Cardiorespiratory abnormalities in ICU survivors of COVID-19 with postacute sequelae of SARS-CoV-2 infection are unrelated to invasive mechanical ventilation.

Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) often leads to exertional intolerance and reduced exercise capacity, particularly in individuals previously admitted to an intensive care unit (ICU). However, the impact of invasive mechanical ventilation (IMV) on PASC-associated cardiorespiratory abnormalities during exercise remains poorly understood. This single-center, cross-sectional study aimed to gather knowledge on this topic. Fifty-two patients with PASC recruited ∼6 mo after ICU discharge were clustered based on their need for IMV (PASC + IMV, n = 27) or noninvasive support therapy (PASC + NIS, n = 25). Patients underwent pulmonary function and cardiopulmonary exercise testing (CPX) and were compared with a reference group (CONTROL, n = 19) comprising individuals of both sexes with similar age, comorbidities, and physical activity levels but without a history of COVID-19 illness. Individuals with PASC, irrespective of support therapy, presented with higher rates of cardiorespiratory abnormalities than CONTROL, especially dysfunctional breathing patterns, dynamic hyperinflation, reduced oxygen uptake and oxygen pulse, and blunted heart rate recovery (all P < 0.05). Only the rate of abnormal oxygen pulse was greater among PASC + IMV group than PASC + NIS group (P = 0.05). Mean estimates for all CPX variables were comparable between PASC + IMV and PASC + NIS groups (all P > 0.05). These findings indicate significant involvement of both central and peripheral factors, leading to exertional intolerance in individuals with PASC previously admitted to the ICU, regardless of their need for IMV.NEW & NOTEWORTHY We found cardiorespiratory abnormalities in ICU survivors of severe-to-critical COVID-19 with PASC to be independent of IMV need. Overall, both group of patients experienced dysfunctional breathing patterns, dynamic hyperinflation, lower oxygen uptake and oxygen pulse, and blunted heart rate responses to CPX. PASC seems to impact exertional tolerance and exercise capacity due to ventilatory inefficiency, impaired aerobic metabolism, and potential systolic and autonomic dysfunction, all of these irrespective of support therapy during ICU stay.

The recombinant L-lysine α-oxidase from the fungus Trichoderma harzianum promotes apoptosis and necrosis of leukemia CD34 + hematopoietic cells.

BACKGROUND: In hematologic cancers, including leukemia, cells depend on amino acids for rapid growth. Anti-metabolites that prevent their synthesis or promote their degradation are considered potential cancer treatment agents. Amino acid deprivation triggers proliferation inhibition, autophagy, and programmed cell death. L-lysine, an essential amino acid, is required for tumor growth and has been investigated for its potential as a target for cancer treatment. L-lysine α-oxidase, a flavoenzyme that degrades L-lysine, has been studied for its ability to induce apoptosis and prevent cancer cell proliferation. In this study, we describe the use of L-lysine α-oxidase (LO) from the filamentous fungus Trichoderma harzianum for cancer treatment. RESULTS: The study identified and characterized a novel LO from T. harzianum and demonstrated that the recombinant protein (rLO) has potent and selective cytotoxic effects on leukemic cells by triggering the apoptotic cascade through mitochondrial dysfunction. CONCLUSIONS: The results support future translational studies using the recombinant LO as a potential drug for the treatment of leukemia.

Trehalose Improved 20-min Cycling Time-Trial Performance After 100-min Cycling in Amateur Cyclists.

Carbohydrate (CHO) supplementation during endurance exercise can improve performance. However, it is unclear whether low glycemic index (GI) CHO leads to differential ergogenic and metabolic effects compared with a standard high GI CHO. This study investigated the ergogenic and metabolic effects of CHO supplementation with distinct GIs, namely, (a) trehalose (30 g/hr), (b) isomaltulose (30 g/hr), (c) maltodextrin (60 g/hr), and (d) placebo (water). In this double-blind, crossover, counterbalanced, placebo-controlled study, 13 male cyclists cycled a total of 100 min at varied exercise intensity (i.e., 10-min stages at 1.5, 2.0, and 2.5 W/kg; repeated three times plus two 5-min stages at 1.0 W/kg before and after the protocol), followed by a 20-min time trial on four separated occasions. Blood glucose and lactate (every 20 min), heart rate, and ratings of perceived exertion were collected throughout, and muscle biopsies were taken before and immediately after exercise. The results showed that trehalose improved time-trial performance compared with placebo (total work done 302 ± 39 vs. 287 ± 48 kJ; p = .01), with no other differences between sessions (all p ≥ .07). Throughout the 100-min protocol, blood glucose was higher with maltodextrin compared with the other supplements at all time points (all p < .05). Heart rate, ratings of perceived exertion, muscle glycogen content, blood glucose, and lactate were not different between conditions when considering the 20-min time trial (all p > .05). Trehalose supplementation throughout endurance exercise improved cycling performance and appears to be an appropriate CHO source for exercise tasks up to 2 hr. No ergogenic superiority between the different types of CHO was established.

Combining Near-Infrared Spectroscopy and Heart Rate Variability Derived Thresholds to Estimate the Critical Intensity of Exercise.

ABSTRACT: Fleitas-Paniagua, PR, de Almeida Azevedo, R, Trpcic, M, Murias, JM, and Rogers, B. Combining near-infrared spectroscopy and heart rate variability derived thresholds to estimate the critical intensity of exercise. J Strength Cond Res 38(1): e16-e24, 2024-Critical intensity determination often requires costly tools and several testing sessions. Alternative approaches display relatively large individual variation. Therefore, simpler estimations with improved precision are needed. This study evaluated whether averaging the heart rate (HR) and oxygen uptake (V̇O 2 ) responses associated with the muscle deoxyhemoglobin concentration breakpoint ([HHb] BP ) and the heart rate variability (HRV) given by the detrended fluctuation analysis second threshold (HRVT2) during ramp incremental (RI) test improved the accuracy of identifying the HR and V̇O 2 at the respiratory compensation point (RCP). Ten female and 11 male recreationally trained subjects performed a 15 W·minute -1 RI test. Gas exchange, near-infrared spectroscopy (NIRS), and RR interval were recorded to assess the RCP, [HHb] BP , and HRVT2. Heart rate (mean ± SD : 158 ± 14, 156 ± 13, 160 ± 14 and, 158 ± 12 bpm) and V̇O 2 (3.08 ± 0.69, 2.98 ± 0.58, 3.06 ± 0.65, and 3.02 ± 0.60 L·minute -1 ) at the RCP, [HHb] BP , HRVT2, and HRVT2&[HHb] BP average (H&H Av ), respectively, were not significantly different ( p > 0.05). The linear relationship between H&H Av and RCP was higher compared with the relationship between [HHb] BP vs RCP and HRVT2 vs RCP for both HR ( r = 0.85; r = 0.73; r = 0.79, p > 0.05) and V̇O 2 ( r = 0.94; r = 0.93; r = 0.91, p > 0.05). Intraclass correlation between RCP, [HHb] BP , HRVT2, and H&H AV was 0.93 for V̇O 2 and 0.79 for HR. The [HHb] BP and the HRVT2 independently provided V̇O 2 and HR responses that strongly agreed with those at the RCP. Combining [HHb] BP and the HRVT2 resulted in estimations of the V̇O 2 and HR at the RCP that displayed smaller variability compared with each modality alone.

Paracoccin Overexpression in Paracoccidioides brasiliensis Enhances Fungal Virulence by Remodeling Chitin Properties of the Cell Wall.

BACKGROUND: The thermodimorphic fungi Paracoccidioides spp. are the etiological agents of paracoccidioidomycosis. Although poorly studied, paracoccin (PCN) from Paracoccidioides brasiliensis has been shown to harbor lectinic, enzymatic, and immunomodulatory properties that affect disease development. METHODS: Mutants of P. brasiliensis overexpressing PCN (ov-PCN) were constructed by Agrobacterium tumefaciens-mediated transformation. ov-PCN strains were analyzed and inoculated intranasally or intravenously to mice. Fungal burden, lung pathology, and survival were monitored to evaluate virulence. Electron microscopy was used to evaluate the size of chito-oligomer particles released by ov-PCN or wild-type strains to growth media. RESULTS: ov-PCN strains revealed no differences in cell growth and viability, although PCN overexpression favored cell separation, chitin processing that results in the release of smaller chito-oligomer particles, and enhanced virulence. Our data show that PCN triggers a critical effect in the cell wall biogenesis through the chitinase activity resulting from overexpression of PCN. As such, PCN overexpression aggravates the disease caused by P. brasiliensis. CONCLUSIONS: Our data are consistent with a model in which PCN modulates the cell wall architecture via its chitinase activity. These findings highlight the potential for exploiting PCN function in future therapeutic approaches.

Effects of induced local ischemia during a 4-km cycling time trial on neuromuscular fatigue development.

The present study analyzed the effects of local ischemia during endurance exercise on neuromuscular fatigue (NMF). Nine cyclists performed, in a counterbalanced order, two separate 4-km cycling time trials (TT) with (ISCH) or without (CONTR) induced local ischemia. NMF was characterized by using isometric maximal voluntary contractions (IMVC), whereas central [voluntary activation (VA)] and peripheral fatigue [peak torque of potentiated twitch (TwPt)] of knee extensors were evaluated using electrically evoked contractions performed before (PRE) and 1 min after (POST) the TT. Electromyographic activity (EMG), power output (PO), oxygen uptake (V̇o2), and rating of perceived exertion (RPE) were also recorded. The decrease in IMVC (-15 ± 9% vs. -10 ± 8%, P = 0.66), VA (-4 ± 3% vs. -3 ± 3%, P = 0.46), and TwPt (-16 ± 7% vs. -19 ± 14%, P = 0.67) was similar in ISCH and CONTR. Endurance performance was drastically reduced in ISCH condition (512 ± 29 s) compared with CONTR (386 ± 17 s) (P < 0.001), which was accompanied by lower EMG, PO, and V̇o2 responses (all P < 0.05). RPE was greater in ISCH compared with CONTR (P < 0.05), but the rate of change was similar throughout the TT (8.19 ± 2.59 vs. 7.81 ± 2.01 RPE.% of total time-1, P > 0.05). These results indicate that similar end-exercise NMF levels were accompanied by impaired endurance performance in ISCH compared with CONTR. These novel findings suggest that the local reduced oxygen availability affected the afferent feedback signals to the central nervous system, ultimately increasing perceived effort and reducing muscle activity and exercise intensity to avoid surpassing a sensory tolerance limit before the finish line.

Neurological disease caused by Oropouche virus in northern Brazil: should it be included in the scope of clinical neurological diseases?

We describe two neurological cases of Oropouche virus infection in northern Brazil, where the virus is endemic but neglected as a pathogen. This study reiterates the necessity of developing protocols for diagnosing infections and training medical personnel to recognize the pathogenicity of Oropouche virus in neurological infections.

International Medical Graduates are Comparable to American Medical Graduates as General Surgery Interns.

BACKGROUND: International medical graduates (IMGs) are often relegated to preliminary positions in general surgery (GS) owing to uncertainties about the candidate's performance in the American healthcare setting. We aimed to determine the comparative performance of IMGs and American medical graduates (AMGs) at baseline and assess these trends over the course of their GS internship. METHODS: Evaluations of all IMG preliminary and AMG categorical interns from 2013 to 2017 at our GS residency program were obtained from three faculty members to score overall performance, technical skills, interpersonal communication, and medical knowledge on a 10-point Likert scale. Scores on the American Board of Surgery In-Training Exam, an in-house preparation test, United States Medical Licensing Exam, and performance during the biannual multistation objective assessments were compared between the two resident groups. RESULTS: Seventy-two interns (28 [39%] AMG categorical and 44 [61%] IMG preliminary) met inclusion criteria. The AMG group had significantly higher median Step 1 and Step 2 scores compared with our IMG group (243 versus 231, P = 0.002, and 250 versus 246, P = 0.03, respectively).Although in-house preparation test scores were higher among IMGs (median [interquartile range] of 36 [33-40] among AMGs and 38 [34-45] among IMGs; P = 0.002), there were no statistically significant differences between the American Board of Surgery In-Training Exam scores of the two groups. The median scores for the four faculty evaluation components were similar between the AMG (7, 8, 7, 7) and IMG resident groups (7, 7, 7, 7; P = nonsignificant). IMGs scored significantly higher in both biannual multistation objective assessments than AMGs (median [interquartile range] July: 59 [47-91] versus 55 [37-62], P = 0.005; January: 103 [86-116] versus 91 [87-104], P = 0.03). CONCLUSIONS: It is reassuring to confirm that no matter where they are from, great candidates can perform well as surgical interns in a GS training program.

Prolonged Mechanical Ventilation in Children: Review of the Definition.

OBJECTIVES: To review existing definitions of prolonged mechanical ventilation in children. DESIGN: Review of the literature. SETTING: Not applicable. PATIENTS: Pediatric patients under mechanical ventilation. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: We searched the literature for original research on prolonged mechanical ventilation in children using the PubMed, Embase, and Cochrane Library databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and we extracted patient characteristics, duration of mechanical ventilation, outcomes, and associated complications. We identified 30 articles for qualitative analysis and found a wide variety of definitions, varying from 48 hours to 6 months. The most frequently used definitions of prolonged mechanical ventilation were greater than 7 days, greater than 14 days, and greater than 21 days. There was no high-quality evidence of a definition for prolonged mechanical ventilation in children. CONCLUSIONS: There is limited evidence to determine the definition of prolonged mechanical ventilation in children. The variety of definitions is a sign of the need for a consensus definition of pediatric prolonged mechanical ventilation.

Fatigue development and perceived response during self-paced endurance exercise: state-of-the-art review.

Performance in self-paced endurance exercises results from continuous fatigue symptom management. While it is suggested that perceived responses and neuromuscular fatigue development may determine variations in exercise intensity, it is uncertain how these fatigue components interact throughout the task. To address the fatigue development in self-paced endurance exercises, the following topics were addressed in the present review: (1) fatigue development during constant-load vs. self-paced endurance exercises; (2) central and peripheral fatigue and perceived exertion interconnections throughout the self-paced endurance exercises; and (3) future directions and recommendations. Based on the available literature, it is suggested (1) the work rate variations during a self-paced endurance exercise result in transitions between exercise intensity domains, directly impacting the end-exercise central and peripheral fatigue level when compared to constant-load exercise mode; (2) central and peripheral fatigue, as well as perceived exertion response contribute to exercise intensity regulation at the different stages of the trial. It seems that while neuromuscular fatigue development might be relevant at beginning of the trial, the perceived exertion might interfere in the remaining parts to achieve maximal values only at the finish line; (3) future studies should focus on the mechanisms underpinning fatigue components interactions throughout the task and its influence on exercise intensity variations.

The effect of the fraction of inspired oxygen on the NIRS-derived deoxygenated hemoglobin "breakpoint" during ramp-incremental test.

During ramp-incremental (RI) exercise to exhaustion, the near-infrared spectroscopy-derived deoxygenated hemoglobin ([HHb]) signal in the vastus lateralis muscle shows a linear increase up to a point at which a plateau-like response is manifested ([HHb]bp). This study investigated if 1) the [HHb]bp is affected by different fractions of inspired O2 (FIO2) [hypoxia (16%; HYPO); normoxia (21%; NORM); hyperoxia (30%; HYPER)]; and 2) an abrupt change to hyperoxic-inspired gas just before the occurrence of the [HHb]bp (HYPERSWITCH) would affect the [HHb] plateau-like response. Ten physically active male participants reported to the laboratory on four separate occasions to perform an RI test to exhaustion in NORM, HYPO, and HYPER and an RI test to exhaustion with an abrupt increase in FIO2 (30%; HYPERSWITCH) 15 W before the power output (PO) associated with [HHb]bp in normoxia. PO, [HHb], tissue O2 (StO2), and pulse O2 saturation (SpO2) were recorded continuously. Peak PO was significantly lower in HYPO (290 ± 21 W) and higher in HYPER (321 ± 22 W) and HYPERSWITCH (320 ± 19 W) compared with NORM (311 ± 18 W). The PO associated with [HHb]bp was not different between NORM and HYPER (246 ± 23 vs. 247 ± 24 W), but it was lower in HYPO (198 ± 31 W) than NORM and HYPER. The PO associated with the [HHb]bp in HYPERSWITCH (240 ± 23) was not different compared with NORM. HYPER and HYPERSWITCH resulted in greater StO2 and SpO2 compared with NORM. These results suggest that the [HHb]bp response is not dependent of O2 driving pressure and that other physiological mechanisms might determine its occurrence.

Evaluating the suitability of supra-POpeak verification trials after ramp-incremental exercise to confirm the attainment of maximum O2 uptake.

During exhaustive ramp-incremental cycling tests, the incidence of O2 uptake (V̇o2) plateaus is low. To verify the attainment of maximum V̇o2 (V̇o2max), it is recommended that a trial at a power output (PO) corresponding to 110% of the ramp-derived peak (POpeak) is performed. It remains unclear whether verification trials set at this PO can be tolerated for long enough to allow attainment of V̇o2max. Eleven recreationally trained individuals performed five ramp tests of varying slope (5, 10, 15, 25, and 30 W/min), each followed, in series, by two verification trials: the first at 110% POpeak of the 25 W/min ramp and the second at 110% POpeak attained in the preceding ramp test. Exercise duration of the first verification trial was on average 81 ± 15 s (CV = 9 ± 3%) versus 162 ± 32, 121 ± 24, 103 ± 15, and 73 ± 10 s for the second verification trials at 110% of POpeak of the 5, 10, 15, and 30 W/min ramp tests, respectively (P < 0.05). Compared with the highest V̇o2 recorded during ramp tests, V̇o2 from the subsequent verification trials was not different for the 5, 10, and 15 W/min ramp tests (P > 0.05) but was lower for the 25 and 30 W/min ramp tests (P < 0.05). Verification trials at 110% POpeak of rapidly incrementing ramp tests (i.e., 25 W/min) were not sustained for long enough to allow the attainment of V̇o2max. With commonly used rapidly incrementing ramp tests engendering exhaustion within 8-12 min, verification trials less than POpeak should be preferred as they can be sustained sufficiently long to allow the attainment of V̇o2max.

Clinical significance of SLN benign capsular nevi in patients with melanoma.

BACKGROUND: Benign capsular nevi (BCN) are not infrequent in sentinel lymph nodes (SLN) of patients with melanoma. Their prognostic significance is unknown and the literature is limited. This study evaluated the clinical significance of incidentally found BCN in these patients. METHODS: A multi-institutional retrospective review of patients undergoing SLN biopsy for cutaneous melanoma between 2000 and 2016. Patients were divided into the following groups: (a) negative SLN and no BCN, (b) negative SLN and presence of BCN, (c) positive SLN seen only on immunohistochemistry (IHC), and (d) positive SLN via hematoxylin and eosin (H&E). Outcomes measured were overall survival and any recurrence. RESULTS: A total of 1253 patients were identified (group 1 = 978, group 2 = 56, group 3 = 32, and group 4 = 187). Fifty-seven percent were male and the mean age was 59.3 years. BCN was identified in 77 patients (6.2%), of which the majority was in the node-negative group (72%). Multivariable analysis showed that BCN was associated with lower recurrence rates, though not statistically significant (hazard ratio [HR] = 0.5; P = .06). IHC- and H&E-positive SLNs were associated with a higher risk of recurrence (HR = 2.4; P = .02 and 2.0, P < .0001, respectively). CONCLUSION: Patients with BCN and negative SLN had lower recurrence rates than patients with negative SLN and no BCN. Our data suggest a possible protective effect against recurrence.

Brazilian Society of Surgical Oncology guidelines for surgical treatment of endometrial cancer in regions with limited resources.

BACKGROUND: Approximately 70% of cancer-related deaths occur in low- and middle-income countries. In addition to social and racial inequalities, treatment options in these countries are usually limited because of the lack of trained staff and equipment, limited patient access to health services, and a small number of clinical guidelines. OBJECTIVES: The Brazilian Society of Surgical Oncology developed this guideline to address these barriers and guide physicians treating patients with endometrial cancer (EC) in regions with limited resources and few specialized centers. METHODS: The guideline was prepared from 10 January to 25 October 20192019 by a multidisciplinary team of 56 experts to discuss the main obstacles faced by EC patients in Brazil. Thirteen questions considered critical to the surgical treatment of these patients were defined. The questions were assigned to groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments for presentations in meetings, classified the level of evidence, and voted on the recommendations. RESULTS: For all questions including staging, fertility spearing treatment, genetic testing, sentinel lymph node use, surgical treatment, and other clinical relevant questions, major agreement was achieved by the participants, always using accessible alternatives. CONCLUSIONS: It is possible to provide adequate treatment for most EC patients in resource-limited areas, but the first option should be referral to specialized centers with more resources.

Citation Skew in Plastic Surgery Journals: Does the Journal Impact Factor Predict Individual Article Citation Rate?

BACKGROUND: Citation skew refers to the unequal distribution of citations to articles published in a particular journal. OBJECTIVES: We aimed to assess whether citation skew exists within plastic surgery journals and to determine whether the journal impact factor (JIF) is an accurate indicator of the citation rates of individual articles. METHODS: We used Journal Citation Reports to identify all journals within the field of plastic and reconstructive surgery. The number of citations in 2018 for all individual articles published in 2016 and 2017 was abstracted. RESULTS: Thirty-three plastic surgery journals were identified, publishing 9823 articles. The citation distribution showed right skew, with the majority of articles having either 0 or 1 citation (40% and 25%, respectively). A total of 3374 (34%) articles achieved citation rates similar to or higher than their journal's IF, whereas 66% of articles failed to achieve a citation rate equal to the JIF. Review articles achieved higher citation rates (median, 2) than original articles (median, 1) (P < 0.0001). Overall, 50% of articles contributed to 93.7% of citations and 12.6% of articles contributed to 50% of citations. A weak positive correlation was found between the number of citations and the JIF (r = 0.327, P < 0.0001). CONCLUSIONS: Citation skew exists within plastic surgery journals as in other fields of biomedical science. Most articles did not achieve citation rates equal to the JIF with a small percentage of articles having a disproportionate influence on citations and the JIF. Therefore, the JIF should not be used to assess the quality and impact of individual scientific work.

Production and Uptake of Distinct Endogenous Catecholate-Type Siderophores Are Required for Iron Acquisition and Virulence in Chromobacterium violaceum.

Bacteria use siderophores to scavenge iron from environmental or host sources. The iron acquisition systems of Chromobacterium violaceum, a ubiquitous environmental bacterium that can cause infections in humans, are still unknown. In this work, we demonstrated that C. violaceum produces putative distinct endogenous siderophores, here named chromobactin and viobactin, and showed that they are each required for iron uptake and virulence. An in silico analysis in the genome of C. violaceum revealed that genes related to synthesis and uptake of chromobactin (cba) and viobactin (vba) are located within two secondary-metabolite biosynthetic gene clusters. Using a combination of gene deletions and siderophore detection assays, we revealed that chromobactin and viobactin are catecholate siderophores synthesized from the common precursor 2,3-dihydroxybenzoate (2,3-DHB) on two nonribosomal peptide synthetase (NRPS) enzymes (CbaF and VbaF) and taken up by two TonB-dependent receptors (CbuA and VbuA). Infection assays in mice revealed that both the synthesis and the uptake of chromobactin or viobactin are required for the virulence of C. violaceum, since only the mutant strains that do not produce any siderophores or are unable to take up both of them were attenuated for virulence. In addition, the mutant strain unable to take up both siderophores showed a pronounced attenuation of virulence in vivo and reduced neutrophil extracellular trap (NET) formation in in vitro assays, suggesting that extracellularly accumulated siderophores modulate the host immune response. Overall, our results revealed that C. violaceum uses distinct endogenous siderophores for iron uptake and its establishment in the host.

How Reliable Is CT Scan in Staging Right Colon Cancer?

BACKGROUND: The observation of inferior oncologic outcomes after surgery for proximal colon cancers has led to the investigation of alternative treatment strategies, including surgical procedures and neoadjuvant systemic chemotherapy in selected patients. OBJECTIVE: The purpose of this study was to determine the accuracy of CT staging in proximal colon cancer in detecting unfavorable pathologic features that may aid in the selection of ideal candidates alternative treatment strategies, including extended lymph node dissection and/or neoadjuvant chemotherapy. DESIGN: This was a retrospective consecutive series. SETTINGS: Trained abdominal radiologists from 2 centers performed a blinded review of CT scans obtained to locally stage proximal colon cancer according to previously defined prognostic groups, including T1/2, T3/4, N+, and extramural venous invasion. CT findings were compared with histopathologic results as a reference standard. Unfavorable pathologic findings included pT3/4, pN+, or extramural venous invasion. PATIENTS: Consecutive patients undergoing right colectomy in 2 institutions between 2011 and 2016 were retrospectively reviewed from a prospectively collected database. MAIN OUTCOME MEASURES: T status, nodal status, and extramural venous invasion status comparing CT with final histologic findings were measured. RESULTS: Of 150 CT scans reviewed, CT failed to identify primary cancer in 18%. Overall accuracy of CT to identify unfavorable pathologic features was 63% with sensitivity, specificity, positive predictive value, and negative predictive value of 63% (95% CI, 54%-71%), 63% (95% CI, 46%-81%), 87% (95% CI, 80%-94%) and 30% (95% CI, 18%-41%). Only cT3/4 (55% vs 45%; p = 0.001) and cN+ (42% vs 58%; p = 0.02) were significantly associated with correct identification of unfavorable features at final pathology. CT scans overstaged and understaged cT in 23.7% and 48.3% and cN in 28.7% and 53.0% of cases. LIMITATIONS: The study was limited by its retrospective design, relatively small sample size, and heterogeneity of CT images performed in different institutions with variable equipment and technical details. CONCLUSIONS: Accuracy of CT scan for identification of pT3/4, pN+, or extramural venous invasion was insufficient to allow for proper identification of patients at high risk for local recurrence and/or in whom to consider alternative treatment strategies. Locoregional overstaging and understaging resulted in inappropriate treatment strategies in <48%. See Video Abstract at http://links.lww.com/DCR/A935.

Stretch-shortening cycle exercise produces acute and prolonged impairments on endurance performance: is the peripheral fatigue a single answer?

OBJECTIVE: This study aimed to verify the acute and prolonged effects of stretch-shortening cycle exercise (SSC) on performance and neuromuscular function following a 4-km cycling time trial (4-km TT). METHODS: On separate days, individuals performed a 4-km TT without any previous exercise (CON), immediately (ACUTE) and 48 h after (PROL) SSC protocol (i.e., 100-drop jumps). Neuromuscular function was measured at baseline SSC (baseline), before (pre-TT) and after (post-TT) 4-km TT. Muscle soreness and inflammatory responses also were assessed. RESULTS: The endurance performance was impaired in both ACUTE (- 2.3 ± 1.8%) and PROL (- 1.8 ± 2.4%) compared with CON. The SSC protocol caused also an acute reduction in neuromuscular function, with a greater decrease in potentiated quadriceps twitch-force (Qtw.pot - 49 ± 16%) and voluntary activation (VA - 6.5 ± 7%) compared for CON and PROL at pre-TT. The neuromuscular function was fully recovered 48 h after SSC protocol. Muscle soreness and IL-10 were elevated only 48 h after SSC protocol. At post-TT, Qtw.pot remained lower in ACUTE (- 52 ± 14%) compared to CON (- 29 ± 7%) and PROL (- 31 ± 16%). CONCLUSION: These findings demonstrate that impairment in endurance performance induced by prior SSC protocol was mediated by two distinct mechanisms, where the acute impairment was related to an exacerbated degree of peripheral and central fatigue, and the prolonged impairment was due to elevated perceived muscle soreness.

Receptor Heterodimerization and Co-Receptor Engagement in TLR2 Activation Induced by MIC1 and MIC4 from Toxoplasma gondii.

The microneme organelles of Toxoplasma gondii tachyzoites release protein complexes (MICs), including one composed of the transmembrane protein MIC6 plus MIC1 and MIC4. In this complex, carbohydrate recognition domains of MIC1 and MIC4 are exposed and interact with terminal sialic acid and galactose residues, respectively, of host cell glycans. Recently, we demonstrated that MIC1 and MIC4 binding to the N-glycans of Toll-like receptor (TLR) 2 and TLR4 on phagocytes triggers cell activation and pro-inflammatory cytokine production. Herein, we investigated the requirement for TLR2 heterodimerization and co-receptors in MIC-induced responses, as well as the signaling molecules involved. We used MICs to stimulate macrophages and HEK293T cells transfected with TLR2 and TLR1 or TLR6, both with or without the co-receptors CD14 and CD36. Then, the cell responses were analyzed, including nuclear factor-kappa B (NF-κB) activation and cytokine production, which showed that (1) only TLR2, among the studied factors, is crucial for MIC-induced cell activation; (2) TLR2 heterodimerization augments, but is not critical for, activation; (3) CD14 and CD36 enhance the response to MIC stimulus; and (4) MICs activate cells through a transforming growth factor beta-activated kinase 1 (TAK1)-, mammalian p38 mitogen-activated protein kinase (p38)-, and NF-κB-dependent pathway. Remarkably, among the studied factors, the interaction of MIC1 and MIC4 with TLR2 N-glycans is sufficient to induce cell activation, which promotes host protection against T. gondii infection.

Mental fatigue does not alter performance or neuromuscular fatigue development during self-paced exercise in recreationally trained cyclists.

PURPOSE: The purpose of this study was to investigate the effects of mental fatigue, characterized by a subjective feeling of tiredness, on the development of neuromuscular fatigue during a 4-km cycling time trial (4-km TT). METHODS: Eight recreationally trained male cyclists performed a 4-km TT after either performing a prolonged cognitive task (mental fatigue) or after viewing emotionally neutral documentaries (control). The neuromuscular function of the knee extensors was assessed using electrical nerve stimulation at baseline, before (pre-TT), and after (post-TT) the 4-km TT. Rating of perceived exertion (RPE) and physiological variables were periodically measured during 4-km TT. RESULTS: Subjective ratings of fatigue increased significantly only after a prolonged cognitive task (P = 0.022). Neuromuscular function at baseline was similar between conditions and remained unchanged at pre-TT. Time to complete the 4-km TT was similar between control (376 ± 27 s) and mental fatigue (376 ± 26 s). There was no significant difference between conditions for RPE, [Formula: see text], [Formula: see text], and HR throughout the exercise. The 4-km TT-induced similar decrease (from baseline to post-TT) in maximal voluntary contraction (mental fatigue - 11 ± 10%, control - 16 ± 12%), twitch force (mental fatigue - 26 ± 16%, control - 24 ± 17%), and voluntary activation (mental fatigue - 5 ± 7%, control - 3 ± 2%) for both conditions. CONCLUSION: Mental fatigue induced by prolonged cognitive task does not impair performance nor alter the degree of central and peripheral fatigue development during self-paced exercise in recreationally trained cyclists.