Miracle-dz/UniFAR-FTUs huggingface dataset:
Defining and measuring recovery from myalgic encephalomyelitis and chronic fatigue syndrome: the physician perspective

Abstract Purpose: To inform an operationalised definition of recovery from myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) for research and practice. Without a consensus on defining and measuring recovery, there will continue to be controversy amongst researchers, clinicians, and patients when interpreting treatment outcomes. Method: This study explores physicians’ views on recovery from ME and CFS. We conducted semi-structured interviews with 10 physician participants who are experts in the ME and CFS field. Our deductive thematic analysis, using a realist perspective, provided a framework for differentiating recovery and significant improvement. Results: Physicians conceptualised recovery as complete symptom remission and a return to premorbid functioning (adjusted for with age), whereas they viewed significant improvement as a substantial reduction in symptoms with considerable functional gains, where patients may operate in daily life but still must cope or be treated. Conclusions: Our findings provide recommendations and approaches for measuring: daily functioning, symptomatology, quality of life, and physical functioning. Implications for rehabilitation Physicians viewed recovery as complete symptom remission and a return to premorbid functioning (adjusted for with age). Recovery from myalgic encephalomyelitis and chronic fatigue syndrome should be viewed as multidimensional, considering patients’ daily life, psychosocial functioning, and overall physical functioning. These findings can improve practitioner-client interactions, as they provide recommendations for measuring recovery in research and practice.
Influence of Fractionated Total Body Irradiation on Mucosal Toxicity in Intensified Conditioning Regimens for Autologous Bone Marrow Transplantation in Pediatric Cancer Patients

From April 1988 to March 1991 28 children with generalized solid tumors (N = 15) or hematologic malignancies (N = 13) received intensified myelotoxic regimens followed by autologous stem cell rescue (ABMT). These intensified regimens consisted of 12 Gy fractionated total body irradiation (FTBI) and 2 (or 3) cytotoxic drugs (group A, n = 19) or a combination of 3 cytotoxic drugs (group B, n = 9). FTBI-containing regimens produced more severe mucositis > = WHO grade 3 (p = 0.01) and a longer duration of severe mucositis. The mucositis had a median duration of 8 days (range 0-28) in group A compared with median 0 days (range 0-7) in group B (p < 0.01). Acute renal and liver toxicity were not different. The probability of overall survival at day +100 was 89% in all patients. In terms of long-term survival FTBI containing regimen did not prove superior: 5 out of 19 patients in group A and 6 out of 9 patients in group B have been survivors for a minimum of 3 years. In conclusion, severe gastrointestinal toxicity of such intensive regimens is avoidable if FTBI is omitted.
Hypogonadal Mouse, a Model to Study the Effects of the Endogenous Lack of Gonadotropins on Apoptosis1

Abstract Testicular apoptosis is involved in the regulation of germ cell numbers, allowing optimal sperm production. Apoptosis has been described to occur in response to the absence of hormonal stimulation of the testis. Here we investigate the effect of the physiological lack of gonadotropins from birth using the hypogonadal (homozygous for the mutant allele Gnrh1hpg) mouse as a model. We pursued a concerted strategy using microarray analysis and RT-PCR to assess transcript levels, TUNEL to quantify the incidence of apoptosis, and Western blotting to assess the respective contribution of the extrinsic and intrinsic apoptotic pathways. Our results indicate a large increase in apoptosis of both somatic and germ cell compartments in the hpg testis, affecting Sertoli cells as well as germ cells of all ages. We confirmed our observations of Sertoli cell apoptosis using anti-Mullerian inhibiting substance staining and staining for cleaved fodrin alpha. In the somatic compartment, apoptosis is primarily regulated via the membrane receptor (extrinsic) apoptotic pathway, while in the germ cell compartment, regulation occurs via both the mitochondrial (intrinsic) and membrane receptor (extrinsic) apoptotic pathways, the latter potentially in a stage-specific manner. This study is the first report of spermatogonial apoptosis in response to gonadotropin deficiency as well as the first report of Sertoli cell apoptosis in response to gonadotropin deficiency in the mouse.
A meta-analysis of the facilitation of arm flexion and extension movements as a function of stimulus valence

This article presents a meta-analysis of research on the affective compatibility effect: the relative facilitation of arm flexion and extension movements, in response to positive and negative stimuli, respectively. Across 68 effect sizes (computed on 3169 participants), a small, significant average compatibility effect emerged (ES = .118; 95% CI [.051, .185]). Importantly, analyses also revealed significant heterogeneity in the set of effect sizes. Moderator analyses were conducted to explain this observed heterogeneity with a view to testing between extant theoretical accounts of the compatibility effect. Affective compatibility effects were significantly larger (1) for face stimuli than for words or pictorial stimuli; (2) when the negative stimuli partly comprising the effect were anger-related; (3) for responses made using vertical button press; (4) when situated aspects of the processing task framed flexion as approach and extension as avoidance; and (5) when explicit response labels framed flexion as positive and extension as negative. Significant reverse compatibility effects emerged (1) when aspects of the processing context framed flexion as avoidance and extension as approach and (2) when explicit response labels framed flexion as negative and extension as positive. The results of the meta-analysis provide little support for the strong embodiment, specific muscle activation account of affective compatibility and are broadly consistent with distance regulation, and, in particular, evaluative coding accounts.
Intraoperative Radiation Exposure During Hip Arthroscopy

Background: The frequency of hip arthroscopy for the treatment of acute and chronic chondrolabral pathology and femoroacetabular impingement (FAI) has increased exponentially over the past decade. While surgeon and patient radiation exposure has been well documented in other areas of the orthopaedic literature, little is known about the procedure-specific and cumulative doses affecting the hip arthroscopist. Purpose: To determine the mean annual radiation exposure to the hip arthroscopist and the mean surgeon exposure per case. Study Design: Case series; Level of evidence, 4. Methods: A total of 210 consecutive hip arthroscopies performed in 209 patients by a single surgeon at a single ambulatory surgical center in a cohort consisting of approximately 50% bony (cam and pincer) pathology were prospectively reviewed, documenting the specific procedures performed in each case and the readings from a radiation dosimeter worn by the surgeon during positioning and while performing the procedures. Radiation readings for deep dose–equivalent (DDE), lens dose–equivalent (LDE), and shallow dose–equivalent (SDE) were measured. These readings were compared with the annual radiation dose limit recommendations established by the International Commission on Radiological Protection (ICRP). Results: The total radiation doses for the operative surgeon during all 210 cases were 183 mrem (1.83 mSv) DDE, 183 mrem (1.83 mSv) LDE, and 176 mrem (1.76 mSv) SDE. The mean exposure per case was 0.871 mrem (0.00871 mSv) DDE, 0.871 mrem (0.00871 mSv) LDE, and 0.838 mrem (0.00838 mSv) SDE. The operative surgeon’s mean annual exposure, performing 70 hip arthroscopies per year with 55% involving bony work, was 61.0 mrem (0.610 mSv) DDE, 61.0 mrem (0.610 mSv) LDE, and 58.7 mrem (0.587 mSv) SDE. These results are well below the ICRP annual limits of 50,000 mrem (500 mSv) DDE, 2000 mrem (20 mSv) LDE, and 50,000 mrem (500 mSv) SDE. Conclusion: For an experienced hip arthroscopist utilizing fluoroscopy during setup and bony resection, the annual and per-patient exposure to radiation remains well below the recommended ICRP limits. Clinical Relevance: Considering the increasing annual frequency of hip arthroscopies being performed, information regarding procedure-specific and cumulative doses of radiation exposure affecting the hip arthroscopist may provide valuable safety information for the orthopaedic community.
Control of an AC Dynamometer for Dynamic Emulation of Mechanical Loads With Stiff and Flexible Shafts

This paper addresses the emulation of linear and nonlinear loads using a vector-controller dynamometer for the position control of mechanical loads. The emulation strategy allows an electrical machine (dynamometer) to be controlled, so as to emulate both the static and dynamic characteristics of a load with a certain bandwidth. The approach can be used for the experimental validation and testing of the electrical drives and motion-control techniques. The dynamic structure of the emulated load is always preserved. High-order systems such as loads with flexible shafts and nonlinear effects can be emulated accurately. This paper presents the dynamometer-control design, its practical implementation, and experimental results for the position control of the linear and nonlinear emulated loads. Systems with stiff and flexible shafts are considered. Finally, the experimental results are compared with the corresponding simulated loads to validate the emulation strategy
Digestive tract reconstitution after failed esophago-gastro or esophago-coloanastomosis.

BACKGROUND Severe dysphagia or even aphagia can occur after esophagectomy secondary to necrosis of the ascended organ with severe stricture or complete separation of the stumps. Catastrophic esophageal or gastric disruption drives the decision to "disconnect" the esophagus in order to prevent severe septic complications. The operations employed to re-establish esophageal discontinuity are not standardized and reoperations for re-establishment of the upper digestive transit are a real challenge. METHODS This is retrospective study collecting the authors experience during 17 years including 18 patients, 14 of them previously submitted to esophagectomy and four to esophagogastrectomy. They were operated on in order to re-establish the upper digestive tract. RESULTS Redo esophago-gastro-anastomosis was possible in 12 patients, 10 through cervical approach and combined with sternotomy in four in order to perform the new anastomosis. In five patients a new esophago-colo anastomosis was performed. Free jejunal graft interposition was performed in one patient. Complications occurred in ten patients (55.5 %): anastomotic leaks in three, strictures in four, sternal condritis in two and cervical abscess in one. No mortality was observed. CONCLUSION There are different surgical options for the treatment of this difficult and risky clinical situation which must be treated with tailored procedures according to the anatomic segment available to be used, choosing the most conservative procedure.
Complete plasmid sequence carrying type IV-like and type VII secretion systems from an atypical mycobacteria strain

The genus Mycobacterium is highly diverse and ubiquitous in nature, comprehending fast- and slow-growing species with distinct impact in public health. The plasmid-mediated horizontal gene transfer represents one of the major events in bacteria evolution. Here, we report the complete sequence of a 160,489 bp circular plasmid (pCBMA213_2) from an atypical and fast-growing environmental mycobacteria. This is a unique plasmid, in comparison with the characterised mycobacteria plasmids, harboring a type IV-like and ESX-P2 type VII secretion systems. pCBMA213_2 can be further explored for evolutionary and conjugation studies as well as a tool to manipulate DNA within this bacteria genus.
Vagal and sympathetic mechanisms in patients with orthostatic vasovagal syncope.

BACKGROUND Autonomic and particularly sympathetic mechanisms play a central role in the pathophysiology of vasovagal syncope. We report direct measurements of muscle sympathetic nerve activity in patients with orthostatic vasovagal syncope. METHODS AND RESULTS We studied 53 otherwise healthy patients with orthostatic syncope. We measured RR intervals and finger arterial pressures and in 15 patients, peroneal nerve muscle sympathetic activity before and during passive 60 degree head-up tilt, with low-dose intravenous isoproterenol if presyncope did not develop by 15 minutes. We measured baroreflex gain before tilt with regression of RR intervals or sympathetic bursts on systolic or diastolic pressures after sequential injections of nitroprusside and phenylephrine. Orthostatic vasovagal reactions occurred in 21 patients, including 7 microneurography patients. Presyncopal and nonsyncopal patients had similar baseline RR intervals, arterial pressure, and muscle sympathetic nerve activity. Vagal baroreflex responses were significantly impaired at arterial pressures below (but not above) baseline levels in presyncopal patients. Initial responses to tilt were comparable; however, during the final 200 seconds of tilt, presyncopal patients had lower RR intervals and diastolic pressures than nonsyncopal patients and gradual reduction of arterial pressure and sympathetic activity. Frank presyncope began abruptly with precipitous reduction of arterial pressure, disappearance of muscle sympathetic nerve activity, and RR interval lengthening. CONCLUSIONS Patients with orthostatic vasovagal reactions have impaired vagal baroreflex responses to arterial pressure changes below resting levels but normal initial responses to upright tilt. Subtle vasovagal physiology begins before overt presyncope. The final trigger of human orthostatic vasovagal reactions appears to be the abrupt disappearance of muscle sympathetic nerve activity.
Enterotoxigenic Escherichia coli Secretes a Highly Conserved Mucin-Degrading Metalloprotease To Effectively Engage Intestinal Epithelial Cells

ABSTRACT Enterotoxigenic Escherichia coli (ETEC) is a leading cause of death due to diarrheal illness among young children in developing countries, and there is currently no effective vaccine. Many elements of ETEC pathogenesis are still poorly defined. Here we demonstrate that YghJ, a secreted ETEC antigen identified in immunoproteomic studies using convalescent patient sera, is required for efficient access to small intestinal enterocytes and for the optimal delivery of heat-labile toxin (LT). Furthermore, YghJ is a highly conserved metalloprotease that influences intestinal colonization of ETEC by degrading the major mucins in the small intestine, MUC2 and MUC3. Genes encoding YghJ and its cognate type II secretion system (T2SS), which also secretes LT, are highly conserved in ETEC and exist in other enteric pathogens, including other diarrheagenic E. coli and Vibrio cholerae bacteria, suggesting that this mucin-degrading enzyme may represent a shared virulence feature of these important pathogens.
Complications of gallstone disease: mirizzi syndrome, cholecystocholedochal fistula, and gallstone ileus

Gallstone is a common disease with a 10% prevalence in the United States and Western Europe. However, it is only symptomatic in 20–30% of patients, with biliary pain “colic” being the most common symptom. Complications of asymptomatic gallstone disease are generally rare, with an incidence of <1%/yr. The most common complications of gallstone disease are acute cholecystitis, acute pancreatitis, ascending cholangitis, and gangrenous gallbladder. Less frequent complications include Mirizzi syndrome, cholecystocholedochal fistula, and gallstone ileus. Mirizzi syndrome and cholecystocholedochal fistula are two manifestations of the same process that starts with impaction of a gallstone in the gallbladder neck that results in obstruction of the bile duct, causing jaundice. The gallstone may erode into the bile duct, causing cholecystocholedochal fistula. Gallstone ileus refers to small bowel obstruction resulting from the impaction of one or more gallstones after they have migrated through a cholecystoenteric fistula. An accurate diagnosis is essential to the management and prevention of further complications. A variety of imaging and endoscopic modalities are used to make the diagnosis once the condition is suspected clinically. Treatment should be tailored to each individual patient. Management choices include ERCP, lithotripsy (endoscopic or extracorporeal), and surgery. Prognosis is frequently related to early recognition, management of any comorbid conditions, and careful selection of treatment modalities.
Co-expression of the collagen receptors leukocyte-associated immunoglobulin-like receptor-1 and glycoprotein VI on a subset of megakaryoblasts

Background The collagen receptor glycoprotein VI generates activating signals through an immunoreceptor tyrosine-based activating motif on the co-associated Fc receptor gamma chain. Leukocyte-associated immunoglobulin-like receptor-1 also ligates collagen but generates inhibitory signals through immunoreceptor tyrosine-based inhibitory motifs. Thus far, the cellular expression of glycoprotein VI and leukocyte-associated immunoglobulin-like receptor-1 appears mutually exclusive. Design and Methods Using flow cytometry, we studied expression of collagen receptors on differentiating human megakaryocytes. CD34+ cells were isolated from umbilical cord blood and matured to megakaryocytes in vitro. Freshly isolated bone marrow cells were used to study primary megakaryocytes. Upon cell sorting, cytospins were made to examine cytological characteristics of differentiation. Results Megakaryocyte maturation is accompanied by up-regulation of glycoprotein VI and down-regulation of leukocyte-associated immunoglobulin-like receptor-1. Interestingly, both in cultures from hematopoietic stem cells and primary cells obtained directly from bone marrow, we identified a subset of morphologically distinct megakaryocytes which co-express glycoprotein VI and leukocyte-associated immunoglobulin-like receptor-1. Conclusions This is the first report of a primary cell that co-expresses these collagen receptors with opposite signaling properties. Since megakaryocytes mature in the collagen-rich environment of the bone marrow, these findings may point to a role for leukocyte-associated immunoglobulin-like receptor-1 in the control of megakaryocyte maturation/migration.
Care Transitions: Integrating Transition Theory and Complexity Science Concepts

Care transitions, defined as hospital discharge or movement from one health care setting to another, are currently a major concern of health care providers and policy makers. Extensive empirical research has been conducted on care transitions, but the theoretical foundations are rarely made explicit. We propose that integrating concepts on complex adaptive systems from complexity science with classic theory on transitions in nursing provides a powerful new lens through which to study care transitions and improve transition outcomes. We summarize concepts from both theoretical approaches, propose an expanded model of transitions, and apply the model to the transition from hospital to home.
Ca2+ Binding to Troponin C in Skinned Skeletal Muscle Fibers Assessed with Caged Ca2+ and a Ca2+ Fluorophore

Ca2+ sensitivity of tension varies with sarcomere length in both skeletal and cardiac muscles. One possible explanation for this effect is that the Ca2+ affinity of the regulatory protein troponin C decreases when sarcomere length is reduced. To examine length dependence of Ca2+ binding to troponin C in skeletal muscle, we developed a protocol to simultaneously monitor changes in sarcomere length, tension, and Ca2+ concentration following flash photolysis of caged Ca2+. In this protocol, [Ca2+] was rapidly increased by flash photolysis of caged Ca2+, and changes in [Ca2+] due to photolysis and the subsequent binding to troponin C were assessed using a Ca2+ fluorophore. Small bundles of fibers from rabbit skinned psoas muscles were loaded with Ca2+ fluorophore (Fluo-3) and caged Ca2+ (dimethoxynitrophenamine or o-nitrophenyl-EGTA). The bundles were then transferred to silicone oil, where [Ca2+]free, tension, and sarcomere length were monitored before and after photolysis of caged Ca2+. Upon photolysis of caged Ca2+, fluorescence increased and then decayed to a new steady-state level within ∼1 s, while tension increased to a new steady-state level within ∼1.5 s. After extracting troponin C, fibers did not generate tension following the flash, but steady-state post-flash fluorescence was significantly greater than when troponin C was present. The difference in [Ca2+]free represents the amount of Ca2+ bound to troponin C. In fibers that were troponin C-replete, Ca2+ binding to troponin C did not differ at short (∼1.97 μm) and long (∼2.51 μm) sarcomere length, yet tension was ∼50% greater at the long sarcomere length. These results show that the affinity of troponin C for Ca2+ is not altered by changes in sarcomere length, indicating that length-dependent changes in Ca2+ sensitivity of tension in skeletal muscle are not related to length-dependent changes in Ca2+ binding affinity of troponin C.
CD8alpha(-) and CD8alpha(+) subclasses of dendritic cells undergo phenotypic and functional maturation in vitro and in vivo.

Dendritic cells (DCs) are essential for the priming of immune responses. This antigen-presenting function of DCs develops in sequence in a process called maturation, during which they become potent sensitizers of naïve T cells but reduce their ability to capture and process antigens. Some heterogeneity exists in mouse-DC populations, and two distinct subsets of DCs expressing high levels of CD11c can be identified on the basis of CD8alpha expression. We have studied the phenotype and maturation state of mouse splenic CD8alpha(-) and CD8alpha(+) DCs. Both subsets were found to reside in the spleen as immature cells and to undergo a phenotypic maturation upon culture in vitro in GM-CSF-containing medium or in vivo in response to lipopolysaccharide. In vitro and in vivo analyses showed that this maturation process is an absolute requisite for DCs to acquire their T-cell priming capacity, transforming CD8alpha(-) and CD8alpha(+) DCs into potent and equally efficient activators of naïve CD4(+) and CD8(+) T cells. Furthermore, these results highlight the importance that environmental factors may have on the ability of DC subsets to influence Th responses qualitatively; i.e., the ability to drive Th1 versus Th2 differentiation may not be fixed immutably for each DC subset.