Gongylonema sp. in the Tongue of a Brown-Nosed Coati (Nasua nasua) from the Brazilian Atlantic Forest.

Two parasites were collected from the epithelial layer of the tongue mucosa of a brown-nosed coati (Nasua nasua) in an area of Atlantic Forest in Minas Gerais State, Brazil. These were identified as female Gongylonema sp. nematodes, not previously reported in Brazilian wild carnivores.

Walking with shorter stride length could improve knee kinetics of patients with medial knee osteoarthritis.

Walking with a shorter stride length (SL) was recently proposed for gait retraining in medial knee osteoarthritis; however it was never assessed in this patient population. This study tested the hypothesis that shortening SL while maintaining walking speed reduces knee adduction (KAM) and flexion (KFM) moments in patients with medial knee osteoarthritis. Walking trials with normal SL and SL reduced by 0.10 m and 0.15 m were recorded for 15 patients (10 men, 55.5 ± 8.7 years old, 24.6 ± 3.0 kg/m2). SL was modified using an augmented reality system displaying target footprints on the floor. Repeated one-way ANOVAs and post-hoc paired t-tests were performed to compare gait measures between normal and reduced SL. The individual effects of SL reduction were analyzed using descriptive statistics. Group analysis indicated significant decreases in KAM impulse with both SL reductions (p < 0.05). No systematic change was observed in the first peaks KAM and KFM when walking with reduced SL (p > 0.05). Individually, 33 % of the patients decreased the peak KAM, whereas 20 % decreased the KAM impulse. Among these patients with a decrease in peak KAM or in KAM impulse, 0 % and 33 % had a simultaneous increase in peak KFM, respectively. In conclusion, this study showed that SL shortening can decrease kinetic measures associated with the progression of medial knee osteoarthritis in some patients, demonstrating the importance of considering SL modifications on an individual basis. While further research is necessary, notably regarding dose-response relationships and long-term effects, these findings are particularly encouraging because SL reductions could be easily integrated into rehabilitation protocols.

Ten-year follow-up of a total knee prosthesis combining multi-radius, ultra-congruency, posterior-stabilization and mobile-bearing insert shows long-lasting clinically relevant improvements in pain, stiffness, function and stability.

PURPOSE: There is a paucity of data available on total knee prostheses combining dual-radius, ultra-congruency, posterior-stabilization and mobile-bearing insert. This prospective cohort study aimed to assess the clinical evolution of the FIRST® prosthesis (Symbios Orthopédie, Yverdon, CH), the earliest prosthesis with this particular design. It was hypothesized that the primary outcomes, evaluating pain, stiffness, function and stability, would improve following arthroplasty and remain improved during the follow-up period of 10 years. METHODS: All patients programmed for a total knee arthroplasty using a FIRST® prosthesis at our university hospital between 2006 and 2008 were invited to participate. Study knees were evaluated pre-operatively as well as one, five and ten years post-operatively. Patients filled out questionnaires at each evaluation point and had a radiographic assessment at the five-year and ten-year follow-ups. Primary outcomes were the total, pain, stiffness and function measures of the Western Ontario and McMaster Universities Osteoarthritis questionnaire (WOMAC) and the knee and function measures of the Knee Society Score (KSS). Friedman and Wilcoxon's rank-sum tests were used to compare measures across time points. RESULTS: Hundred and twenty four prostheses were included (baseline demographics: 69.9 ± 8.3 years old, 28.1 ± 4.3 kg/m2, 54% male) and 68 could be followed during ten years. Five prostheses underwent a revision. All other prostheses lost at follow-up were lost for reasons unrelated to the prosthesis. All primary measures reported statistically and clinically significant improvements between baseline and the three follow-up evaluations. Statistically significant improvements at the three follow-up evaluations were also observed for most secondary measures. There was no implant loosening. At ten-year follow-up, radiolucent lines were observed in 2.9% femoral implants and 1.5% tibial implants. CONCLUSION: The positive results observed in all domains of assessment and the small revision rate demonstrated an effective functioning of the FIRST® prosthesis during the ten-year follow-up period. The results, globally similar to those previously published for other prosthesis designs, encourage the development of assistive methods to select the most appropriate designs on an individual basis. LEVEL OF EVIDENCE: IV, prospective cohort study.

Two-level modeling approach to identify the regulatory dynamics capturing drug response heterogeneity in single-cells.

Single-cell multimodal technologies reveal the scales of cellular heterogeneity impairing cancer treatment, yet cell response dynamics remain largely underused to decipher the mechanisms of drug resistance they take part in. As the phenotypic heterogeneity of a clonal cell population informs on the capacity of each single-cell to recapitulate the whole range of observed behaviors, we developed a modeling approach utilizing single-cell response data to identify regulatory reactions driving population heterogeneity in drug response. Dynamic data of hundreds of HeLa cells treated with TNF-related apoptosis-inducing ligand (TRAIL) were used to characterize the fate-determining kinetic parameters of an apoptosis receptor reaction model. Selected reactions sets were augmented to incorporate a mechanism that leads to the separation of the opposing response phenotypes. Using a positive feedback loop motif to identify the reaction set, we show that caspase-8 is able to encapsulate high levels of heterogeneity by introducing a response delay and amplifying the initial differences arising from natural protein expression variability. Our approach enables the identification of fate-determining reactions that drive the population response heterogeneity, providing regulatory targets to curb the cell dynamics of drug resistance.

Association between changes in the knee adduction moment and changes in knee pain and function in response to non-surgical biomechanical interventions for medial knee osteoarthritis: a systematic review.

INTRODUCTION: There is lack of understanding of the relationship between knee adduction moment (KAM) reductions and improvements in pain or function in patients with knee osteoarthritis (KOA). Moreover, there is no systematic review describing the longitudinal relationship between KAM changes and subsequent changes in pain and/or physical function. WE AIMED TO: 1) investigate the relationship between changes in KAM induced by non-surgical biomechanical interventions and consecutive changes in pain and/or physical function in patients with medial KOA and; 2) compare this relationship for different interventions. EVIDENCE ACQUISITION: We considered eligible all RCTs using biomechanical interventions aimed to reduce KAM in KOA patients, that measured pain/function. We used Cohen's d effect size to quantify outcome measurements. EVIDENCE SYNTHESIS: Fourteen papers reporting 11 studies were identified. Braces were tested in 6 studies, insoles in 5 studies, shoes in 3 studies and gait retraining in 2 studies. Methodological differences were large among studies. Large effect sizes (≥0.8) changes in pain/function were observed with interventions having at least a small KAM effect size (≥0.2), suggesting an association between KAM and pain/function changes. A linear trend was observed between inter-intervention KAM and VAS pain effect sizes, based on 4 studies. No firm conclusions could be drawn for the different intervention types. CONCLUSIONS: There was a trend toward larger KAM reductions leading to larger improvements in pain/function in non-surgical biomechanical interventions. Additional high-quality RCT with consistent methodology are needed to fully characterize the association between KAM and pain/function changes.

Profiling the Non-genetic Origins of Cancer Drug Resistance with a Single-Cell Functional Genomics Approach Using Predictive Cell Dynamics.

Non-genetic heterogeneity observed in clonal cell populations is an immediate cause of drug resistance that remains challenging to profile because of its transient nature. Here, we coupled three single-cell technologies to link the predicted drug response of a cell to its own genome-wide transcriptomic profile. As a proof of principle, we analyzed the response to tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) in HeLa cells to demonstrate that cell dynamics can discriminate the transient transcriptional states at the origin of cell decisions such as sensitivity and resistance. Our same-cell approach, named fate-seq, can reveal the molecular factors regulating the efficacy of a drug in clonal cells, providing therapeutic targets of non-genetic drug resistance otherwise confounded in gene expression noise. A record of this paper's transparent peer review process is included in the Supplemental Information.

Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test

Objective: Cannabidiol (CBD), one of the non-psychotomimetic compounds of Cannabis sativa, causes anxiolytic-like effects in animals, with typical bell-shaped dose-response curves. No study, however, has investigated whether increasing doses of this drug would also cause similar curves in humans. The objective of this study was to compare the acute effects of different doses of CBD and placebo in healthy volunteers performing a simulated public speaking test (SPST), a well-tested anxiety-inducing method. Method: A total of 57 healthy male subjects were allocated to receive oral CBD at doses of 150 mg (n=15), 300 mg (n=15), 600 mg (n=12) or placebo (n=15) in a double-blind procedure. During the SPST, subjective ratings on the Visual Analogue Mood Scale (VAMS) and physiological measures (systolic and diastolic blood pressure, heart rate) were obtained at six different time points. Results: Compared to placebo, pretreatment with 300 mg of CBD significantly reduced anxiety during the speech. No significant differences in VAMS scores were observed between groups receiving CBD 150 mg, 600 mg and placebo. Conclusion: Our findings confirm the anxiolytic-like properties of CBD and are consonant with results of animal studies describing bell-shaped dose-response curves. Optimal therapeutic doses of CBD should be rigorously determined so that research findings can be adequately translated into clinical practice.

Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test.

OBJECTIVE: Cannabidiol (CBD), one of the non-psychotomimetic compounds of Cannabis sativa, causes anxiolytic-like effects in animals, with typical bell-shaped dose-response curves. No study, however, has investigated whether increasing doses of this drug would also cause similar curves in humans. The objective of this study was to compare the acute effects of different doses of CBD and placebo in healthy volunteers performing a simulated public speaking test (SPST), a well-tested anxiety-inducing method. METHOD: A total of 57 healthy male subjects were allocated to receive oral CBD at doses of 150 mg (n=15), 300 mg (n=15), 600 mg (n=12) or placebo (n=15) in a double-blind procedure. During the SPST, subjective ratings on the Visual Analogue Mood Scale (VAMS) and physiological measures (systolic and diastolic blood pressure, heart rate) were obtained at six different time points. RESULTS: Compared to placebo, pretreatment with 300 mg of CBD significantly reduced anxiety during the speech. No significant differences in VAMS scores were observed between groups receiving CBD 150 mg, 600 mg and placebo. CONCLUSION: Our findings confirm the anxiolytic-like properties of CBD and are consonant with results of animal studies describing bell-shaped dose-response curves. Optimal therapeutic doses of CBD should be rigorously determined so that research findings can be adequately translated into clinical practice.

Oslerus (Anafilaroides) sp. in a Jaguarundi (Puma yagouaroundi) from Brazil.

We report the occurrence of Oslerus (Anafilaroides) sp. parasitizing the lung of the jaguarundi (Puma yagouaroundi) in Brazil.

A new metastrongyloidean species (Nematoda) parasitizing pulmonary arteries of Puma (Herpailurus) yagouaroundi (É. Geoffroy, 1803) (Carnivora: Felidae) from Brazil.

Angiostrongylus felineus n. sp. (Nematoda, Metastrongyloidea), parasitic in Puma (Herpailurus) yagouaroundi (É. Geoffroy, 1803) (Carnivora, Felidae) from the municipality of Juiz de Fora, Minas Gerais state, Brazil, is described and illustrated herein. Angiostrongylus felineus n. sp. differs from all congeneric species by having the anterior extremity with accentuated cuticular expansion and by smaller size of spicules. This study describes for the first time a species of Angiostrongylus in a wild Felidae in Brazil.

Crenosoma brasiliense sp. n. (Nematoda: Metastrongyloidea) parasitic in lesser grison, Galictis cuja (Molina, 1782) (Carnivora, Mustelidae) from Brazil, with a key to species of Crenosoma Molin, 1861.

This study describes Crenosoma brasiliense (Nematoda, Metastrongyloidea), a new species parasitic in bronchi and bronchioles of Galictis cuja (Molina) (Carnivora, Mustelidae) from Brazil. This species differs from other 11 species of Crenosoma by having a cuticular projection at the distal end of the spicules, forming a prominent blade at the tip of the spicule, a vulval cuticular appendage with a triangular shape and prominent vulval lips. There are no previous records of species of Metastrongyloidea in G. cuja or species of Crenosoma in South America. Therefore, the new species represents the first host record and first geographical record of species of Crenosoma in South America.

Dipylidium caninum (Cyclophyllidea, Dipylidiidae) in a wild carnivore from Brazil.

We report Dipylidium caninum for the first time in a wild carnivore in Brazil, the crab-eating fox (Cerdocyon thous). Presence of the cestode could be the consequence of anthropogenic expansion into natural habitats of this host, as this parasite has only previously been reported in domestic hosts in Brazil.

Prevalence and pathology of the nematode Heterakis gallinarum, the trematode Paratanaisia bragai, and the protozoan Histomonas meleagridis in the turkey, Meleagris gallopavo.

The prevalence of infection and associated pathology induced by two helminth and one protozoan species infecting Brazilian turkeys are reported. The intestinal nematode Heterakis gallinarum appeared with a prevalence of 70% in the infected birds, without gross lesions when not associated to the protozoan Histomonas meleagridis. Histological findings in the ceca were represented by the presence of H. gallinarum worms, intense chronic diffuse inflammatory processes with mononuclear and polymorphonuclear (heterophils) leucocyte infiltrations. The prevalence of the protozoan H. meleagridis associated to H. gallinarum was of 2.5% and microscopic examination revealed a severe inflammatory process in the liver and cecum with the presence of small clear areas with round eosinophilic parasites. Gross lesions were absent in turkeys infected with the renal digenetic trematode Paratanaisia bragai; the parasite was prevalent in 20% of the cases and cross-sections of the kidneys showed a remarkable distension of the collecting ducts with several worms in the lumen. The walls of the ducts presented a discrete heterophilic infiltrate among mononuclear cells.

Prevalence and pathology of the nematode Heterakis gallinarum, the trematode Paratanaisia bragai, and the protozoan Histomonas meleagridis in the turkey, Meleagris gallopavo

The prevalence of infection and associated pathology induced by two helminth and one protozoan species infecting Brazilian turkeys are reported. The intestinal nematode Heterakis gallinarum appeared with a prevalence of 70 percent in the infected birds, without gross lesions when not associated to the protozoan Histomonas meleagridis. Histological findings in the ceca were represented by the presence of H. gallinarum worms, intense chronic diffuse inflammatory processes with mononuclear and polymorphonuclear (heterophils) leucocyte infiltrations. The prevalence of the protozoan H. meleagridis associated to H. gallinarum was of 2.5 percent and microscopic examination revealed a severe inflammatory process in the liver and cecum with the presence of small clear areas with round eosinophilic parasites. Gross lesions were absent in turkeys infected with the renal digenetic trematode Paratanaisia bragai; the parasite was prevalent in 20 percent of the cases and cross-sections of the kidneys showed a remarkable distension of the collecting ducts with several worms in the lumen. The walls of the ducts presented a discrete heterophilic infiltrate among mononuclear cells.

Taxonomic status of Ascocotyle (Phagicola) rara Arruda, Muniz-Pereira et Pinto, 2002 (Digenea: Heterophyidae).

Holotype and paratype of Ascocotyle (Phagicola) rara Arruda, Muniz-Pereira et Pinto, 2002, a heterophyid trematode recently described on the basis of two worms collected by Lauro Travassos in 1921 in the intestine of Ixobrychus exilis (Gmelin) from Brazil, were studied. The morphology of the worms revealed their conspecificity with Ascocotyle (Phagicola) angeloi Travassos, 1928 found in the same host. Both the taxa have a similar length (between 600 and 900 microm) and shape of the body (long pyriform), the long intestinal caeca reaching to the ovarian level, a long posterior muscular prolongation of the oral sucker and the prepharynx, transverse uterine loops situated between the ventral sucker and testes, and the gonotyl with more than 20 digitiform pockets. Consequently, A. (P.) rara is proposed as a junior synonym of Ascocotyle (Phagicola) angeloi.

[Natural helminth infection in Sicalis flaveola (Linnaeus, 1766), by Acuaria mayori Lent, Freitas and Proença, 1945 (Nematoda: Acuarioidea) in Brazil]. / Infecção natural em Sicalis flaveola (Linaeus, 1766) por Acuaria mayori lent, freitas e proença, 1945 (nematoda: acuarioidea) no Brasil.

This is the first report of a natural infection in the saffron finch Sicalis flaveola (Linnaeus, 1766) captured in Brazil, with the establishment of a new host record for the acuarioid nematode Acuaria mayori Lent, Freitas and Proença, 1945, previously referred in Cyanocorax chrysops (Vieillot, 1818) from Paraguay and Sporophila caerulescens caerulescens (Vieillot, 1823) and C. cyanomelas (Wied, 1821) from Brazil and Myarchus nuttingi (Ridgway, 1883) from Costa Rica.

Oswaldotrema nacinovici gen. nov. sp. nov. (Digenea: Philophthalmidae) from Numenius phaeopus (Aves: Scolopacidae) in Brazil

A new genus, Oswaldotrema gen. nov. is proposed. Oswaldotrema nacinovici sp. nov. is descibed from Numenius phaeopus Latham, 1790. Differentiation from the other related genera, namely Philophthalmus, Pygorchis, Proctobium, Parorchis, Echinostephila, Cloacitrema, Pittacium, Ophthalmotrema, Skrjabinovermis and Paratrema, was based on morphological characters, mainly on those referring to the body surface, body shape, head, esophagus, pharynx, acetabulum, vitellaria, vitelline reservoir and seminal vesicle.

On two nematodes from Brazilian birds and description of a new species (Acuarioidea, Schistorophinae) parasitizing Laterallus viridis (Müller, 1776) (Gruiformes, Rallidae)

The present paper reports acuarioid nematodes recovered from avian hosts. A new species of the genus Schistorophus Railliet, 1916 is proposed based mainly on findings referring to ptilina, spicules and vagina. Ancyracanthopsis coronata (Molin, 1860) Chabaud & Petter, 1959 is referred again in Brazil since its proposition in 1860, from specimens recovered from a Brazilian bird. A revised key to the species of the genus Schistorophus is also presented