Accessory subscapularis muscle - A forgotten variation?

The quadrangular space is a space in the axilla bounded by the inferior margin of the teres minor muscle, the superior margin of the teres major muscle, the lateral margin of the long head of the triceps brachii muscle and the surgical neck of the humerus, medially. The axillary nerve (C5-C6) and the posterior circumflex humeral artery and veins pass through this space in order to supply their territories. The subscapularis muscle is situated into the scapular fossa and inserts itself into the lesser tubercle of the humerus, thus helping stabilize the shoulder joint. A supernumerary muscle known as accessory subscapularis muscle originates from the anterior surface of the muscle and usually inserts itself into the shoulder joint. It is a rare variation with few reports of its existence and incidence. We present a case of the accessory subscapularis muscle in a male cadaver fixated with a 10% formalin solution. The muscle passed anteriorly to the axillary nerve, thus, predisposing an individual to quadrangular space compression syndrome. We perform a review of the literature and address its clinical, anthropological and anatomical significance.

The REWRITE Study - REal-WoRld effectIveness of TrifluridinE/tipiracil in Patients with Previously Treated Metastatic Colorectal Cancer.

AIMS: In the pivotal RECOURSE trial, trifluridine/tipiracil improved survival outcomes in refractory metastatic colorectal cancer (mCRC), while demonstrating an acceptable toxicity profile. Routine clinical practice evidence is important to support the ongoing value of recently approved medicines. Our objective was to assess the utilisation patterns and real-world effectiveness of trifluridine/tipiracil in previously treated mCRC patients. MATERIALS AND METHODS: This was a retrospective observational study including consecutive patients who started trifluridine/tipiracil between 1 April 2018 and 30 September 2019 in the medical oncology departments of three major public hospitals in Portugal. The primary outcome measure was overall survival. Associations between overall survival and patient and tumour characteristics were assessed using multivariate Cox regression analyses. RESULTS: In total, 111 patients were included in the study, with a mean age of 64 years. From these, 45.9% received two prior lines of treatment, 47.8% had three or more previous lines of treatment and 83.6% had Eastern Cooperative Oncology Group (ECOG) performance status 0-1 at baseline. The median duration of trifluridine/tipiracil treatment was 3.7 cycles (95% confidence interval 3.4-4.1). Most patients (80.4%) remained on their planned dose throughout the trifluridine/tipiracil treatment period, fulfilling 100% relative dose intensity. The median overall survival in the total study cohort was 7.9 months (95% confidence interval 6.4-9.8) and the median progression-free survival was 3.4 months (95% confidence interval 3.2-3.9). The median overall survival was significantly higher in patients with a normal serum lactate dehydrogenase (LDH) level (median overall survival 11.2 months for [135, 205] IU/l LDH [95% confidence interval 8.2-NR] and 13.6 months for [205, 251] IU/l LDH [95% confidence interval 8.2-NR]) and in better fitted (ECOG = 0-1) patients (median overall survival 8.0 months; 95% confidence interval 6.7-10.0). The median time to worsening performance status was 6.2 months (95% confidence interval 5.0-8.0). Treatment discontinuation due to adverse events was low (3.1%). CONCLUSION: Our study confirms the effectiveness of trifluridine/tipiracil in real-life mCRC patients. Overall survival and progression-free survival outcomes are consistent with the efficacy profile reported in the earlier randomised RECOURSE clinical trial. Like other real-world studies, we found no additional safety concerns in the use of trifluridine/tipiracil.

The immunology of experimental Chagas' disease. 3. Rejection of allogeneic heart cells in vitro.

Experiments that consisted of incubation of Trypanosoma cruzi-sensitized lymphocytes derived from chronically infected rabbits and from rabbits repeatedly immunized with a small particle or membrane fraction derived from homogenates of T. cruzi forms, showed destruction of allogeneic, parasitized and nonparasitized heart cells in vitro. Mononuclear cells collected from peripheral blood were incubated for 1 h at 37 degrees C to isolate the lymphocytes. Following incubation, over 99% of the cells in the supernate were lymphocytes, which were utilized in these experiments. At the start of these experiments, 70-80% of the sensitized lymphocytes were unattached, small and round, with sparse filipodia. In the ensuing hours, marked heart cell destruction, similar to that seen in an active lesion when lymphocytes invade heart tissue, were observed. After 18 h incubation, about 65-70% of the lymphocytes were attached, larger, and rough surfaced. Inhibition of monocyte migration tests, each in the presence of the antigens of subcellular fractions of T. cruzi organisms and of allogeneic heart myofibers, indicated the presence of a cross-reacting antigen common to both the parasite and the heart in the small particle or membrane fractions. The particulate antigens of the 30,000 g, 35-min fraction of heart muscle gave rise to inhibition of monocyte migration as did the counterpart fraction derived from T. cruzi organisms. The destruction of nonparasitized target heart cells by T. cruzi-sensitized lymphocytes is an in vitro model of the chronic myocarditis of Chagas' disease, and the recognition of cross-reactive antigens of the host cell by T. cruzi-sensitized lymphocytes is believed to be the pathogenic basis for subsequent tissue injury in the chronic phase of this disease.

Alexithymia may explain the relationship between autistic traits and eating disorder psychopathology.

BACKGROUND: Autistic people are disproportionately vulnerable to anorexia nervosa and other eating disorders (ED), and within the general population, autistic traits correlate with ED psychopathology. A putative mechanism which may underpin this heightened risk is alexithymia, a difficulty identifying and describing emotional states which is observed in both autism and ED. In two experiments with independent non-clinical samples, we explored whether alexithymia might mediate the heightened risk of eating psychopathology in individuals high in autistic traits. METHODS: Our first experiment used the PROCESS macro for SPSS to examine relationships between alexithymia (measured by the Toronto Alexithymia Scale (TAS-20)), autistic traits (autism quotient (AQ)), and eating psychopathology (Eating Attitudes Test (EAT-26)) in 121 participants. Our second experiment (n = 300) replicated and furthered this analysis by examining moderating effects of sex and controlling for anxiety and depression as covariates. We also included an additional performance-based measure of alexithymia, the Levels of Emotional Awareness Scale (LEAS). RESULTS: Study 1 suggested that TAS-20 scores mediated the relationship between heightened autistic traits and eating psychopathology. Replication and further scrutiny of this finding, in study 2, revealed that this mediation effect was partial and specific to the female participants in this sample. The mediation effect appeared to be carried by the difficulty identifying feelings subscale of the TAS-20, even when depression and anxiety were controlled for. LEAS scores, however, were not significantly related to autistic traits or eating psychopathology. LIMITATIONS: Cross-sectional data prevents any conclusions around the direction and causality of relationships between alexithymia, autistic traits, and eating psychopathology (alongside depression and anxiety), necessitating longitudinal research. Our non-clinical sample was predominantly Caucasian undergraduate students, so it remains to be seen if these results would extrapolate to clinical and/or autistic samples. Divergence between the TAS-20 and LEAS raises crucial questions regarding the construct validity of these measures. CONCLUSIONS: Our findings with respect to autistic traits suggest that alexithymia could partially explain the prevalence of ED in autistic people and may as such be an important consideration in the pathogenesis and treatment of ED in autistic and non-autistic people alike. Further research with clinical samples is critical to explore these ideas. Differences between men and women, furthermore, emphasize the importance of looking for sex-specific as well as generic risk factors in autistic and non-autistic men and women.

Laparoscopic resection of left liver segments using the intrahepatic Glissonian approach.

BACKGROUND: Recent advances in laparoscopic techniques have resulted in growing indications for laparoscopic hepatectomy. However, this procedure has not been widely developed, and anatomic segmental liver resection is not currently performed due to difficulty controlling the segmental Glissonian pedicles laparoscopically. This study aimed to report a novel technique for laparoscopic anatomic resection of left liver segments using the intrahepatic Glissonian approach based on small incisions according to anatomic landmarks such as Arantius' and round ligaments. METHODS: Nine consecutive patients underwent laparoscopic liver resection using the intrahepatic Glissonian technique from April 2007 to June 2008. Five patients underwent laparoscopic bisegmentectomy 2-3, one laparoscopic left hemihepatectomy, two resections of segment 3, and one resection of segment 4. RESULTS: One patient required a blood transfusion. The mean operation time was 180 min (range, 120-300 min), and the median hospital stay was 3 days (range, 1-5 days). No patient had postoperative signs of liver failure or bile leakage. No postoperative mortality was observed. CONCLUSION: The main advantage of the intrahepatic Glissonian procedure over other techniques is the possibility of gaining a rapid and precise access to the left Glissonian sheaths facilitating left hemihepatectomy, bisegmentectomy 2-3, and individual resections of segments 2, 3, and 4. The authors believe that the intrahepatic Glissonian technique facilitates laparoscopic liver resection and may increase the development of segment-based laparoscopic liver resection.

Mining EEG scalp maps of independent components related to HCT tasks.

This work presents an unsupervised mining strategy, applied to an independent component analysis (ICA) of segments of data collected while participants are answering to the items of the Halstead Category Test (HCT). This new methodology was developed to achieve signal components at trial level and therefore to study signal dynamics which are not available within participants' ensemble average signals. The study will be focused on the signal component that can be elicited by the binary visual feedback which is part of the HCT protocol. The experimental study is conducted using a cohort of 58 participants.

Laparoscopic right hemihepatectomy for hepatolithiasis.

BACKGROUND: Liver resection is the definitive treatment for unilateral hepatolithiasis. Recently, laparoscopic major hepatectomias have become more common and are being performed in highly specialized centers. However, few laparoscopic liver resections for hepatolithiasis have been reported. Chen et al. reported two cases of laparoscopic left lobectomy for hepatolithiasis, but to our knowledge, right hepatectomy has never been reported to date. This video demonstrates technical aspects of a totally laparoscopic right hepatectomy in a patient with hepatolithiasis. METHODS: A 21-year-old woman with right-sided nonoriental primary intrahepatic stones was referred for surgical treatment. The operation followed four distinct phases: liver mobilization, dissection of the right portal vein and right hepatic artery, extrahepatic dissection of the right hepatic vein, and parenchymal transection with harmonic shears and linear staplers for division of segment 5 and 8 branches of the middle hepatic vein. No Pringles' maneuver was used. In contrast to liver resection for other indications, the right bile duct was enlarged and filled with stones. It was divided during parenchymal transection and left open. After removal of the surgical specimen, the biliary tree was flushed with saline until stone clearance, under radioscopic surveillance, was complete. The right hepatic duct then was closed with running suture. RESULTS: The operative time was 240 min, and the estimated blood loss was 120 ml, with no blood transfusion. The hospital stay was 5 days. At this writing, the patient is well and asymptomatic 7 months after the procedure. CONCLUSION: Laparoscopic liver resection is safe and feasible for patients with hepatolithiasis and should be considered for those suffering from intrahepatic stones. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00464-007-9666-1) contains supplementary material, which is available to authorized users.

Acquired cell-mediated immunodepression in acute Chagas' disease.

In this study two groups of patients with acute Chagas' disease were identified. Group one consisted of five patients with apparent acute Chagas' disease. These patients showed symptoms and signals of an acute illness, such as high fever and enlarged spleen. One of these patients developed severe myocarditis and heart failure. Group two consisted of seven patients with inapparent acute Chagas' disease. This was a nonclinical entity, not perceived by the patient who did not seek medical care. The diagnosis was made by the shift of a serologic test which indicates the presence of immunoglobulin M antibodies to Trypanosoma cruzi. The patients with apparent acute Chagas' disease showed positive delayed-type skin response to T. cruzi antigen. Also, their leukocytes showed significant inhibition of migration in the presence of this antigen. By contrast, the patients with the inapparent acute Chagas' disease did not show positive delayed-type skin response to T. cruzi antigen and no significant inhibition was observed when their cells migrated in the presence of this antigen. Of interest, none of these patients was capable of developing contact sensitivity to 2,4-dinitrochlorobenzene. However, three out of five patients with the apparent acute disease and all the normal control subjects showed positive contact reaction after sensitization to this drug. The results of these experiments would suggest that the thymus-derived (T)-lymphocyte function is depressed in patients with the clinically inapparent acute Chagas' disease. This immunodepression seems to be acquired in the course of the T. cruzi infection because all patients showed positive delayed-type skin response to at least one ubiquitous microbial extract, thus indicating previously normal T-cell function. We hypothesize that T. cruzi antigens may directly stimulate T cells with the concomitant release of factors that might become supressive for T-cell responses. Furthermore, the suppressive effect might interfere with the T-cell response to other antigens, such as to 2,4-dinitrochlorobenzene.

On the use of simulated annealing to automatically assign decorrelated components in second-order blind source separation.

In this paper, an automatic assignment tool, called BSS-AutoAssign, for artifact-related decorrelated components within a second-order blind source separation (BSS) is presented. The latter is based on the recently proposed algorithm dAMUSE, which provides an elegant solution to both the BSS and the denoising problem simultaneously. BSS-AutoAssign uses a local principal component analysis (PCA)to approximate the artifact signal and defines a suitable cost function which is optimized using simulated annealing. The algorithms dAMUSE plus BSS-AutoAssign are illustrated by applying them to the separation of water artifacts from two-dimensional nuclear overhauser enhancement (2-D NOESY) spectroscopy signals of proteins dissolved in water.

Chagas disease.

Chagas disease is the clinical condition triggered by infection with the protozoan Trypanosoma cruzi. The infection is transmitted by triatomine insects while blood feeding on a human host. Field studies predict that one third of an estimated 18 million T cruzi-infected humans in Latin America will die of Chagas disease. Acute infections are usually asymptomatic, but the ensuing chronic T cruzi infections have been associated with high ratios of morbidity and mortality: Chagas heart disease leads to unexpected death in 37.5% of patients, 58% develop heart failure and die and megacolon or megaoesophagus has been associated with death in 4.5%. The pathogenesis of Chagas disease appears to be related to a parasite-induced mutation of the vertebrate genome. Currently, treatment is unsatisfactory.

Automatic removal of high-amplitude artefacts from single-channel electroencephalograms.

In this work, we present a method to extract high-amplitude artefacts from single channel electroencephalogram (EEG) signals. The method is called local singular spectrum analysis (local SSA). It is based on a principal component analysis (PCA) applied to clusters of the multidimensional signals obtained after embedding the signals in their time-delayed coordinates. The decomposition of the multidimensional signals in each cluster is achieved by relating the largest eigenvalues with the large amplitude artefact component of the embedded signal. Then by reverting the clustering and embedding processes, the high-amplitude artefact can be extracted. Subtracting it from the original signal a corrected EEG signal results. The algorithm is applied to segments of real EEG recordings containing paroxysmal epileptiform activity contaminated by large EOG artefacts. We will show that the method can be applied also in parallel to correct all channels that present high-amplitude artefacts like ocular movement interferences or high-amplitude low frequency baseline drifts. The extracted artefacts as well as the corrected EEG will be presented.

ERP correlates of error processing during performance on the Halstead Category Test.

The Halstead Category Test (HCT) is a neuropsychological test that measures a person's ability to formulate and apply abstract principles. Performance must be adjusted based on feedback after each trial and errors are common until the underlying rules are discovered. Event-related potential (ERP) studies associated with the HCT are lacking. This paper demonstrates the use of a methodology inspired on Singular Spectrum Analysis (SSA) applied to EEG signals, to remove high amplitude ocular and movement artifacts during performance on the test. This filtering technique introduces no phase or latency distortions, with minimum loss of relevant EEG information. Importantly, the test was applied in its original clinical format, without introducing adaptations to ERP recordings. After signal treatment, the feedback-related negativity (FRN) wave, which is related to error-processing, was identified. This component peaked around 250ms, after feedback, in fronto-central electrodes. As expected, errors elicited more negative amplitudes than correct responses. Results are discussed in terms of the increased clinical potential that coupling ERP information with behavioral performance data can bring to the specificity of the HCT in diagnosing different types of impairment in frontal brain function.

Characterisation of a Trypanosoma cruzi acidic 30 kDa cysteine protease.

A novel proteolytic activity was identified in epimastigote, amastigote and trypomastigote forms of Trypanosoma cruzi using the fluorogenic substrate N-Succinyl-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin. Epimastigotes showed enzyme activity to be 2-fold higher than amastigotes and trypomastigotes. The protease that displays this activity was purified from epimastigote forms by a four step chromatographic procedure: Diethylaminoethyl-Sephacel, Phenyl-Sepharose, Phenyl-Superose, and Concanavalin A Sepharose columns. The purified enzyme is a glycoprotein that migrates as a 30 kDa protein in 12.5% SDS-polyacrylamide gel electrophoresis (PAGE), under reducing conditions. Its optimal enzymatic activity on both fluorogenic and protein substrates was found to occur at an acidic pH. The inhibition pattern of the purified 30 kDa protease showed that it belongs to the cysteine-protease class. In addition to the synthetic substrate, the purified protease hydrolysed bovine serum albumin (BSA) and human type I collagen. The N-terminal amino acid sequence of the protease shows similarity to the mammalian cathepsin B protease.

Involvement of calyculin A-sensitive phosphatase(s) in the differentiation of Trypanosoma cruzi trypomastigotes to amastigotes.

Differentiation of the non-dividing trypomastigote form of Trypanosoma cruzi, the causative agent of Chagas disease, to the dividing amastigote form normally occurs in cytoplasm of infected cells. Here we show that calyculin A. a potent inhibitor of protein phosphatases 1 and 2A, induces at pH 7.5 extracellular transformation of long slender trypomastigotes to round amastigote-like forms which acquire characteristic features observed after the normal differentiation process: repositioning and structural changes of the kinetoplast, release of surface neuraminidase, and expression of amastigote-specific epitopes. Calyculin A inhibits parasite phosphatases and changes in the phosphorylation of specific proteins occur during the transformation process. As an exposure of trypomastigotes to calyculin A concentrations as low as 1 nM and for only 1-2 h is sufficient to induce transformation, the inhibition of calyculin A-sensitive phosphatase(s) appears to play a major role in initiating the trypomastigote differentiation.

Sources of variation in locomotor activity and stereotypy in rats treated with d-amphetamine.

Rats injected with doses of d-amphetamine 0--5.0 mg/kg were observed continuously in either an enclosed Y-maze or on an elevated Y-shaped platform. Patterns of increased walking and stereotypy were unaffected by the type of apparatus, but rearing remained totally suppressed at all dose levels on the elevated platform. In the second experiment, groups of rats where given single short tests in the enclosed Y-maze, which was novel to them. The stimulant actions of d-amphetamine on locomotion were obscured by high baseline levels of motor activity induced by the novel environment. Continuous measurements of habituated rats may provide a more sensitive means of evaluating stimulant actions of drugs in screening tests. The observed changes in patterns of onset and offset of increased locomotion and of stereotypy were consistent with the view that these types of behaviour are, to some extent, independently, mediated.

Trypanosoma cruzi: endocytosis and degradation of specific antibodies by parasite forms.

Specific human IgG antibodies bound to a Trypanosoma cruzi envelope were internalized by antigen receptor-mediated endocytosis. Ferritin conjugated antibodies and horseradish peroxidase (HRP) conjugated IgG were found inside parasite cytoplasmic vesicles. Nonspecific IgG that did not bind to the external membrane was not internalized by the parasite. The ratio of 3H-protein A labeled: specific IgG internalization by parasites in the exponential growth phase (95% epimastigotes) was much smaller than that of parasites in the late stationary growth phase (38% trypomastigotes). Antibodies bound to the latter parasite forms almost disappeared from their outer membranes after 12 hr incubation at 27 degrees C. Results of experiments in which membrane bound antibodies were removed by an excess of pronase showed that only small amounts of radiolabeled IgG were found inside the parasites. The fate of immunoglobulins that vanished from external membrane receptors and did not accumulate inside the cells was explained by experiments in which the supernatants of IgG-3H-protein A labeled parasites were precipitated with trichloroacetic acid (TCA). In these, membrane-bound antibodies were taken in and degraded by the parasites as increased amounts of free radiolabel appeared in the supernatants as functions of incubation time and parasite stage.

Effect of immunotoxins against Trypanosoma cruzi.

Immunotoxins were constructed with IgG antibodies against Trypanosoma cruzi surface antigens by hybridization with abrin (ITA) and ricin (ITR) A chains. The biological activity of the hybrid macromolecules was tested on the parasite forms. Motility of parasite forms was lost in vitro after incubation with ITR. In general, killing of the parasite with ITR was more efficient than with ITA. Inhibition of protein synthesis after incubation with either ITR or ITA, measured by 3H-leucine incorporation, confirmed the parasite immobilization experiments. The lethal effect was potentiated when the immunotoxins were used in the presence of 2.5 mM ammonium chloride. T. cruzi antibodies specific to cell surface antigens are excellent drug carriers that can be delivered to the target cell. However, ITR and ITA did not reduce parasitemia or increase survival of mice infected with T. cruzi.

Virulence and pathogenicity associated with diversity of Trypanosoma cruzi stocks and clones derived from Chagas' disease patients.

The intraspecific variation that has been described in Trypanosoma cruzi was examined in recent isolates from Chagas' disease patients, using behavioral and molecular markers for characterization of the parasite stocks and derived clones. We used these parasite populations to determine virulence and pathogenicity in vivo. The T.cruzi stocks mSLU142 (megaesophagus) and hSLU239 (heart disease) and the clones h1 and h2 induced very low parasitemias in BALB/c mice, whereas high parasitemias were obtained with clones m1, m2, m3, and m4. Clones m1-m4 also produced heart lesions of higher intensity than those observed in mice infected with the h1 and h2 clones. Furthermore, the heart lesions produced by all of these clones were significantly more intense than those seen in mice infected with either of the T. cruzi parental stocks. In addition, neither the kinetics of growth, doubling time, differentiation in axenic culture, zymodemes, nor DNA restriction length polymorphisms showed correlations with parasitemias and pathogenicity in mice. This study suggests that multiple biochemical and physiological markers are required to enable an association of clinical and pathologic manifestations of the disease with intrinsic characters of the T. cruzi populations.

Chagas' disease: lymphoma growth in rabbits treated with Benznidazole.

Administration of the trypanocidal drug, Benznidazole (N-benzyl-2-nitro-imidazoleacetamide) to Trypanosoma cruzi-infected rabbits did not arrest the destructive Chagas' heart myocarditis. A typical feature of lymphocytic infiltrates associated with non-parasitized heart cell lysis was present in both treated and untreated groups of rabbits. Benznidazole-treated rabbits had their survival time shortened, probably as a consequence of Chagas' heart disease and of the development of lymphomas. The survival time of untreated T. cruzi-infected rabbits was 765 +/- 639 days and those treated with Benznidazole in the chronic phase of infection survived for 392 +/- 571 days. Malignant, non-Hodgkin's lymphomas were present in 38% of the rabbits that received the nitroarene therapy. Testicular atrophy was observed in 2 out of 10 nitroarene-treated rabbits. Benznidazole administration caused severe cell-mediated immunosuppression in T. cruzi-infected and BCG-immunized rabbits. Specific antibodies against the parasite and an unrelated antigen were detected in high levels, regardless of the nitroarene administration.

Genetic epidemiology of seropositivity for Trypanosoma cruzi infection in rural Goias, Brazil.

Chagas' disease is a zoonotic disease found throughout Latin America. Despite control programs in many of the affected countries, infection with Trypanosoma cruzi continues to be a major public health concern. In Brazil alone, approximately 53 million people live in endemic areas. Research with humans and with animal models indicates that there is variation in susceptibility to infection with T. cruzi. The reasons for this variation are not known although several studies have implicated genetic factors. An indirect immunofluorescence assay was used to assess seropositivity for T. cruzi infection in 716 adults from the municipality of Posse, Goias, Brazil. Detailed genealogic information was gathered at the time of sampling, which allowed assignment of 525 individuals to 146 pedigrees containing between two and 103 individuals; the remaining 191 unrelated individuals were retained as independents in the analysis. Using a maximum likelihood variance decomposition approach, we performed quantitative genetic analyses to determine if genetic factors could partially account for the observed pattern of seropositivity. The maximum likelihood estimate of the heritability of T. cruzi infection was 0.56 +/- 0.27 (mean +/- SE), indicating that genetic factors account for more than half of the observed variation in infection status. An additional 23% of the variation (c2 = 0.23 +/- 0.09) is attributable to the effects of shared environment, as assessed by common household. The results indicate that genetic factors play an important role in determining epidemiologic patterns of T. cruzi infection. Further characterization of these genetic factors may suggest new biologic areas to be targeted by prevention and intervention programs.