despite the limited sensitivity and specificity of our method, IgG4- ELISA at present is a very useful tool in estimating the real prevalence of loiasis in epidemiological surveys and at the individual level can confirm the diagnosis of L. loa amicrofilaraemic subjects with clinical signs suggesting loiasis. [ABSTRACT FROM AUTHOR]

We have designed primers to the conserved region of the erythrocyte binding antigen (EBA)-175 gene which amplify specifically the two alleles by polymerase chain reaction (PCR) and by nested PCR. This approach provides a specific, sensitive and rapid method for genotype determination in a large number of Plasmodium falciparum field isolates. [ABSTRACT FROM AUTHOR]

Aim: Parvalbumin (PV) is a primary calcium buffer in mouse fast skeletal muscle fibers. Previous work showed that PV ablation has a limited impact on cytosolic Ca 2+ ([Ca 2+ ] cyto ) transients and contractile response, while it enhances mitochondrial density and mitochondrial matrix-free calcium concentration ([Ca 2+ ] mito ). Here, we aimed to quantitatively test the hypothesis that mitochondria act to compensate for PV deficiency., Methods: We determined the free Ca 2+ redistribution during a 2 s 60 Hz tetanic stimulation in the sarcoplasmic reticulum, cytosol, and mitochondria. Via a reaction-diffusion Ca 2+ model, we quantitatively evaluated mitochondrial uptake and storage capacity requirements to compensate for PV lack and analyzed possible extracellular export., Results: [Ca 2+ ] mito during tetanic stimulation is greater in knock-out (KO) (1362 ± 392 nM) than in wild-type (WT) (855 ± 392 nM), p < 0.05. Under the assumption of a non-linear intramitochondrial buffering, the model predicts an accumulation of 725 μmoles/L fiber (buffering ratio 1:11 000) in KO, much higher than in WT (137 μmoles/L fiber , ratio 1:4500). The required transport rate via mitochondrial calcium uniporter (MCU) reaches 3 mM/s, compatible with available literature. TEM images of calcium entry units and Mn 2+ quenching showed a greater capacity of store-operated calcium entry in KO compared to WT. However, levels of [Ca 2+ ] cyto during tetanic stimulation were not modulated to variations of extracellular calcium., Conclusions: The model-based analysis of experimentally determined calcium distribution during tetanic stimulation showed that mitochondria can act as a buffer to compensate for the lack of PV. This result contributes to a better understanding of mitochondria's role in modulating [Ca 2+ ] cyto in skeletal muscle fibers., (© 2024 The Author(s). Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

Vascular calcification (VC) is a common complication of chronic kidney disease (CKD) and contributes to an increased risk of cardiovascular morbidity and mortality. However, effective therapies are still unavailable at present. It has been well established that VC associated with CKD is not a passive process of calcium phosphate deposition, but an actively regulated and cell‐mediated process that shares many similarities with bone formation. Additionally, numerous studies have suggested that CKD patients have specific risk factors and contributors to the development of VC, such as hyperphosphatemia, uremic toxins, oxidative stress and inflammation. Although research efforts in the past decade have greatly improved our knowledge of the multiple factors and mechanisms involved in CKD‐related VC, many questions remain unanswered. Moreover, studies from the past decade have demonstrated that epigenetic modifications abnormalities, such as DNA methylation, histone modifications and noncoding RNAs, play an important role in the regulation of VC. This review seeks to provide an overview of the pathophysiological and molecular mechanisms of VC associated with CKD, mainly focusing on the involvement of epigenetic modifications in the initiation and progression of uremic VC, with the aim to develop promising therapies for CKD‐related cardiovascular events in the future. [ABSTRACT FROM AUTHOR]

Our physical and psychological well-being is significantly influenced by how we perceive our body, in addition to our thoughts and emotions associated with it. Dysfunctional body perceptions and attitudes play a key role in the development and maintenance of severe conditions such as eating disorders in both males and females. Given its relevance, some attempts have been made to improve body image assessment methods in terms of perceptual accuracy and body satisfaction taking advantage of technological advances such as virtual reality. However, existing applications have mainly focused on women and clinical conditions. In this study, we presented the Body Image Virtual Reality Assessment (BIVRA), a virtual reality figure rating scale to assess body image in both male and female subjects. We tested BIVRA's ability to measure perceptual accuracy and compared its results with a standardized body satisfaction questionnaire. Additionally, we investigated gender differences. BIVRA was found to be effective in assessing body image. We observed that a perceptually based task successfully captured both low and high levels of body representations, shedding light on the significant gender differences. The association between BIVRA and the body satisfaction questionnaires was moderated by gender, with a stronger association for women. While further validation of BIVRA is needed to fully exploit its potential, our results suggest that the integration of virtual reality into the assessment of body image and related disorders may significantly enhance our understanding of individuals struggling with body image issues and has the potential to advance current methods and techniques., (© 2024 The British Psychological Society.)

Background: We aimed to analyze the humoral and cellular response to standard and booster (additional doses) COVID‐19 vaccination in solid organ transplantation (SOT) and the risk factors involved for an impaired response. Methods: We did a systematic review and meta‐analysis of studies published up until January 11, 2022, that reported immunogenicity of COVID‐19 vaccine among SOT. The study is registered with PROSPERO, number CRD42022300547. Results: Of the 1527 studies, 112 studies, which involved 15391 SOT and 2844 healthy controls, were included. SOT showed a low humoral response (effect size [ES]: 0.44 [0.40–0.48]) in overall and in control studies (log‐Odds‐ratio [OR]: −4.46 [−8.10 to −2.35]). The humoral response was highest in liver (ES: 0.67 [0.61–0.74]) followed by heart (ES: 0.45 [0.32–0.59]), kidney (ES: 0.40 [0.36–0.45]), kidney‐pancreas (ES: 0.33 [0.13–0.53]), and lung (0.27 [0.17–0.37]). The meta‐analysis for standard and booster dose (ES: 0.43 [0.39–0.47] vs. 0.51 [0.43–0.54]) showed a marginal increase of 18% efficacy. SOT with prior infection had higher response (ES: 0.94 [0.92–0.96] vs. ES: 0.40 [0.39–0.41]; p‐value <.01). The seroresponse with mRNA‐12723 mRNA was highest 0.52 (0.40–0.64). Mycophenolic acid (OR: 1.42 [1.21–1.63]) and Belatacept (OR: 1.89 [1.3–2.49]) had highest risk for nonresponse. SOT had a parallelly decreased cellular response (ES: 0.42 [0.32–0.52]) in overall and control studies (OR: −3.12 [−0.4.12 to −2.13]). Interpretation: Overall, SOT develops a suboptimal response compared to the general population. Immunosuppression including mycophenolic acid, belatacept, and tacrolimus is associated with decreased response. Booster doses increase the immune response, but further upgradation in vaccination strategy for SOT is required. [ABSTRACT FROM AUTHOR]

Eosinophilic peritonitis (EP) constitutes a significant number of culture‐negative peritonitis cases that can affect 16–60% of the patients who are treated with maintenance peritoneal dialysis (PD). Although it is mainly considered to be the hypersensitivity response of the peritoneum to foreign substances, it can also develop following culture‐positive peritonitis attacks. Besides the presence of more than 100 white blood cells (WBC)/ml, the diagnosis is made with the high number of eosinophils in the dialysate fluid (>10%), usually accompanied by peripheral eosinophilia. In this study, a 12‐year‐old male patient, who was diagnosed as EP as early as in the first week of PD catheter placement and treated with systemic antihistamines was reported. Additionally, clinical aspects and treatment modalities of EP are presented with a detailed literature review. Although EP is usually a self‐limiting clinical manifestation with a benign outcome, it can be overlooked due to the lack of a routine reporting of the count and percentage of peritoneal eosinophils in most centers. For this reason, a detailed examination in culture‐negative peritonitis cases for EP in order to avoid unnecessary antibiotic use for these patients should be the strategy. [ABSTRACT FROM AUTHOR]

On the one hand, the authors maintain that "a pillar of DuBoisian methodology is the taking of a subaltern standpoint....DuBois's sociology...privileged the subaltern standpoint in theorizing racialized modernity" (203). DuBois struggled all his life to dismantle the first but also to define and build the second....The question of group constitution and construction was one of DuBois's central concerns. To which DuBois replies, "the black man is a person who I must i ride "Jim Crow" in Georgia" (DuBois 2007:77, emphasis mine). : Racialized Modernity and the Global Color Line. [Extracted from the article]

In peritoneal dialysis (PD), a cloudy dialysate is an alarming finding. Bacterial peritonitis is the most common cause, however, atypical infections and non-infectious causes must be considered. A 46-year-old man presented with asthenia, paraesthesia, foamy urine and hypertension. Laboratory testing revealed severe azotaemia, anaemia, hyperkalaemia and nephrotic-range proteinuria. Haemodialysis was started through a central venous catheter. Later, due to patient preference, a Tenckhoff catheter was inserted. Conversion to PD occurred 3 weeks later, during hospitalization for a presumed central line infection. A month later, the patient was hospitalized for neutropenic fever. He was diagnosed an acute parvovirus infection and was discharged under isoniazid for latent tuberculosis. Four months later, the patient presented with fever and a cloudy effluent. Peritoneal fluid (PF) cytology was suggestive of infectious peritonitis, but the symptoms persisted despite antibiotic therapy. Bacterial and mycological cultures were negative. No neoplastic cells were detected. Mycobacterium tuberculosis eventually grew in PF cultures, despite previous negative molecular tests. Directed therapy was then initiated with excellent response. Thus, facing a cloudy effluent, one must consider multiple aetiologies. Diagnosis of peritoneal tuberculosis is hampered by the lack of highly sensitive and specific exams. Here, diagnosis was only possible due to positive mycobacterial cultures. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is one of the most common chronic diseases manifesting in early life, with the prevalence increasing worldwide at a rate of approximately 3% per annum. The prolonged hyperglycaemia characteristic of T1D upregulates the receptor for advanced glycation end products (RAGE) and accelerates the formation of RAGE ligands, including advanced glycation end products, high‐mobility group protein B1, S100 calcium‐binding proteins, and amyloid‐beta. Interestingly, changes in the expression of RAGE and these ligands are evident in patients before the onset of T1D. RAGE signals via various proinflammatory cascades, resulting in the production of reactive oxygen species and cytokines. A large number of proinflammatory ligands that can signal via RAGE have been implicated in several chronic diseases, including T1D. Therefore, it is unsurprising that RAGE has become a potential therapeutic target for the treatment and prevention of disease. In this review, we will explore how RAGE might be targeted to prevent the development of T1D. [ABSTRACT FROM AUTHOR]

Diets of West African (WA) smallholder farmers are built on pearl millet [Pennisetum glaucum (L.) R. Br.]. Sustainable pearl millet hybrid breeding is challenging in WA, mostly due to an extensive genetic diversity combined with a high degree of admixture. In the absence of natural heterotic groups, understanding combining ability patterns can enable systematic development of heterotic groups and make sustainable hybrid breeding feasible. The objectives of this study were to evaluate heterosis and combining ability patterns and their relationship with genetic distance among WA pearl millets based on population hybrids, and to derive conclusions for future breeding programs. Therefore, 17 open‐pollinated varieties (OPVs) were crossed in a diallel mating design and tested together with their offspring in nine environments over 2 yr in Niger and Senegal. Genetic distances between the OPVs were evaluated with twenty microsatellite markers. Average panmictic better‐parent heterosis (PBPH) was 18% (1–47%) for panicle yield. A principal coordinate analysis based on genotyping results separated parental OPVs clearly by geographic origin. Although there was no relationship between genetic distance among OPVs and PBPH, we confirmed good combining ability among selected OPVs from Niger vs. Senegal. The identified cultivars (Nigerien CIVT, H80‐10Gr, and Taram and Senegalese Thialack 2 and Souna 3) with high combining ability are recommended for founding divergent heterotic pools targeting long‐panicle pearl millet hybrids. Our study shows the benefits of population hybrids and represents an important step to identify combining ability patterns and initial heterotic groups for WA pearl millet hybrid breeding. [ABSTRACT FROM AUTHOR]

We developed a new separation method for isolating placental vascular smooth muscle cells (PVSMCs) from a rat in this study. Our method used the magnetic force between a magnet and ferrous ferric oxide (Fe3O 4) to make the separation and extraction processes easier and more efficient. From the first to sixth generation, the cells isolated using this protocol were identified as smooth muscle cells (SMCs) by their immunoreactivity to the SMC markers and by the "hill and valley" morphology. PVSMCs were exposed to angiotensin II (1 μmol/L) and resulted in sharply increased intracellular Ca 2+ concentration. Furthermore, activation of protein kinase C (PKC) increased concomitantly with a decrease in calponin expression. These results indicate that the isolated cells had biological activity. Our method of isolating PVSMCs from rat leads to isolation of cultured cells with activity and high purity. The approach will be useful in research studies on placental vascular diseases. In this study, we described a simple and efficient method for isolating placental vascular smooth muscle cells (PVSMCs) from rat. The method used the magnetic force between a magnet and ferrous ferric oxide (Fe304) to make the separation and extraction of VSMC. The cells isolated using this protocol were identified as smooth muscle cells (SMCs) by immunoreactivity to the SMC markers and by the "hill and valley" morphology. [ABSTRACT FROM AUTHOR]

Neuropathy, or dysfunction of peripheral nerve, is one of the most common neurological manifestation in patients with diabetes mellitus (DM). DM is typically associated with a hyperglycaemic milieu, which promotes non-enzymatic glycation of proteins. Proteins with advanced glycation are known to engage a cell-surface receptor called the receptor for advanced glycation end products (RAGE). Thus, it is reasonable to assume that RAGE and its associated molecule-mediated cellular signalling may contribute to DM-induced symmetrical axonal (length-dependent) neuropathy. Of particular interest is diaphanous related formin 1 (DIAPH1), a cytoskeletal organizing molecule, which interacts with the cytosolic domain of RAGE and whose dysfunction may precipitate axonopathy/neuropathy. Indeed, it has been demonstrated that both RAGE and DIAPH1 are expressed in the motor and sensory fibres of nerve harvested from DM animal models. Although the detailed molecular role of RAGE and DIAPH1 in diabetic neurological complications remains unclear, here we will discuss available evidence of their involvement in peripheral diabetic neuropathy. Specifically, we will discuss how a hyperglycaemic environment is not only likely to elevate advanced glycation end products (ligands of RAGE) and induce a pro-inflammatory environment but also alter signalling via RAGE and DIAPH1. Further, hyperglycaemia may regulate epigenetic mechanisms that interacts with RAGE signalling. We suggest the cumulative effect of hyperglycaemia on RAGE-DIAPH1-mediated signalling may be disruptive to axonal cytoskeletal organization and transport and is therefore likely to play a key role in pathogenesis of diabetic symmetrical axonal neuropathy., (© 2021 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Aim Hyperglycaemia is an important risk factor for acute myocardial infarction. It can lead to increased induction of non-oxidative glucose pathways ( NOGPs) - polyol and hexosamine biosynthetic pathways, advanced glycation end products and protein kinase C - that may contribute to cardiovascular diseases onset. However, the precise underlying mechanisms remain poorly understood. Here we hypothesized that acute hyperglycaemia increases myocardial oxidative stress and NOGP activation resulting in cardiac dysfunction during ischaemia-reperfusion and that inhibition of, and/or shunting flux away from NOGPs [by benfotiamine ( BFT) treatment], leads to cardioprotection. Methods We employed several experimental systems: (i) Isolated rat hearts were perfused ex vivo with Krebs- Henseleit buffer containing 33 m m glucose vs. controls (11 m m glucose) ± global ischaemia and reperfusion ± BFT (first 20 min of reperfusion); (ii) Infarct size determination as per the ischaemic protocol, but with regional ischaemia and reperfusion ± BFT treatment; in separate experiments, NOGP inhibitors were also employed for (i) and (ii); and (iii) In vivo coronary ligations performed on streptozotocin-treated rats ± BFT treatment (early reperfusion). Results Acute hyperglycaemia generated myocardial oxidative stress, NOGP activation and apoptosis, but caused no impairment of cardiac function during pre-ischaemia, thereby priming hearts for later damage. Following ischaemia-reperfusion (under hyperglycaemic conditions), such effects were exacerbated together with cardiac contractile dysfunction. Moreover, inhibition of respective NOGPs and shunting away by BFT treatment (in part) improved cardiac function during ischaemia-reperfusion. Conclusion Coordinate NOGP activation in response to acute hyperglycaemia results in contractile dysfunction during ischaemia-reperfusion, allowing for the development of novel cardioprotective agents. [ABSTRACT FROM AUTHOR]

The receptor for advanced glycation end-products ( RAGE) is a pattern recognition receptor sensing endogenous stress signals associated with the development of various diseases, including diabetes, vascular complications, Alzheimer's disease and cancer. RAGE ligands include advanced glycation end-products, S100 proteins, high mobility group box 1 protein and amyloid β-peptides/fibrils. Their signalling through RAGE induces a sustained inflammation that accentuates tissue damage, thereby participating in disease progression. Receptor oligomerization appears to be a crucial parameter for the formation of active signalling complexes, although the precise mode of oligomerization remains unclear in the context of these various ligands. In the present study, we report the first crystal structure of the VC1 C2 fragment of the RAGE ectodomain. This structure provides the first description of the C2 domain in the context of the entire ectodomain and supports the observation of its conformational freedom relative to the rigid VC1 domain tandem. In addition, we have obtained a new crystal structure of the RAGE VC1 fragment. The packing in both crystal structures reveals an association of the RAGE molecules through contacts between two V domains and the physiological relevance of this homodimerization mode is discussed. Based on homology with single-pass transmembrane receptors, we also suggest RAGE dimerization through a conserved Gxxx G motif within its transmembrane domain. A multimodal homodimerization strategy of RAGE is proposed to form the structural basis for ligand-specific complex formation and signalling functions, as well as for RAGE-mediated cell adhesion. Structured digital abstract hRAGE_VC1C2 and hRAGE_VC1C2 bind by x-ray crystallography (View interaction), hRAGE_VC1 and hRAGE_VC1 bind by x-ray crystallography (View interaction) [ABSTRACT FROM AUTHOR]