Clinical, epidemiological, and therapeutic hallmarks of pyoderma gangrenosum: a case series of 35 patients.

BACKGROUND: Over the past few decades, advances in medical research and diagnostic tools have shed light on some aspects of pyoderma gangrenosum (PG). Nevertheless, the multifactorial etiology, pathogenesis, and optimal management strategies for PG need to be further investigated. To address these knowledge gaps and contribute to a better understanding of this complex dermatological disorder, we collected epidemiological, clinical, and therapeutic aspects of a case series of PG patients occurring in our department over the past 10 years. METHODS: We performed a single-centered, retrospective, observational study analyzing all cases with a diagnosis of PG observed at the Dermatology clinic of the Fondazione Policlinico A. Gemelli IRCCS Catholic University from January 1, 2013, to January 1, 2023. For each case, we retrieved demographic data, the presence of other skin and systemic conditions, and the histopathological and clinical characteristics of PG, such as clinical variant, number of lesions, disease localization, previous therapy, response to treatment, and occurrence of relapse. RESULTS: We included 35 patients, 22 females and 13 males with a mean age of 40.0 years. Twenty patients (57.1%) had multiple localizations of disease, and the most commonly involved site was the lower limbs (85.7%). The lesions were mainly associated with inflammatory bowel diseases (51.4%) and hidradenitis suppurativa (37.1%). Clinical resolution with complete re-epithelialization was achieved in 25 patients (71.4%) with an average time of 20.8 months. On average, patients who underwent therapy with biological drugs had better outcomes. CONCLUSIONS: PG is a severe, rare, and pleomorphic disease associated with a broad spectrum of conditions. Corticosteroids remain the primary first-line approach for severe forms, but using biological immunosuppressants is promising.

New Insights on the Mechanisms of Myocardial Injury in Hypertensive Patients With COVID-19.

PURPOSE: Myocardial injury is common in hypertensive patients with 2019 coronavirus disease (COVID-19). Immune dysregulation could be associated to cardiac injury in these patients, but the underlying mechanism has not been fully elucidated. METHODS: All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury. RESULTS: The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8+CD38+ mean fluorescence intensity (MFI), and percentage of CD8+ human leukocyte antigen DR isotope (HLA-DR)+ CD38-cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A)+ MFI, percentage of CD8+CD38+cells, CD8+HLA-DR+MFI, CD8+NKG2A+MFI, and percentage of CD8+HLA-DR-CD38+cells. On multivariate regression, the CD8+HLA-DR+MFI, CD8+CD38+MFI, and total lymphocyte count were associated significantly with myocardial injury. CONCLUSION: Our findings suggest that lymphopenia, CD8+CD38+MFI, and CD8+HLA-DR+MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury.

Oxygen transfer and gas holdup in airlift bioreactors assembled with helical flow promoters.

Bioreactors can perform biochemical conversions mediated by biocatalysts, such as enzymes, animal cells, plants, and microorganisms. Among several existing models, airlift bioreactors are devices with the low shear environment and good mass transfer with low energy consumption, employed in several biochemical processes. The fluid flow is enabled through air injection by the sparger located at the bioreactor base. Despite its simple geometry compared with the conventional bioreactors, airlift performance can be optimized via geometrical modifications. Therefore, the objective of this work was to evaluate the effects of the addition of helical flow promoters, positioned in the riser and/or downcomer regions of an airlift of concentric tubes measuring the volumetric oxygen coefficient (kLa) and gas holdup. The results obtained by varying the gas flow rate from 1.0 to 4.0 vvm allowed the system evaluation of oxygen transfer and gas holdup. The inclusion of helical flow promoters increased the kLa, reaching up to 23% in oxygen transfer compared to tests without helicoids and up to 14% increase in the gas holdup. The inclusion of helical flow promotors was beneficial for all gas flow rates. Thus, including these flow promoters is an effective strategy to increase the oxygen transfer rate for bioprocess optimization.

Dereplication of Cytochalasans and Octaketides in Cytotoxic Extracts of Endophytic Fungi from Casearia arborea (Salicaceae).

Endophytes have been shown to be a source of novel drug prototypes. The Casearia genus is known for presenting cytotoxic clerodane diterpenes; however, there are few reports on secondary metabolites produced by its fungal microbiota. Thus, in the present study endophytic fungi obtained from the fresh leaves of C. arborea were grown in potato dextrose broth and rice to perform a secondary metabolite prospection study. The cytotoxic profile of the crude extracts at 10 µg/mL was determined by a colorimetric assay on tumor cell lines. The endophytes producing cytotoxic extracts were identified through phylogenetic analysis and belong to Diaporthe and Colletotrichum species. Metabolites present in these extracts were organized in molecular networking format based on HRMS-MS, and a dereplication process was performed to target compounds for chromatographic purification. Metabolic classes, such as lipids, peptides, alkaloids, and polyketides were annotated, and octaketide and cytochalasin derivatives were investigated. Cytochalasin H was purified from the cytotoxic Diaporthe sp. CarGL8 extract and its cytotoxic activity was determined on human cancer cell lines A549, MCF-7, and HepG2. The data collected in the present study showed that molecular networking is useful to understand the chemical profile of complex matrices to target compounds, minimizing the cost and time spent in purification processes.

JcTI-PepI, a synthetic peptide bioinspired in the trypsin inhibitor from Jatropha curcas, presents potent inhibitory activity against C. krusei, a neglected pathogen.

Antimicrobial resistance has been increasing globally, posing a global public health risk. It has prompted the scientific community to look for alternatives to traditional drugs. Antimicrobial Peptides (AMPs) have stood out in this context because they have the potential to control infectious diseases while causing no or little harm to mammalian cells. In the present study, three peptides, JcTI-PepI, JcTI-PepII, and JcTI-PepIII, were designed and tested for antimicrobial activity based on the primary sequence of JcTI-I, a 2S albumin with trypsin inhibitory activity from Jatropha curcas. JcTI-PepI strongly inhibited C. krusei growth, and it caused severe disruptions in cellular processes and cell morphology. C. krusei cells treated with JcTI-PepI showed indicative of membrane permeabilization and overproduction of Reactive Oxygen Species. Moreover, the yeast's ability to acidify the medium was severely compromised. JcTI-PepI was also effective against pre-formed biofilm and did not harm human erythrocytes and Vero cells. Overall, these characteristics indicate that JcTI-PepI is both safe and effective against C. krusei, an intrinsically resistant strain that causes serious health problems and is frequently overlooked. It implies that this peptide has a high potential for use as a new antimicrobial agent in the future.

Catalyst-Free Click Chemistry for Engineering Chondroitin Sulfate-Multiarmed PEG Hydrogels for Skin Tissue Engineering.

The quest for an ideal biomaterial perfectly matching the microenvironment of the surrounding tissues and cells is an endless challenge within biomedical research, in addition to integrating this with a facile and sustainable technology for its preparation. Engineering hydrogels through click chemistry would promote the sustainable invention of tailor-made hydrogels. Herein, we disclose a versatile and facile catalyst-free click chemistry for the generation of an innovative hydrogel by combining chondroitin sulfate (CS) and polyethylene glycol (PEG). Various multi-armed PEG-Norbornene (A-PEG-N) with different molecular sizes were investigated to generate crosslinked copolymers with tunable rheological and mechanical properties. The crosslinked and mechanically stable porous hydrogels could be generated by simply mixing the two clickable Tetrazine-CS (TCS) and A-PEG-N components, generating a self-standing hydrogel within minutes. The leading candidate (TCS-8A-PEG-N (40 kD)), based on the mechanical and biocompatibility results, was further employed as a scaffold to improve wound closure and blood flow in vivo. The hydrogel demonstrated not only enhanced blood perfusion and an increased number of blood vessels, but also desirable fibrous matrix orientation and normal collagen deposition. Taken together, these results demonstrate the potential of the hydrogel to improve wound repair and hold promise for in situ skin tissue engineering applications.

Effectiveness of community-based burden estimation to achieve elimination of lymphatic filariasis: A comparative cross-sectional investigation in Côte d'Ivoire.

For lymphatic filariasis (LF) elimination, endemic countries must document the burden of LF morbidity (LFM). Community-based screening (CBS) is used to collect morbidity data, but evidence demonstrating its reliability is limited. Recent pilots of CBS for LFM alongside mass drug administration (MDA) in Côte d'Ivoire suggested low LFM prevalence (2.1-2.2 per 10,000). We estimated LFM prevalence in Bongouanou District, Côte d'Ivoire, using a comparative cross-sectional design. We compared CBS implemented independently of MDA, adapted from existing Ministry of Health protocols, to a population-based prevalence survey led by formally trained nurses. We evaluated the reliability of case identification, coverage, equity, and cost of CBS. CBS identified 87.4 cases of LFM per 10,000; the survey identified 47.5 (39.4-56.3; prevalence ratio [PR] 1.84; 95% CI 1.64-2.07). CBS identified 39.7 cases of suspect lymphoedema per 10,000; the survey confirmed 35.1 (29.2-41.5) filarial lymphoedema cases per 10,000 (PR 1.13 [0.98-1.31]). CBS identified 96.5 scrotal swellings per 10,000; the survey found 91.3 (83.2-99.8; PR 1.06 [0.93-1.21]); including 33.9 (27.7-38.8) filarial hydrocoele per 10,000 (PR of suspect to confirmed hydrocele 2.93 [2.46-3.55]). Positive predictive values for case identification through CBS were 65.0% (55.8-73.5%) for filarial lymphoedema; 93.7% (89.3-96.7%) for scrotal swellings; and 34.0% (27.3-41.2%) for filarial hydrocoele. Households of lower socioeconomic status and certain minority languages were at risk of exclusion. Direct financial costs were $0.17 per individual targeted and $69.62 per case confirmed. Our community-based approach to LFM burden estimation appears scalable and provided reliable prevalence estimates for LFM, scrotal swellings and LF-lymphoedema. The results represent a step-change improvement on CBS integrated with MDA, whilst remaining at programmatically feasible costs. Filarial hydrocoele cases were overestimated, attributable to the use of case definitions suitable for mass-screening by informal staff. Our findings are broadly applicable to countries aiming for LF elimination using CBS. The abstract is available in French in the S1 File.

Green coffee extract attenuates Parkinson's-related behaviors in animal models.

Epidemiological studies have shown an inverse association between coffee consumption and the development of Parkinson's disease (PD). The effects of the oral treatment with green (non-roasted) coffee extracts (CE, 100 or 400 mg/kg) and caffeine (31.2 mg/kg) were evaluated on catalepsy induced by haloperidol in mice, and unilateral 6-OHDA lesion of medial forebrain bundle (MFB) or striatum in rats. Also, the in vitro antioxidant activity and the monoamine levels in the striatum were investigated. CE presented a mild antioxidant activity in vitro and its administration decreased the catalepsy index. CE at the dose of 400 mg/kg induced ipsilateral rotations 14 days after lesion; however, chronic 30-day CE and caffeine treatments did not interfere with the animals' rotation after apomorphine or methamphetamine challenges in animals with MFB lesion, nor on monoamines levels. Furthermore, CE and caffeine were effective in inhibiting the asymmetry between ipsilateral and contralateral rotations induced by methamphetamine and apomorphine in animals with lesion in the striatum but did not avoid the monoamines depletion. These results indicate that CE components indirectly modulate dopaminergic transmission, suggesting a pro-dopaminergic action of CE, and further investigation must be conducted to elucidate the mechanisms of action and the possible neuroprotective role in PD.

Computational approach, scanning electron and fluorescence microscopies revealed insights into the action mechanisms of anticandidal peptide Mo-CBP3-PepIII.

AIMS: The Candida genus is composed of opportunistic pathogens that threaten public health. Given the increase in resistance to current drugs, it is necessary to develop new drugs to treat infections by these pathogens. Antimicrobial peptides are promising alternative molecules with low cost, broad action spectrum and low resistance induction. This study aimed to clarify the action mechanisms of synthetic peptides against Candida albicans. MAIN METHODS: The mode of action of the anticandidal peptides Mo-CBP3-PepIII were analyzed through molecular dynamics and quantum biochemistry methods against Exo-ß-1,3-glucanase (EXG), vital to cell wall metabolism. Furthermore, scanning electron (SEM) and fluorescence (FM) microscopies were employed to corroborate the in silico data. KEY FINDINGS: Mo-CBP3-PepIII strongly interacted with EXG (-122.2 kcal mol-1) at the active site, higher than the commercial inhibitor pepstatin. Also, molecular dynamics revealed the insertion of Mo-CBP3-PepIII into the yeast membrane. SEM analyses revealed that Mo-CBP3-PepIII induced cracks and scars of the cell wall and FM analyses confirmed the pore formation on the Candida membrane. SIGNIFICANCE: Mo-CBP3-PepIII has strong potential as a new drug with a broad spectrum of action, given its different mode of action compared to conventional drugs.

Synthetic peptides against Trichophyton mentagrophytes and T. rubrum: Mechanisms of action and efficiency compared to griseofulvin and itraconazole.

AIMS: According to the WHO, 20-25% of people worldwide are affected by skin infections caused by dermatophytes, such as those of the Trichophyton genus. Additionally, several dermatophytes have developed resistance to drugs such as griseofulvin and itraconazole. This study tested 2S albumins-derived antimicrobial peptides (AMPs) as alternative antidermatophytic molecules. MAIN METHODS: Membrane pore formation assays, tests to detect overproduction of ROS, scanning electron microscopy (SEM) and fluorescence microscopy (FM) were carried out to provide insight into the mechanisms of antidermatophytic action. KEY FINDINGS: All AMPs (at 50 µg mL-1) tested reduced the mycelial growth of T. mentagrophytes and T. rubrum by up to 95%. In contrast, using a concentration 20-fold higher, griseofulvin only inhibited T. mentagrophytes by 35%, while itraconazole was not active against both dermatophytes. Scanning electron and fluorescence microscopies revealed that the six AMPs caused severe damage to hyphal morphology by inducing cell wall rupture, hyphal content leakage, and death. Peptides also induced membrane pore formation and oxidative stress by overproduction of ROS. Based on the stronger activity of peptides than the commercial drugs and the mechanism of action, all six peptides have the potential to be either employed as models to develop new antidermatophytic drugs or as adjuvants to existing ones. SIGNIFICANCE: The synthetic peptides are more efficient than conventional drug to treat infection caused by dermatophytes being potential molecules to develop new drugs.

Antidermatophytic activity of synthetic peptides: Action mechanisms and clinical application as adjuvants to enhance the activity and decrease the toxicity of Griseofulvin.

BACKGROUND: Dermatophytes belonging to the Trichophyton genus are important human pathogens, but they have developed resistance to griseofulvin, the most common antifungal drug used to treat dermatophytosis. OBJECTIVE: This study was aimed to evaluate the antidermatophytic activity of synthetic peptides, as well as mechanisms of action and synergistic effect with griseofulvin. METHODS: Scanning electron microscopy (SEM), atomic force microscopy (AFM) and fluorescence microscopy (FM) were employed to understand the activity and the mechanism of action of peptides. RESULTS: Here we report that synthetic peptides at 50 µg/mL, a concentration 20-fold lower than griseofulvin, reduced the microconidia viability of T. mentagrophytes and T. rubrum by 100%, whereas griseofulvin decreased their viability by only 50% and 0%, respectively. The action mechanism of peptides involved cell wall damage, membrane pore formation and loss of cytoplasmic content. Peptides also induced overproduction of reactive oxygen species (ROS) and enhanced the activity of griseofulvin 10-fold against both fungi, suggesting synergistic effects, and eliminated the toxicity of this drug to human erythrocytes. Docking analysis revealed ionic and hydrophobic interactions between peptides and griseofulvin, which may explain the decline of griseofulvin toxicity when mixed with peptides. CONCLUSION: Therefore, our results strongly suggest six peptides with high potential to be employed alone as new drugs or as adjuvants to enhance the activity and decrease the toxicity of griseofulvin.

Anticandidal activity of synthetic peptides: Mechanism of action revealed by scanning electron and fluorescence microscopies and synergism effect with nystatin.

Candida albicans has emerged as a major public health problem in recent decades. The most important contributing factor is the rapid increase in resistance to conventional drugs worldwide. Synthetic antimicrobial peptides (SAMPs) have attracted substantial attention as alternatives and/or adjuvants in therapeutic treatments due to their strong activity at low concentrations without apparent toxicity. Here, two SAMPs, named Mo-CBP3 -PepI (CPAIQRCC) and Mo-CBP3 -PepII (NIQPPCRCC), are described, bioinspired by Mo-CBP3 , which is an antifungal chitin-binding protein from Moringa oleifera seeds. Furthermore, the mechanism of anticandidal activity was evaluated as well as their synergistic effects with nystatin. Both peptides induced the production of reactive oxygen species (ROS), cell wall degradation, and large pores in the C. albicans cell membrane. In addition, the peptides exhibited high potential as adjuvants because of their synergistic effects, by increasing almost 50-fold the anticandidal activity of the conventional antifungal drug nystatin. These peptides have excellent potential as new drugs and/or adjuvants to conventional drugs for treatment of clinical infections caused by C. albicans.

Gene expression during development and overexpression after Cercospora kikuchii and salicylic acid challenging indicate defensive roles of the soybean toxin.

KEY MESSAGE: SBTX has defensive role against C. kikuchii, and therefore, its constituent genes SBTX17 and SBTX27 are promising candidates to engineer pathogen resistant plants. Soybean (Glycine max [L.] Merr.) is economically the most important legume crop in the world. Its productivity is strongly affected by fungal diseases, which reduce soybean production and seed quality and cause losses of billions of dollars worldwide. SBTX is a protein that apparently takes part in the defensive chemical arsenal of soybean against pathogens. This current study provides data that reinforce this hypothesis. Indeed, SBTX inhibited in vitro the mycelial growth of Cercospora kikuchii, it is constitutively located in the epidermal region of the soybean seed cotyledons, and it is exuded from mature imbibed seeds. Moreover, RT-qPCR analysis of the SBTX associated genes, SBTX17 and SBTX27, which encode for the 17 and 27 kDa polypeptide chains, showed that both genes are expressed in all studied plant tissues during the soybean development, with the highest levels found in the mature seeds and unifoliate leaves. In addition, to assess a local response of the soybean secondary leaves from 35-day-old plants, they were inoculated with C. kikuchii and treated with salicylic acid. It was verified using RT-qPCR that SBTX17 and SBTX27 genes overexpressed in leaves compared to controls. These findings strongly suggest that SBTX has defensive roles against C. kikuchii. Therefore, SBTX17 and SBTX27 genes are promising candidates to engineer pathogen resistant plants.

RcAlb-PepII, a synthetic small peptide bioinspired in the 2S albumin from the seed cake of Ricinus communis, is a potent antimicrobial agent against Klebsiella pneumoniae and Candida parapsilosis.

Antimicrobial peptides (AMPs) are important constituents of the innate immunity system of all living organisms. They participate in the first line of defense against invading pathogens such as viruses, bacteria, and fungi. In view of the increasing difficulties to treat infectious diseases due to the emergence of antibiotic-resistant bacterial strains, AMPs have great potential to control infectious diseases in humans and animals. In this study, two small peptides, RcAlb-PepI and RcAlb-PepII, were designed based on the primary structure of Rc-2S-Alb, a 2S albumin from the seed cake of Ricinus communis, and their antimicrobial activity assessed. RcAlb-PepII strongly inhibited the growth of Klebsiella pneumoniae and Candida parapsilosis, and induced morphological alterations in their cell surface. C. parapsilosis exposed to RcAlb-PepII presented higher cell membrane permeabilization and elevated content of reactive oxygen species. RcAlb-PepII also degraded and reduced the biofilm formation in C. parapsilosis and in K. pneumonia cells. Experimentally, RcAlb-PepII was not hemolytic and had low toxicity to mammalian cells. These are advantageous characteristics, which suggest that RcAlb-PepII is safe and apparently effective for its intended use and has great potential for the future development of an antimicrobial agent with the ability to kill or inhibit K. pneumoniae and C. parapsilosis cells.

Scanning electron microscopy reveals deleterious effects of Moringa oleifera seed exuded proteins on root-knot nematode Meloidogyne incognita eggs.

Plant seeds can exudate active molecules with inhibitory effects against several soil pathogens, including nematodes. This study aimed to characterize and evaluate the nematicidal properties against Meloidogyne incognita of exuded proteins from Moringa oleifera seeds. M. oleifera seeds were soaked in distilled water, and exudates were harvested and analyzed for the presence of defense proteins and anthelmintic activity. Enzymatic assays revealed the existence of PR-proteins such as ß-1,3-glucanases (0.18 ± 0.003 nkatal mg-1 of protein), chitinases (0.22 ± 0.004 nkatal mg-1 of protein), proteases (261.30 ± 6.405 AU mg-1 of protein min-1), serine (190.30 ± 5.574 IA mg-1 of protein) and cysteine (231.70 ± 0.923 IA mg-1 of protein), protease inhibitors. The exuded proteins presented ovicidal activity and caused 100% mortality of second-stage juveniles (J2s). Scanning electron microscopy (SEM) revealed deleterious effects on M. incognita eggs, such as invaginations, cracks, scratched surface, and loss of internal content. These findings confirm the presence of anthelmintic proteins in M. oleifera seed exudate, possibly involved in plant defense during seed germination. Besides this, the exuded proteins exhibited strong biotechnological potential for use in the biocontrol of M. incognita infections, which are responsible for millions of dollars in staple crop losses every year.

ClTI, a Kunitz trypsin inhibitor purified from Cassia leiandra Benth. seeds, exerts a candidicidal effect on Candida albicans by inducing oxidative stress and necrosis.

Cassia leiandra is an Amazonian plant species that is used popularly for the treatment of mycoses. Recently, a protease inhibitor, named ClTI, with insecticidal activity against Aedes aegypti, was purified from the mature seeds of C. leiandra. In this work, we show that ClTI has antifungal activity against Candida species and describe its mode of action towards Candida albicans. This study is relevant because the nosocomial infections caused by Candida species are a global public health problem that, together with the growing resistance to current drugs, has increased the urgency of the search for new antifungal compounds. ClTI inhibited the growth of Candida albicans, Candida tropicalis, Candida parapsilosis, and Candida krusei. However, ClTI was more potent against C. albicans. The candidicidal mode of action of ClTI on C. albicans involves enhanced cell permeabilization, alteration of the plasma membrane proton-pumping ATPase function (H+ -ATPase), induction of oxidative stress, and DNA damage. ClTI also exhibited antibiofilm activity and non-cytotoxicity to mammalian cells. These results indicate that ClTI is a promising candidate for the future development of a new, natural, and safe agent for the treatment of infections caused by C. albicans.

Gene expression and spatiotemporal localization of antifungal chitin-binding proteins during Moringa oleifera seed development and germination.

MAIN CONCLUSION: Chitin-binding proteins behave as storage and antifungal proteins in the seeds of Moringa oleifera. Moringa oleifera is a tropical multipurpose tree. Its seed constituents possess coagulant, bactericidal, fungicidal, and insecticidal properties. Some of these properties are attributed to a group of polypeptides denominated M. oleifera chitin-binding proteins (in short, Mo-CBPs). Within this group, Mo-CBP2, Mo-CBP3, and Mo-CBP4 were previously purified to homogeneity. They showed high amino acid similarity with the 2S albumin storage proteins. These proteins also presented antimicrobial activity against human pathogenic yeast and phytopathogenic fungi. In the present study, the localization and expression of genes that encode Mo-CBPs and the biosynthesis and degradation of the corresponding proteins during morphogenesis and maturation of M. oleifera seeds at 15, 30, 60, and 90 days after anthesis (DAA) and germination, respectively, were assessed. The Mo-CBP transcripts and corresponding proteins were not detected at 15 and 30 days after anthesis (DAA). However, they accumulated at the latter stages of seed maturation (60 and 90 DAA), reaching the maximum level at 60 DAA. The degradation kinetics of Mo-CBPs during seed germination by in situ immunolocalization revealed a reduction in the protein content 48 h after sowing (HAS). Moreover, Mo-CBPs isolated from seeds at 60 and 90 DAA prevented the spore germination of Fusarium spp. Taken together, these results suggest that Mo-CBPs play a dual role as storage and defense proteins in the seeds of M. oleifera.

Insight into epileptic and physiological déjà vu: from a multicentric cohort study.

BACKGROUND AND PURPOSE: The presence of a continuum between physiological déjà vu (DV) and epileptic DV is still not known as well as epidemiological data in the Italian population. The aim was to identify the epidemiological distribution of DV in Italy, and secondly to look for specific features of DV able to discriminate between epileptic and non-epileptic DV. METHODS: In all, 1000 individuals, 543 healthy controls (C) (313 women; age 40 ± 15 years) and 457 patients with epilepsy (E) (260 women; age 39 ± 14 years), were prospectively recruited from 10 outpatient neurological clinics throughout Italy. All populations were screened using the Italian Inventory for Déjà Vu Experiences Assessment (I-IDEA) test and E and pairwise C underwent a comprehensive epilepsy interview. RESULTS: Of E, 69% stated that they experienced 'recognition' and 13.2% reported that this feeling occurred from a few times a month to at least weekly (versus 7.7% of the control group). Furthermore, a greater percentage of E (6.8% vs. 2.2%) reported that from a few times a month to at least weekly they felt that it seemed as though everything around was not real. In E, the feeling of recognition raised fright (22.3% vs. 13.2%) and a sense of oppression (19.4% vs. 9.4%). A fifth of E felt recognition during epileptic seizures. CONCLUSION: Only E regardless of aetiology firmly answered that they had the feeling of recognition during an epileptic seizure; thus question 14 of the I-IDEA test part 2 discriminated E from C. Paranormal activity, remembering dreams and travel frequency were mostly correlated to DV in E suggesting that the visual-memory network might be involved in epileptic DV.

Mo-CBP3-PepI, Mo-CBP3-PepII, and Mo-CBP3-PepIII are synthetic antimicrobial peptides active against human pathogens by stimulating ROS generation and increasing plasma membrane permeability.

The efficiency of current antimicrobial drugs is noticeably decreasing and thus the development of new treatments is necessary. Natural and synthetic antimicrobial peptides (AMPs) have attracted great attention as promising candidates. Inspired on Mo-CBP3, an antimicrobial protein from Moringa oleifera seeds, we designed and synthesized three AMPs named Mo-CBP3-PepI, Mo-CBP3-PepII, and Mo-CBP3-PepIII. All these three peptides inhibited the growth of Candida species and pathogenic bacteria, penetrate into microbial cells, but none is hemolytic or toxic to human cells. Mo-CBP3-PepIII, particularly, showed the strongest antimicrobial activity against Staphylococcus aureus and Candida species, important human pathogens. Additionally, Mo-CBP3-PepIII did not exhibit hemolytic or toxic activity to mammalian cells, but increased Staphylococcus aureus plasma membrane permeabilization. In Candida parapsilosis, Mo-CBP3-PepIII induced pore formation in the plasma membrane and overproduction of reactive oxygen species. Bioinformatics analysis suggested that Mo-CBP3-PepIII is resistant to pepsin digestion and other proteolytic enzymes present in the intestinal environment, which opens the possibility of oral delivery in future treatments. Together, these results suggest that Mo-CBP3-PepIII has great potential as an antimicrobial agent against the bacterium S. aureus and the fungi C. parapsilosis.

Buruli ulcer in southern Côte D'ivoire: dynamic schemes of perception and interpretation of modes of transmission.

Buruli ulcer (BU) belongs to the group of neglected tropical diseases and constitutes a public health problem in many rural communities in Côte d'Ivoire. The transmission patterns of this skin infection are poorly defined, hence the current study aimed to contribute to the understanding, perceptions and interpretations of its mode of transmission using a socio-environmental approach. Social and environmental risk factors that may expose people to infection, and the dynamics of local transfer of knowledge and practices related to BU, were assessed in two endemic locations in southern Côte d'Ivoire, i.e. Taabo and Daloa. Data were generated by the administration of a household questionnaire (N=500) between February and June 2012 to assess how the population perceived transmission of BU, focus group discussions with local communities (N=8) to analyse ideologies regarding transmission patterns and semi-structured interviews with patients or their parents, former BU patients and traditional healers (N=30). The interviewees' empirical knowledge of the disease was found to be close to its biomedical description. Their aetiological perception of the disease was linked to natural (e.g. dirty water, insects) and supernatural (e.g. witchcraft, fate) causes. Some informants attributed the spread of the disease to recently immigrated neighbouring communities whose arrival coincided with an increase in reported BU cases. However, the general consensus seemed to be that the main mode of transmission was contact with infested soil or ulcerated wounds. The participants were aware that BU was a socio-environmental problem in these endemic areas, offering a good starting point for educational campaigns for at-risk communities. Buruli ulcer control programmes should therefore include educational campaigns and Water, Sanitation and Hygiene (WASH) interventions for those at risk in affected communities.