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1.
Science ; 385(6716): eadm7966, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39325875

ABSTRACT

We report the discovery of MED6-189, an analog of the kalihinol family of isocyanoterpene natural products that is effective against drug-sensitive and drug-resistant Plasmodium falciparum strains, blocking both asexual replication and sexual differentiation. In vivo studies using a humanized mouse model of malaria confirm strong efficacy of the compound in animals with no apparent hemolytic activity or toxicity. Complementary chemical, molecular, and genomics analyses revealed that MED6-189 targets the parasite apicoplast and acts by inhibiting lipid biogenesis and cellular trafficking. Genetic analyses revealed that a mutation in PfSec13, which encodes a component of the parasite secretory machinery, reduced susceptibility to the drug. Its high potency, excellent therapeutic profile, and distinctive mode of action make MED6-189 an excellent addition to the antimalarial drug pipeline.


Subject(s)
Antimalarials , Apicoplasts , Diterpenes , Malaria, Falciparum , Plasmodium falciparum , Animals , Humans , Mice , Antimalarials/chemistry , Antimalarials/pharmacology , Apicoplasts/drug effects , Apicoplasts/metabolism , Disease Models, Animal , Drug Resistance/genetics , Malaria, Falciparum/drug therapy , Malaria, Falciparum/parasitology , Mutation , Plasmodium falciparum/drug effects , Plasmodium falciparum/genetics , Protozoan Proteins/metabolism , Protozoan Proteins/genetics , Diterpenes/chemistry , Diterpenes/pharmacology
2.
Pathogens ; 13(8)2024 Aug 17.
Article in English | MEDLINE | ID: mdl-39204297

ABSTRACT

Sub-Saharan Africa, with its hot and humid climate, is a conducive zone for tick proliferation. These vectors pose a major challenge to both animal and human health in the region. However, despite the relevance of emerging diseases and evidence of tick-borne disease emergence, very few studies have been dedicated to investigating zoonotic pathogens transmitted by ticks in this area. To raise awareness of the risks of tick-borne zoonotic diseases in sub-Saharan Africa, and to define a direction for future research, this systematic review considers the trends of research on tick-borne bacteria, parasites, and viruses from 2012 to 2023, aiming to highlight the circulation of these pathogens in ticks, cattle, sheep, goats, and humans. For this purpose, three international databases were screened to select 159 papers fitting designed inclusion criteria and used for qualitative analyses. Analysis of these studies revealed a high diversity of tick-borne pathogens in sub-Saharan Africa, with a total of 37 bacterial species, 27 parasite species, and 14 viruses identified. Among these, 27% were zoonotic pathogens, yet only 11 studies investigated their presence in humans. Furthermore, there is growing interest in the investigation of bacteria and parasites in both ticks and ruminants. However, research into viruses is limited and has only received notable interest from 2021 onwards. While studies on the detection of bacteria, including those of medical interest, have focused on ticks, little consideration has been given to these vectors in studies of parasites circulation. Regarding the limited focus on zoonotic pathogens transmitted by ticks, particularly in humans, despite documented cases of emerging zoonoses and the notable 27% proportion reported, further efforts should be made to fill these gaps. Future studies should prioritize the investigation of zoonotic pathogens, especially viruses, which represent the primary emerging threats, by adopting a One Health approach. This will enhance the understanding of their circulation and impact on both human and animal health. In addition, more attention should be given to the risk factors/drivers associated to their emergence as well as the perception of the population at risk of infection from these zoonotic pathogens.

3.
Parasit Vectors ; 17(1): 365, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39198870

ABSTRACT

BACKGROUND: Acaricide resistance in cattle ticks is a significant concern in (sub)tropical regions, particularly Brazil. The Larval Packet Test (LPT) is the standard laboratory bioassay for resistance diagnosis, which requires triplicates of seven acaricidal dilutions plus controls to cover larval mortalities ranging between 0 and 100%. The value of the LPT lies in providing resistance ratios based on the ratio between the LC50 calculated with potentially resistant and susceptible ticks. However, LC50 ratios are difficult to translate into practical advice for farmers. Moreover, LPT requires laboratory facilities to maintain susceptible tick colonies, and it takes 6 weeks to obtain the larvae to be tested by LPT derived from engorged female ticks collected from cattle in the field. Our novel approach was twofold: first, we upgraded the LPT to the Resistance Intensity Test (RIT) by adopting the latest WHO guidelines for resistance detection in mosquitoes, which combines a 1 × recommended dose with 5 × and 10 × concentrated doses to reveal low, moderate and high resistance intensity, respectively. This reduced the number of test papers and tick larvae and, more importantly, provided relevant information on the resistance level. Our second innovative step was to abolish testing larvae entirely and expose partly engorged adult ticks to the same acaricidal doses immediately after removing them from cattle in the field. This resulted in the Rapid Tick exposure Test (RaTexT®), wherein partly engorged adult ticks were exposed to an acaricide-impregnated, specially designed matrix providing test results within 24 h. This approach directly compared resistance detection in tick larvae in the RIT with resistance in adult ticks in RaTexT®. METHODS: Laboratory validation was conducted in Brazil with resistant and susceptible colonies of Rhipicephalus microplus ticks. For field validation, adult R. microplus ticks collected from different cattle farms in Brazil were evaluated for resistance to RaTexT®, and the results regarding their larval progenies were compared with those for the RIT. Partly engorged adult ticks derived from cattle infested with laboratory and field strains of R. microplus were exposed to deltamethrin in RaTexT® containers, which contained six rows of four interconnected compartments, accommodating five to eight semi-engorged female ticks with a preferred size ranging between 5 and 8 mm. The corresponding larvae of each strain were exposed in the RIT to the same deltamethrin concentrations in filter papers. RESULTS: In RaTexT®, mortality in adult ticks from a resistant strain of R. microplus from Seropédica in Brazil was 38.4%, 54.2% and 75.0% at the 1 ×, 5 × and 10 × doses of deltamethrin, respectively. In RIT, mortality of larvae from the same resistant strain was 2.0%, 4.9% and 19.5% at 1 ×, 5 × and 10 × doses, respectively. The results of RaTexT® and RIT agreed since both tests identified a high level of resistance based on a cut-off of 90% mortality. In RaTexT®, mortality of adult ticks from a susceptible strain originating from Porto Alegre was 73.8%, 92.9% and 97.6% at the 1 ×, 5 × and 10 × doses, respectively. In RIT, mortality of larvae from the susceptible strain was 95.2%, 95.2% and 96.8% at the 1 ×, 5 × and 10 × doses, respectively. Interestingly, both tests identified a low number of unexpected resistant individuals in the susceptible strain since the mortality of neither larvae nor adults reached 100%. This effect remained unnoticed in the LPT, wherein a resistance ratio of 159.5 was found based on the LC50 of the resistant strain divided by the LC50 of the susceptible strain. Next, RaTexT® was compared with RIT using adult and larval ticks derived from three field strains of R. microplus in Brazil. RaTexT® detected high levels of resistance to deltamethrin in adult ticks in all strains, which was confirmed in larvae tested by the RIT. Both tests agreed on the same resistance level with significantly lower mortality rates in larvae than in adult ticks. CONCLUSIONS: RaTexT® is a novel rapid pen-site test for detecting acaricide resistance in adult livestock ticks. It potentially replaces laborious tests using larval ticks and provides results within 24 h relevant to acaricide resistance management of livestock ticks.


Subject(s)
Acaricides , Larva , Rhipicephalus , Tick Infestations , Animals , Rhipicephalus/drug effects , Acaricides/pharmacology , Brazil/epidemiology , Larva/drug effects , Cattle , Female , Tick Infestations/veterinary , Cattle Diseases/parasitology , Drug Resistance , Biological Assay/methods , Pyrethrins/pharmacology , Nitriles
4.
J Evid Based Integr Med ; 29: 2515690X241251558, 2024.
Article in English | MEDLINE | ID: mdl-38689490

ABSTRACT

Liver cancer is the most common cancer among males in Africa. The disease has a poor prognosis and its treatment is associated with toxicity and resistance. For this reason, numerous herbal combinations are being subjected to anticancer screening to circumvent the shortcomings of the conventional anticancer drugs. In the current study, the in vivo anti-cancer effects of the chloroform root extract of the herb, Clausena excavata Burm were investigated. Liver cancer was induced in mice by a single intraperitoneal injection of diethylnitrosamine (DEN) followed by oral administration of the promoter of carcinogenesis, 2-aminoacetyl fluorine that was mixed with the mice feed. The cytotoxicity of the root extract of C. excavata on liver cancer cells was investigated using liver enzyme, histology, DNA fragmentation and caspases assays. Real time qPCR was conducted to evaluate the effect of the extract on apoptotic genes. The findings revealed that the extract of C. excavata significantly decreased the progression of hepatocarcinogenesis and the toxicity-induced production of the liver enzymes, alanine and aspartate aminotransferases. The histological analyses of the liver tissues revealed evidence of apoptotic cell death. The extract also provoked significant (p < .05) expressions of caspase 9 protein and gene as well as other apoptotic genes (P53, P27, Apaf-1, cytochrome C, bax and bid). Therefore, we postulate that the chloroform root extract of C. excavata induces apoptosis of liver cancer in mice.


Subject(s)
Chloroform , Liver , Carcinoma, Hepatocellular/chemically induced , Plant Roots/chemistry , Liver/drug effects , Liver/metabolism , Liver/pathology , Clausena , Diethylamines/toxicity , Antineoplastic Agents, Phytogenic/pharmacology
5.
BMC Sports Sci Med Rehabil ; 16(1): 75, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38566116

ABSTRACT

BACKGROUND: Researchers have highlighted the importance of early access to concussion care within one week of injury in reducing recovery times. However, a persisting question for concussion researchers is "just how early is important?" The purpose of this study was to examine differences in recovery time as predicted by the number of days elapsed since injury (DSI) to initial evaluation among patients who had access to a specialty concussion clinic within seven days. We hypothesized that DSI group membership, even within seven days, would significantly predict risk of protracted recovery (i.e., beyond 21 days). METHODS: In this archival study, retrospective data were gathered from electronic medical records between September 2020 to March 2022. Records of participants between ages 12-18, those diagnosed with a sports-related concussion based on initial clinic visit diagnosis by a medical provider and those who established care within seven days of injury at a large pediatric specialty concussion clinic were examined. Participants were divided into three DSI groups (patients seen in < 48 h: "acute", patients seen between 49 h < and < 96 h: "sub-acute", and patients seen between 97 < and < 168 h: "post-acute"). A general linear model was constructed to examine relationships between relevant concussion factors (e.g., Post Concussion Scale Score, neurodevelopmental history, psychiatric history, concussion history, migraine history, overall VOMS change score, cognitive testing, sex, age, race, and ethnicity) that were either significant in the preliminary analysis or in clinical judgement and recovery time. Adjusted odds ratios (OR) were derived from a binary logistic regression model, in which recovery time was normal (≤ 21 recovery days) or protracted (> 21 recovery days). RESULTS: A total of 856 participants were eligible. Adolescents in the acute group (M = 15.12, SD = 8.04) had shorter recovery times in days compared to those in the sub-acute (M = 17.98, SD = 10.18) and post-acute (M = 21.12, SD = 10.12; F = 26.00, p < .001) groups. Further, participants in the acute (OR = 4.16) and sub-acute (OR = 1.37) groups who accessed specialty concussion clinics within 48 h were 4 times more likely to have a normal recovery and recovered approximately 6 days faster than the post-acute care group. CONCLUSIONS: Earlier concussion care access predicted recovery times and was associated with lower risk for protracted recovery.

7.
Viruses ; 16(2)2024 02 03.
Article in English | MEDLINE | ID: mdl-38400020

ABSTRACT

This study aimed at investigating the genetic lineages of peste des petits ruminants virus (PPRV) currently circulating in Burkina Faso. As part of PPR surveillance in 2021 and 2022, suspected outbreaks in different regions were investigated. A risk map was produced to determine high-risk areas for PPR transmission. Based on alerts, samples were obtained from three regions and all sampled localities were confirmed to fall within PPR high risk areas. We collected swab samples from the eyes, mouth, and nose of sick goats. Some tissue samples were also collected from dead animals suspected to be infected by PPRV. In total, samples from 28 goats were analysed. Virus confirmation was performed with RT-PCR amplification targeting the nucleocapsid (N) gene. Partial N gene sequencing (350 bp) was carried out using the RT-PCR products of positives samples to characterise the circulating lineages. Eleven sequences, including ten new sequences, have been obtained. Our study identified the presence of the PPRV lineage IV in the three studied regions in Burkina Faso with a genetic heterogeneity recorded for the sequences analysed. Previously published data and results of this study suggest that PPRV lineage IV seems to be replacing lineage II in Burkina Faso.


Subject(s)
Goat Diseases , Peste-des-Petits-Ruminants , Peste-des-petits-ruminants virus , Animals , Peste-des-petits-ruminants virus/genetics , Peste-des-Petits-Ruminants/epidemiology , Burkina Faso/epidemiology , Molecular Epidemiology , Goat Diseases/epidemiology , Phylogeny , Ruminants , Goats
8.
Front Pediatr ; 12: 1207609, 2024.
Article in English | MEDLINE | ID: mdl-38333086

ABSTRACT

Background: There is an increasing consensus on the relevance of musculoskeletal fitness for health throughout the life cycle, requiring evaluation approaches and description of results capable of characterizing different age groups and body sizes. This study aimed to describe the musculoskeletal fitness of young Portuguese people aged 10-18 through handgrip strength (HGS) and vertical jump power (VJP) and investigate differences between the sexes. Methods: The sample included 736 participants (359 girls recruited from schools. HGS (kg) was assessed using a handheld dynamometer, and VJP (W) was assessed using a force platform; both measurements were standardized for body mass. Results: Higher HGS and VJP were observed in boys than in girls from 13 years old (13 years: p ≤ 0.05; 14-18 years: p ≤ 0.001), with no significant differences before this age. The percentile distributions of HGS and VJP are described for each sex using the lambda, mu, sigma (LMS) method. The pattern of development of these variables as a function of age is presented. Conclusions: Handgrip strength and vertical jump power show differences between the sexes from 13 years of age and similar trajectories to populations in other countries in the same age group.

9.
Article in English | MEDLINE | ID: mdl-38073329

ABSTRACT

OBJECTIVE: Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system. We present a case study of a 21-year-old African man with an isolated NCC lesion to the left middle frontal gyrus, which is also known as the dorsolateral prefrontal cortex (dlPFC). METHOD: A neuropsychological evaluation was requested by the patient's inpatient psychiatry team regarding worsening attention and depressive symptoms approximately 6 months after NCC diagnosis and treatment. RESULTS: Neuropsychological findings revealed deficits in the aspects of executive functioning, attention, working memory, and significant depressive symptoms. CONCLUSION: To our knowledge, this is the first case study of its kind demonstrating deficits in cognitive functioning consistent with the dlPFC lesion location. Sociocultural and linguistic considerations, clinical findings, and limitations are discussed.

10.
bioRxiv ; 2023 Nov 22.
Article in English | MEDLINE | ID: mdl-38045341

ABSTRACT

Here we report the discovery of MED6-189, a new analogue of the kalihinol family of isocyanoterpene (ICT) natural products. MED6-189 is effective against drug-sensitive and -resistant P. falciparum strains blocking both intraerythrocytic asexual replication and sexual differentiation. This compound was also effective against P. knowlesi and P. cynomolgi. In vivo efficacy studies using a humanized mouse model of malaria confirms strong efficacy of the compound in animals with no apparent hemolytic activity or apparent toxicity. Complementary chemical biology, molecular biology, genomics and cell biological analyses revealed that MED6-189 primarily targets the parasite apicoplast and acts by inhibiting lipid biogenesis and cellular trafficking. Genetic analyses in P. falciparum revealed that a mutation in PfSec13, which encodes a component of the parasite secretory machinery, reduced susceptibility to the drug. The high potency of MED6-189 in vitro and in vivo, its broad range of efficacy, excellent therapeutic profile, and unique mode of action make it an excellent addition to the antimalarial drug pipeline.

11.
Exp Parasitol ; 255: 108643, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37949426

ABSTRACT

The cattle tick Rhipicephalus microplus affects animal production economically by reducing weight gain and milk production and causing diseases, such as babesiosis and anaplasmosis. Using synthetic acaricides to reduce their incidence has caused the emergence of resistant tick populations. The present study aimed to assess the in vitro acaricidal activity of combinations of essential oils (EOs) from Ocimum americanum, Ocimum gratissimum, and Lippia multiflora against R. microplus larvae. In fact, numerous biological properties have been reported on EOs from these three plants, including acaricidal properties. Hence, a larval immersion test was performed using a population of R. microplus resistant to synthetic acaricides used in Burkina Faso. Results revealed that EO from O. gratissimum was the most effective on R. microplus larvae with LC50 and LC90 values at 10.36 and 15.51 mg/mL, respectively. For EO combinations, the most significant synergistic effect was obtained by combination 6 (1/3 O. americanum + 2/3 O. gratissimum +1/6 L. multiflora), with a combination index value of 0.44. All combinations presented dose reduction index >1, indicating a favorable dose reduction. According to the literature, this is the first study to determine the combination effect of EOs from the abovementioned plants in controlling R. microplus activity in vitro. Thus, the combination of these EOs is an alternative to control the resistant populations of invasive cattle ticks.


Subject(s)
Acaricides , Cattle Diseases , Oils, Volatile , Rhipicephalus , Tick Infestations , Animals , Cattle , Oils, Volatile/pharmacology , Plant Oils/pharmacology , Acaricides/pharmacology , Burkina Faso , Larva , Tick Infestations/prevention & control , Tick Infestations/veterinary , Cattle Diseases/prevention & control
12.
Vet Parasitol ; 324: 110059, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37939623

ABSTRACT

The native tick Amblyomma variegatum remains one of the most important tick species affecting cattle in West Africa. This hinders animal production by negatively impacting the health and reproduction of animals infested with the tick. Given the negative consequences on production quality and environmental health, the use of chemical products for tick control is increasingly being discouraged. Therefore, this study aimed to assess the acaricidal activity of essential oils such as Ageratum conyzoïdes, Cymbopogon citratus, Cymbopogon giganteus, Lippia multiflora and Ocimum gratissimum against specimens of A. variegatum from Burkina Faso. A larval immersion test was performed to investigate the larvicidal activities of these essential oils. Gas chromatography-mass spectrometry was used to determine the chemical compositions of essential oils. The chemical composition was predominantly oxygenated monoterpenes in A. conyzoïdes (48.71 %), C. citratus (99.9 %) and C. giganteus (73.63 %), while hydrocarbon monoterpenes were the most abundant in O. gratissimum (63.7 %) and hydrocarbon sesquiterpenes in L. multiflora (71.719 %). The recorded larvicidal activity, varied according to the species of plants and the dose applied. At a dose of 12.5 mg/mL, all essential oils studied, except L. multiflora (7.54 %), induced 100 % larval mortality. In this study, we highlight the promising larvicidal effects of local essential oils against A. variegatum. These essential oils can be used as bio-acaricides, which are effective and environmentally-friendly alternatives to chemical products. However, further investigations are required to determine the mechanisms of action of these essential oils for in vivo experimentation and their practical application in the control of A. variegatum ticks.


Subject(s)
Acaricides , Oils, Volatile , Rhipicephalus , Animals , Cattle , Oils, Volatile/chemistry , Plant Oils/pharmacology , Plant Oils/chemistry , Amblyomma , Burkina Faso , Monoterpenes/pharmacology , Acaricides/pharmacology
13.
bioRxiv ; 2023 Sep 11.
Article in English | MEDLINE | ID: mdl-37745554

ABSTRACT

The environmental challenges the human malaria parasite, Plasmodium falciparum, faces during its progression into its various lifecycle stages warrant the use of effective and highly regulated access to chromatin for transcriptional regulation. Microrchidia (MORC) proteins have been implicated in DNA compaction and gene silencing across plant and animal kingdoms. Accumulating evidence has shed light into the role MORC protein plays as a transcriptional switch in apicomplexan parasites. In this study, using CRISPR/Cas9 genome editing tool along with complementary molecular and genomics approaches, we demonstrate that PfMORC not only modulates chromatin structure and heterochromatin formation throughout the parasite erythrocytic cycle, but is also essential to the parasite survival. Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) experiments suggest that PfMORC binds to not only sub-telomeric regions and genes involved in antigenic variation but is also most likely a key modulator of stage transition. Protein knockdown experiments followed by chromatin conformation capture (Hi-C) studies indicate that downregulation of PfMORC induces the collapse of the parasite heterochromatin structure leading to its death. All together these findings confirm that PfMORC plays a crucial role in chromatin structure and gene regulation, validating this factor as a strong candidate for novel antimalarial strategies.

14.
Med. infant ; 30(2): 133-136, Junio 2023. ilus
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1443516

ABSTRACT

Los métodos diagnósticos clásicos de tuberculosis (TB) se basan en la utilización de baciloscopía y cultivo. La identificación del agente etiológico desde la positivización del cultivo requiere entre 10 y 15 días, mientras que el empleo de la reacción en cadena de la polimerasa (PCR) disminuye el tiempo a 24 h, lo que permite no solo identificar las subespecies del complejo Mycobacterium tuberculosis (CMTB) sino también diferenciarlas de otras especies ambientales clínicamente importantes (MOTT) facilitando el diagnóstico y tratamiento. El objetivo del presente trabajo fue determinar la utilidad de la PCR en la identificación temprana de las micobacterias pertenecientes al CMTB, a partir de cultivos positivos, de pacientes con sospecha de TB, atendidos en un hospital pediátrico de alta complejidad, durante un período de cuatro años. A cada muestra, se le realizó baciloscopía y cultivo en medio líquido. A los cultivos positivos, una inmunocromatografía lateral (TBIDR) y luego PCR. El 4,6% del total de muestras (510/11.162) pertenecientes a 198 pacientes presentó cultivos positivos. Cuatrocientos veintiseis (84%) correspondieron a muestras respiratorias. El rendimiento de la baciloscopía directa fue del 41% (194/470). Cuatrocientos treinta y ocho (86%) resultaron M. tuberculosis, 21 (4%) Mycobacterium bovis, 7 (1%), M. bovis-BCG y 44 (9%) MOTT. La utilización de medios de cultivos líquidos junto con el empleo de PCR favorecen una rápida orientación microbiológica y constituye una estrategia útil para optimizar el manejo clínico de estas infecciones, desde el punto de vista terapéutico y epidemiológico, especialmente en pediatría (AU)


Classical diagnostic methods for tuberculosis (TB) are based on the use of smear microscopy and culture. The identification of the etiological agent from positive culture requires 10 to 15 days, while the use of the polymerase chain reaction (PCR) reduces the time to 24 h, which allows not only to identify the subspecies of the Mycobacterium tuberculosis complex (MTC) but also to differentiate them from clinically important environmental mycobacteria other than tuberculosis (MOTT), facilitating diagnosis and treatment. The aim of this study was to determine the usefulness of PCR in the early identification of mycobacteria belonging to the MTC, from positive cultures of patients with suspected TB seen in a pediatric tertiary hospital over a 4-year period. For each sample, smear microscopy and culture in liquid medium was performed. Positive cultures were subjected to lateral immunochromatography (TBIDR) and then PCR. Of the total number of samples (510/11,162) belonging to 198 patients, 4.6% showed positive cultures; 426 (84%) were respiratory samples. The direct smear microscopy yield was 41% (194/470). Overall, 438 (86%) were found to be M. tuberculosis, 21 (4%) Mycobacterium bovis, 7 (1%), M. bovis-BCG, and 44 (9%) MOTT. The use of liquid culture media together with the use of PCR favors a rapid microbiological orientation and is a useful strategy to optimize the clinical management of these infections, from a therapeutic and epidemiological point of view, especially in children (AU)


Subject(s)
Humans , Infant , Child, Preschool , Child , Adolescent , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Polymerase Chain Reaction/instrumentation , Mycobacterium tuberculosis/isolation & purification , Mycobacterium tuberculosis/classification , Retrospective Studies
15.
Int Ophthalmol ; 43(9): 3321-3328, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37217809

ABSTRACT

PURPOSE: We developed model eyes using six polymer materials to determine which materials were most appropriate in simulating real human sclera and extraocular muscle (EOM). METHODS: Five three-dimensional (3-D) printed polymers (FlexFill, PolyFlex, PCTPE, Soft PLA, and NinjaFlex) and one silicone material were systematically tested by board-certified ophthalmologists and senior ophthalmology residents. Material testing included scleral passes with 6-0 Vicryl sutures through each eye model. Participants completed a survey designed to collect demographic data, subjective assessment of each material's accuracy in simulating real human sclera and EOM, and a ranking for each polymer material to identify which would be most suitable for an ophthalmic surgery training tool. The Wilcoxon signed-rank test was conducted to determine if there was a statistically significant difference in the distribution of ranks between the polymer materials. RESULTS: The distribution of ranks for silicone material's "sclera" and "EOM" components were statistically significantly higher than that of all other polymer materials (all p < 0.05). Silicone material received the highest rank for both "sclera" and "EOM" components. Survey results indicated that the silicone material effectively simulated real human tissue. CONCLUSION: Silicone model eyes performed better than 3-D printed polymers as an educational tool for incorporation into a microsurgical training curriculum. Silicone models provide a low-cost teaching tool that allows for independent practice of microsurgical techniques without requiring a wet-laboratory facility.


Subject(s)
Internship and Residency , Ophthalmology , Humans , Polymers , Clinical Competence , Ophthalmology/education , Silicones
16.
Ticks Tick Borne Dis ; 14(2): 102117, 2023 03.
Article in English | MEDLINE | ID: mdl-36603230

ABSTRACT

Heartwater, or cowdriosis, is a virulent tick-borne rickettsial disease of ruminants caused by Ehrlichia ruminantium, biologically transmitted by Amblyomma species (A. variegatum in West Africa). In West Africa, this bacterium was recently reported to naturally infect the invasive cattle tick, Rhipicephalus microplus (Rm) through trans-ovarian transmission from replete adult females to offspring. A 'sheep-tick-sheep' cycle was set up to determine whether feeding the progeny of these ticks on naïve sheep could lead to infection, and to compare clinical outcomes resulting from this transmission with those observed following infection by the natural A. variegatum (Av) vector. Using local strains of ticks (KIMINI-Rm and KIMINI-Av) and of E. ruminantium (BK242), we recorded, using the PCR technique, the presence of bacterial DNA in ticks (larvae for Av and females for Rm) engorged on sheep inoculated by BK242-infected blood. The bacterial DNA was also detected in the next stages of the lifecycle of R. microplus (eggs and larvae), and in sheep infested either by those R. microplus larvae or by A. variegatum nymphs moulted from larvae engorged on blood-inoculated sheep. Bacterial infection in these sheep was demonstrated by detecting antibodies to E. ruminantium using the MAP1-B ELISA and by isolation of the bacterium on cell culture from blood. The sequences of PCS20 gene detected in ticks and sheep were identical to that of the BK242 strain. Our results confirm that R. microplus can acquire and transmit E. ruminantium to the next stage. However, this transmission resulted in a mild subclinical disease whereas severe clinical disease was observed in sheep infested by A. variegatum infected nymphs, suggesting differences in the tick/bacteria relationship. Future studies will focus on replicating these findings with ticks of different isolates and life stages to determine if R. microplus is playing a role in the epidemiology of heartwater in West Africa. Additionally, studies will investigate whether sheep that are seropositive due to infestation by E. ruminantium-infected R. microplus are subsequently protected against heartwater. Such data will add to our understanding of the possible impact of R. microplus in areas where it has become recently established.


Subject(s)
Ehrlichia ruminantium , Heartwater Disease , Rhipicephalus , Female , Sheep , Animals , Ehrlichia ruminantium/genetics , Rhipicephalus/genetics , DNA, Bacterial , Heartwater Disease/epidemiology , Heartwater Disease/microbiology , Africa, Western/epidemiology
17.
Vet Med Sci ; 9(1): 345-352, 2023 01.
Article in English | MEDLINE | ID: mdl-36508582

ABSTRACT

BACKGROUND: Ticks are obligate hematophagous arthropods capable of transmitting a great variety of endemic and emerging pathogens causing diseases in animals and humans. OBJECTIVES: The aim of this study was to investigate the presence of Bartonella spp., Rickettsia spp., Borrelia burgdorferi sensu lato (s.l.) and Anaplasma phagocytophilum in ticks collected from cattle in Benin and Togo. METHODS: Overall, 396 (148 males, 205 females and 43 nymphs) ticks were collected from cattle in 17 districts (Benin and Togo) between 2019 and 2020. Ticks were pooled into groups of 2-6 ticks per pool according to individual host, location, species and developmental stage. The DNA of each pool was extracted for molecular screening. RESULTS: PCR results revealed that 20 tick pools were positive for Bartonella spp. (Benin and Togo) and 23 tick pools positive for Rickettsia spp. (Benin), while all pools were negative for A. phagocytophilum and B. burgdorferi s.l. Sequence analysis of positive Rickettsia samples revealed the presence of Rickettsia aeschlimannii. CONCLUSIONS: The present study highlights the presence of zoonotic agents in ticks collected from cattle in Benin and Togo. This information will raise awareness of tick-borne diseases among physicians and veterinarians, stimulate further studies to monitor these pathogens, and advise on necessary measures to control the spread of these zoonoses.


Subject(s)
Cattle Diseases , Ixodes , Tick Infestations , Male , Female , Animals , Cattle , Humans , Ixodes/microbiology , Benin/epidemiology , Togo/epidemiology , Tick Infestations/epidemiology , Tick Infestations/veterinary , Zoonoses/epidemiology , Cattle Diseases/epidemiology , Cattle Diseases/microbiology
18.
Med. infant ; 29(4): 268-274, dic 2022. ilus, tab
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1415399

ABSTRACT

Las infecciones por Chlamydia trachomatis han aumentado su prevalencia, especialmente en jóvenes embarazadas. Esto adquiere relevancia en pediatría por el elevado riesgo de transmisión vertical al neonato y su potencial gravedad en el lactante. Estas infecciones requieren de un alto índice de sospecha, por cuadro clínico atípico y signos radiológicos inespecíficos. Los métodos diagnósticos convencionales presentan limitaciones para su detección. Las técnicas moleculares son las recomendadas por su elevada sensibilidad, especificidad y rapidez, lo cual permite una terapéutica adecuada y oportuna. En este estudio, desarrollado en una unidad de cuidados intensivos neonatales de un hospital de alta complejidad durante 12 años, se describieron las características de la población, su presentación clínica y evolución. La detección microbiológica se realizó por métodos moleculares. Se incluyeron 29 pacientes (p) con infección por C. trachomatis (3,9% del total de muestras enviadas),13 p con infección respiratoria y 16 p con compromiso ocular. La mediana de edad fue de 19 días al momento del diagnóstico y el 65% de las gestantes tenía <25 años. Veinticuatro p (83%) eran recién nacidos a término y 23 p (79%) previamente sanos. Nueve p (31%) presentaron fiebre al momento del ingreso y 12 (41%) eosinofilia. De los 13 p con enfermedad respiratoria, 9 (69%) consultaron por tos y 11 (85%) con hipoxemia, con requerimientos de oxígeno en 8 (61%), asistencia respiratoria mecánica en 3 (23%) y uno (16%) requirió ECMO. Los hallazgos radiológicos mostraron un patrón intersticial inespecífico. Nueve p (31%) presentaron coinfección y uno falleció asociado a influenza A (AU)


The prevalence of Chlamydia trachomatis infections has increased, especially among young pregnant women. This is of particular relevance in pediatrics due to the high risk of motherto-child transmission and the potential severity of the infection in infants. A high index of suspicion is required for these infections due to the atypical clinical features and non-specific radiological signs. The usefulness of conventional diagnostic methods is limited. Molecular techniques are recommended because of their high sensitivity, specificity, and speed, allowing for adequate and timely treatment. In this 12-year study conducted in a neonatal intensive care unit of a tertiary-care hospital, patient characteristics, clinical presentation, and outcome are described. Microbiological detection was performed using molecular methods. Twenty-nine patients with C. trachomatis infection (3.9% of the total samples submitted), of whom 13 had respiratory tract infection and 16 ocular involvement, were included. The median age at diagnosis was 19 days and 65% of the mothers were <25 years old. Twenty-four p (83%) were term newborns and 23 patients (79%) were previously healthy. On admission, 9 patients (31%) had fever and 12 (41%) had eosinophilia. Of the 13 patients with respiratory tract involvement, 9 (69%) consulted for cough and 11 (85%) had hypoxemia, requiring oxygen in 8 (61%), mechanical ventilation in 3 (23%), and ECMO in 1 (16%). Radiological findings showed a nonspecific interstitial pattern. Nine patients (31%) presented with coinfection, one of whom died due to an associated influenza A infection (AU)


Subject(s)
Humans , Pregnancy , Infant, Newborn , Chlamydia Infections/complications , Chlamydia Infections/diagnosis , Chlamydia Infections/therapy , Intensive Care Units, Neonatal , Sexually Transmitted Diseases/etiology , Sexually Transmitted Diseases/epidemiology , Polymerase Chain Reaction/methods , Infectious Disease Transmission, Vertical , Chlamydia trachomatis/isolation & purification , Retrospective Studies , Anti-Bacterial Agents/therapeutic use
19.
Int J Surg ; 104: 106813, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35948185

ABSTRACT

BACKGROUND: Time pressure can cause stress, subsequently influencing surgeons during minimally invasive procedures. This trial aimed to investigate the effect of time pressure on surgical quality, as assessed by force application and errors during minimally invasive surgical tasks. METHODS: Sixty-three participants (43 surgical novices trained to proficiency and 20 surgeons) performed four laparoscopic tasks (PEG transfer, precise Cutting, balloon resection, surgical knot) both with and without time pressure. The primary endpoint was the mean and maximal force exertion during each task. Secondary endpoints were the occurrence of predefined errors and the self-assessed stress level. RESULTS: Time pressure led to a significant shortening of the task time in all four tasks. However, significantly more errors were noticed under time pressure in one task (suture precision P < 0.001). Moreover, time pressure led to a significant increase in mean force in all tasks (PEG: P < 0.001; precision cutting: P = 0.001; surgical knot: P < 0.001; balloon: P = 0.004). In three tasks the maximal force application (PEG: P < 0.001; precision cutting: P < 0.001; surgical knot: P = 0.006) increased significantly. Performing the tasks under time pressure significantly increased the stress level. Cohort analysis revealed that time pressure impaired the performance of both, surgical novices and surgeons but novices were more strongly affected compared to surgeons. CONCLUSION: Time pressure during minimally invasive surgery may improve procedural time but impair the quality of surgical performance in terms of the incidence of errors and force exertion. Experience may only partially compensate for the negative influence of time pressure.


Subject(s)
Clinical Competence , Laparoscopy , Cross-Over Studies , Humans , Minimally Invasive Surgical Procedures , Prospective Studies , Task Performance and Analysis
20.
Sci Rep ; 12(1): 14584, 2022 Aug 26.
Article in English | MEDLINE | ID: mdl-36028742

ABSTRACT

Finding suitable p-type dopants, as well as reliable doping and characterization methods for the emerging wide bandgap semiconductor [Formula: see text]-[Formula: see text] could strongly influence and contribute to the development of the next generation of power electronics. In this work, we combine easily accessible ion implantation, diffusion and nuclear transmutation methods to properly incorporate the Cd dopant into the [Formula: see text]-[Formula: see text] lattice, being subsequently characterized at the atomic scale with the Perturbed Angular Correlation (PAC) technique and Density Functional Theory (DFT) simulations. The acceptor character of Cd in [Formula: see text]-[Formula: see text] is demonstrated, with Cd sitting in the octahedral Ga site having a negative charge state, showing no evidence of polaron deformations nor extra point defects nearby. The possibility to determine the charge state of Cd will allow assessing the doping type, in particular proving p-type character, without the need for ohmic contacts. Furthermore, a possible approach for contactless charge mobility studies is demonstrated, revealing thermally activated free electrons for temperatures above [Formula: see text] 648 K with an activation energy of 0.54(1) and local electron transport dominated by a tunneling process between defect levels and the Cd probes at lower temperatures.

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