Miracle-dz/UniFAR-FTUs huggingface dataset:
Catheter steering in interventional cardiology: Mechanical analysis and novel solution

In recent years, steerable catheters have been developed to combat the effects of the dynamic cardiac environment. Mechanically actuated steerable catheters appear the most in the clinical setting; however, they are bound to a number of mechanical limitations. The aim of this research is to gain insight in these limitations and use this information to develop a new prototype of a catheter with increased steerability. The main limitations in mechanically steerable catheters are identified and analysed, after which requirements and solutions are defined to design a multi-steerable catheter. Finally, a prototype is built and a proof-of-concept test is carried out to analyse the steering functions. The mechanical analysis results in the identification of five limitations: (1) low torsion, (2) shaft shortening, (3) high unpredictable friction, (4) coupled tip-shaft movements, and (5) complex cardiac environment. Solutions are found to each of the limitations and result in the design of a novel multi-steerable catheter with four degrees of freedom. A prototype is developed which allows the dual-segmented tip to be steered over multiple planes and in multiple directions, allowing a range of complex motions including S-shaped curves and circular movements. A detailed analysis of limitations underlying mechanically steerable catheters has led to a new design for a multi-steerable catheter for complex cardiac interventions. The four integrated degrees of freedom provide a high variability of tip directions, and repetition of the bending angle is relatively simple and reliable. The ability to steer inside the heart with a variety of complex shaped curves may potentially change conventional approaches in interventional cardiology towards more patient-specific and lower complexity procedures. Future directions are headed towards further design optimizations and the experimental validation of the prototype.
Early Enteral Nutrition Is Associated With Improved Clinical Outcomes in Critically Ill Children: A Secondary Analysis of Nutrition Support in the Heart and Lung Failure-Pediatric Insulin Titration Trial

Supplemental Digital Content is available in the text. Objectives: The impact of early enteral nutrition on clinical outcomes in critically ill children has not been adequately described. We hypothesized that early enteral nutrition is associated with improved clinical outcomes in critically ill children. Design: Secondary analysis of the Heart and Lung Failure-Pediatric Insulin Titration randomized controlled trial. Setting: Thirty-five PICUs. Patients: Critically ill children with hyperglycemia requiring inotropic support and/or invasive mechanical ventilation who were enrolled for at least 48 hours with complete nutrition data. Interventions: Subjects received nutrition via guidelines that emphasized enteral nutrition and were classified into early enteral nutrition (enteral nutrition within 48 hr of study randomization) and no early enteral nutrition (enteral nutrition after 48 hr of study randomization, or no enteral nutrition at any time). Measurements and Main Results: Of 608 eligible subjects, 331 (54%) received early enteral nutrition. Both early enteral nutrition and no early enteral nutrition groups had similar daily caloric intake over the first 8 study days (median, 36 vs 36 kcal/kg/d; p = 0.93). After controlling for age, body mass index z scores, primary reason for ICU admission, severity of illness, and mean Vasopressor-Inotrope Score at the time of randomization, and adjusting for site, early enteral nutrition was associated with lower 90-day hospital mortality (8% vs 17%; p = 0.007), more ICU-free days (median, 20 vs 17 d; p = 0.02), more hospital-free days (median, 8 vs 0 d; p = 0.003), more ventilator-free days (median, 21 vs 19 d; p = 0.003), and less organ dysfunction (median maximum Pediatric Logistic Organ Dysfunction, 11 vs 12; p < 0.001). Conclusions: In critically ill children with hyperglycemia requiring inotropic support and/or mechanical ventilation, early enteral nutrition was independently associated with better clinical outcomes.
Topical Adjuvant Application during Subcutaneous Vaccination Promotes Resident Memory T Cell Generation

Key Points Topical CpG adjuvant with s.c. Ag vaccination promotes skin CD8 TRM. Topical CpG adjuvant activity depends on TLR9 expression by hematopoietic cells. Topical CpG adjuvant promotes global protection against dermal tumor challenge. Skin tissue resident memory T cells (TRM) provide superior protection to a second infection. In this study, we evaluated the use of topical CpG oligodeoxynucleotide (ODN) as adjuvant to generate skin TRM in mice. Topical or s.c. CpG ODN adjuvant administration at the time of a s.c. Ag injection led to an accumulation of CD103− CD8 T cells in the epidermis. However, only mice with CpG ODN administered topically had significant numbers of CD103+ Ag-specific CD8 T cells persisting in the local epidermal skin, enhanced circulating memory cells in the blood, and showed protection from intradermal challenge with melanoma cells. Generation of Ag-specific CD8 T cells was dependent on TLR9 expression on hematopoietic cells and partially dependent on receptor expression on stromal cells. Topical challenge of immunized mice at a distal site led to significant expansion of Ag-specific T cells in the blood and accumulation in the challenged skin. We demonstrate that local and systemic T cell memory can be generated with topical CpG ODN at the time of s.c. immunization, suggesting a new method of enhancing current vaccine formulations to generate tissue TRM.
Mariticide in Milan between 1990 and 2017: A criminological and medico-legal analysis

Most murder victims in a romantic relationship are women but sometimes they will kill their husbands or partners (mariticide). This paper focuses on these rarer cases using a sample taken from the autopsy reports of the Department of Legal Medicine of the University of Milan whose territory includes the municipality of Milan and part of the province of Milan and Monza – approximately four million inhabitants.
Identification of a novel X-linked arginine-vasopressin receptor 2 mutation in nephrogenic diabetes insipidus

Abstract Introduction: The clinical and genetic characteristics of nephrogenic diabetes insipidus (NDI) were described via assessing 2 cases of NDI patients from a Chinese family. Patient concerns: Two patients who manifest polyuria and polydipsia were admitted to hospital for definite diagnosis. Diagnosis: Water deprivation-vasopressin tests showed that the patients may possess renal-origin diabetes insipidus. All the levels of thyroid-stimulating hormone, luteinizing hormone, follicle stimulation hormone, adrenocorticotropic hormone, prolactin, and growth hormone in both patients were normal. These results were certified that both patients possess a nephropathy-type diabetes insipidus. B-mode ultrasonography and urinalysis test demonstrated that the patient's diabetes insipidus is unlikely to originate from renal organic disease. Remarkably, by nucleotide sequencing, we found a novel mutation c. 414_418del in arginine-vasopressin receptor 2 (AVPR2) was related to the disease of NDI. Interventions: Two patients were treated with oral hydrochlorothiazide and indomethacin. In addition, low salt diet and potassium supplementation throughout the patients’ treatment. Outcomes: The clinical symptoms of 2 patients were significantly reduced after targeted therapy. Conclusion: A mutation in AVPR2 was discovered to be associated with NID. It provides a new target for molecular diagnosis of NDI, enabling families to undergo genetic counseling and obtain prenatal diagnoses.
Evaluation of MRI and CT parameters to analyze the correlation between disc and facet joint degeneration in the lumbar three-joint complex

Abstract Lumbar 3-joint complex degeneration is a multifactorial, pathological process. Previous studies included insufficient quantitative analyses to prove the relationship between disc degeneration and facet joint osteoarthritis (OA). We assessed the correlation between intervertebral disc and lumbar facet joint degeneration using computed tomography (CT) and magnetic resonance imaging (MRI) parameters. A total of 152 participants who underwent conventional MRI and CT in the clinostat position were included in this study. The presence of lumbar disc degeneration was identified using the Pfirrmann grading system, and the presence of lumbar facet joint degeneration was identified using the Weishaupt grading system. Facet tropism was defined as a divergence more than 7° between the facet joint angles of both sides at the same segment. The intervertebral disc heights were also measured. Most facet joint OA probably appeared at the segment with intervertebral disc degeneration of more than grade III. Facet joint OA was significantly exacerbated with the progression of disc degeneration grade. The intervertebral height significantly decreased with the progression of facet joint degeneration grades, except for grades 0 and 1. Our current study found that each individual joint degeneration influences the other 2 in the lumbar 3-joint complex. Facet tropism was significantly associated with lumbar disc degeneration. Narrowing of the intervertebral disc height probably aggravates the facet joint degeneration further at the same level.
AAV2‐BDNF promotes respiratory axon plasticity and recovery of diaphragm function following spinal cord injury

More than half of spinal cord injury (SCI) cases occur in the cervical region, leading to respiratory dysfunction due to damaged neural circuitry that controls critically important muscles such as the diaphragm. The C3‐C5 spinal cord is the location of phrenic motor neurons (PhMNs) that are responsible for diaphragm activation; PhMNs receive bulbospinal excitatory drive predominately from supraspinal neurons of the rostral ventral respiratory group (rVRG). Cervical SCI results in rVRG axon damage, PhMN denervation, and consequent partial‐to‐complete paralysis of hemidiaphragm. In a rat model of C2 hemisection SCI, we expressed the axon guidance molecule, brain‐derived neurotrophic factor (BDNF), selectively at the location of PhMNs (ipsilateral to lesion) to promote directed growth of rVRG axons toward PhMN targets by performing intraspinal injections of adeno‐associated virus serotype 2 (AAV2)‐BDNF vector. AAV2‐BDNF promoted significant functional diaphragm recovery, as assessed by in vivo electromyography. Within the PhMN pool ipsilateral to injury, AAV2‐BDNF robustly increased sprouting of both spared contralateral‐originating rVRG axons and serotonergic fibers. Furthermore, AAV2‐BDNF significantly increased numbers of putative monosynaptic connections between PhMNs and these sprouting rVRG and serotonergic axons. These findings show that targeting circuit plasticity mechanisms involving the enhancement of synaptic inputs from spared axon populations is a powerful strategy for restoring respiratory function post‐SCI.—Charsar, B. A. , Brinton, M. A. , Locke, K. , Chen, A. Y. , Ghosh, B. , Urban, M. W. , Komaravolu, S. , Krishnamurthy, K. , Smit, R. , Pasinelli, P., Wright, M. C. , Smith, G. M. , Lepore, A. C. AAV2‐BDNF promotes respiratory axon plasticity and recovery of diaphragm function following spinal cord injury. FASEB J. 33, 13775‐13793 (2019). www.fasebj. org
Modification of the mechanical cardiac performance during end-expiratory voluntary apnea recorded with ballistocardiography and seismocardiography

Objective: To assess if micro-accelerometers and gyroscopes may provide useful information for the detection of breathing disturbances in further studies. Approach: Forty-three healthy volunteers performed a 10 s end-expiratory breath-hold, while ballistocardiograph (BCG) and seismocardiograph (SCG) determined changes in kinetic energy and its integral over time (iK, J · s). BCG measures overall body accelerations in response to blood mass ejection into the main vasculature at each cardiac cycle, while SCG records local chest wall vibrations generated beat-by-beat by myocardial activity. This minimally intrusive technology assesses linear accelerations and angular velocities in 12 degrees of freedom to calculate iK during the whole cardiac cycle. iK produced during systole and diastole were also computed. Main results: The iK during normal breathing was 87.1 [63.3; 132.8] µJ · s for the SCG and 4.5 [3.3; 6.2] µJ · s for the BCG. Both increased to 107.1 [69.0; 162.0] µJ · s and 6.1 [4.4; 9.0] µJ · s, respectively, during breath-holding (p = 0.003 and p < 0.0001, respectively). The iK of the SCG further increased during spontaneous respiration following apnea (from 107.1 [69.0; 162.0] µJ · s to 160.0 [96.3; 207.3] µJ · s, p < 0.0001). The ratio between the iK of diastole and systole increased from 0.35 [0.24; 0.45] during apnea to 0.49 [0.31; 0.80] (p < 0.0001) during the restoration of respiration. Significance: A brief voluntary apnea generates large and distinct increases in SCG and BCG waveforms. iK monitoring during sleep may prove useful for the detection of respiratory disturbances. ClinicalTrials.gov number: NCT03760159
Investigation of the linear node movement patterns in wireless networks

MANETs are mobile, self-configuring networks of wireless mobile devices without an infrastructure. The operation of a MANET is affected by movement of the nodes. Because of the movement MANETs need to rely on robust routing protocols. We focus our investigation on the impact of movement patterns on operation of a MANET. Of particular interest are linear movement patterns similar to those observed in some man-made objects. We investigate the operation of a MANET under four different linear movement patterns by simulating a MANET running AODV routing protocol. The best results were obtained with nodes moving perpendicularly to the geographical direction of packet forwarding.
The use of platelet-rich plasma in oral surgery: a systematic review and meta-analysis.

BACKGROUND The aim of this systematic review and meta-analysis was to evaluate the benefit of platelet rich plasma (PRP) in oral surgery. MATERIALS AND METHODS We performed a systematic search of the literature. The GRADE system was used to assess the certainty of the body of evidence. RESULTS We found 21 randomised controlled trials that met our inclusion criteria: 12 studies included patients with periodontal defects, five studies focused on healing of extraction sockets, three studies on sinus lift augmentation, and one study on periapical osseous defects. However, for the quantitative synthesis (meta-analysis), we evaluated "periodontal defects" studies only, since for other clinical contexts the number of studies were too low and the procedural heterogeneity was too high to allow pooling of data. PRP-containing regimens were compared to non-PRP-containing regimens. Primary outcomes for the evaluation of periodontal defects were probing depths, clinical attachment level, gingival recession, and radiographic bone defect. It is not usually clear whether or not the use of PRP compared to controls affects "probing depth" at long-term follow up; the between group differences were small and unlikely to be of clinical importance (i.e., very low quality of evidence). For the other outcomes analysed ("clinical attachment levels", "gingival recession", "bony defect"), we observed a very slight marginal clinical benefit of PRP compared to controls. The available evidence for these comparisons was rated as low quality as most of the studies selected showed inconsistency, imprecision, and risk of bias. DISCUSSION Evidence from a comparison between the use in oral surgery of PRP-containing regimens compared to other regimens not-containing PRP was of low quality. The results of the meta-analysis, limited to studies in patients with periodontal defects, document that PRP was slightly more effective compared to controls not-containing PRP.
Selective-cold output via a distinct subset of lamina I spinoparabrachial neurons.

Spinal projection neurons are a major pathway through which somatic stimuli are conveyed to the brain. However, the manner in which this information is coded is poorly understood. Here, we report the identification of a modality-selective spinoparabrachial (SPB) neuron subtype with unique properties. Specifically, we find that cold-selective SPB neurons are differentiated by selective afferent input, reduced sensitivity to substance P, distinct physiological properties, small soma size, and low basal drive. In addition, optogenetic experiments reveal that cold-selective SPB neurons do not receive input from Nos1 inhibitory interneurons and, compared to other SPB neurons, show significantly smaller IPSCs upon activation of Pdyn inhibitory interneurons. Together, these data suggest that cold output from the spinal cord to the parabrachial nucleus is mediated by a specific cell type with distinct properties.
Impact of a community-based intervention on Latino grandparents' knowledge about and self-efficacy in supporting grandchildren's physical activities.

INTRODUCTION Latino grandparents are often involved in rearing grandchildren, but their roles in promoting children's physical activity (PA) have been largely overlooked. This study examined the impact of a community-based intervention called Nietos Activos y Saludables (Active and Healthy Grandchildren) on Latino grandparents' knowledge about and self-efficacy in supporting grandchildren's (aged 2-12 years) PA. METHOD The Spanish language intervention, consisting of 4 weekly sessions, was delivered to 12 Latino grandparents (primarily female, aged > 60 years) in Los Angeles County from October to November 2017. Pre- and posttest surveys and postintervention focus groups assessed the intervention impact. RESULTS Participants indicated that the intervention provided useful information. After intervention sessions, participants achieved a higher score in test on PA requirements for children. They also reported greater knowledge about children's PA, local resources for children's PA, and modifying children's behavior. Additionally, participants reported greater confidence in motivating children in PA and collaborating with parents in promoting children's PA. Results of focus groups generally confirmed the quantitative findings. DISCUSSION Nietos Activos y Saludables intervention has the promise to increase Latino grandparents' knowledge about and self-efficacy in supporting grandchildren's PA. Future studies should test the impact of the intervention on grandparents' behavior and grandchildren's health outcomes using a randomized controlled trial. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Dilated cardiomyopathy mutation in the converter domain of human cardiac myosin alters motor activity and response to omecamtiv mecarbil

We investigated a dilated cardiomyopathy (DCM) mutation (F764L) in human β-cardiac myosin by determining its motor properties in the presence and absence of the heart failure drug omecamtive mecarbil (OM). The mutation is located in the converter domain, a key region of communication between the catalytic motor and lever arm in myosins, and is nearby but not directly in the OM-binding site. We expressed and purified human β-cardiac myosin subfragment 1 (M2β-S1) containing the F764L mutation, and compared it to WT with in vitro motility as well as steady-state and transient kinetics measurements. In the absence of OM we demonstrate that the F764L mutation does not significantly change maximum actin-activated ATPase activity but slows actin sliding velocity (15%) and the actomyosin ADP release rate constant (25%). The transient kinetic analysis without OM demonstrates that F764L has a similar duty ratio as WT in unloaded conditions. OM is known to enhance force generation in cardiac muscle while it inhibits the myosin power stroke and enhances actin-attachment duration. We found that OM has a reduced impact on F764L ATPase and sliding velocity compared with WT. Specifically, the EC50 for OM induced inhibition of in vitro motility was 3-fold weaker in F764L. Also, OM reduces maximum actin-activated ATPase 2-fold in F764L, compared with 4-fold with WT. Overall, our results suggest that F764L attenuates the impact of OM on actin-attachment duration and/or the power stroke. Our work highlights the importance of mutation-specific considerations when pursuing small molecule therapies for cardiomyopathies.
Tissue engineering of retina through high resolution 3-dimensional inkjet bioprinting

The mammalian retina contains multiple cellular layers, each carrying out a specific task. Such a controlled organization should be considered as a crucial factor for designing retinal therapies. The maintenance of retinal layered complexity through the use of scaffold-free techniques has recently emerged as a promising approach for clinical ocular tissue engineering. In an attempt to fabricate such layered retinal model, we are proposing herein a unique inkjet bioprinting system applied to the deposition of a photoreceptor cells (PRs) layer on top of a bioprinted retinal pigment epithelium (RPE), in a precise arrangement and without any carrier material. The results showed that, after bioprinting, both RPE and PRs were well positioned in a layered structure and expressed their structural markers, which was further demonstrated by ZO1, MITF, rhodopsin, opsin B, opsin R/G and PNA immunostaining, three days after bioprinting. We also showed that considerable amounts of human vascular endothelial growth factors (hVEGF) were released from the RPE printed layer, which confirmed the formation of a functional RPE monolayer after bioprinting. Microstructures of bioprinted cells as well as phagocytosis of photoreceptor outer segments by apical RPE microvilli were finally established through transmission electron microscopy (TEM) imaging. In summary, using this carrier-free bioprinting method, it was possible to develop a reasonable in vitro retina model for studying some sight-threatening diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP).
Mapping of Shigella flexneri’s tissue distribution and type III secretion apparatus activity during infection of the large intestine of guinea pigs

ABSTRACT Shigella spp. are bacterial pathogens that invade the human colonic mucosa using a type III secretion apparatus (T3SA), a proteinaceous device activated upon contact with host cells. Active T3SAs translocate proteins that carve the intracellular niche of Shigella spp. Nevertheless, the activation state of the T3SA has not been addressed in vivo. Here, we used a green fluorescent protein transcription-based secretion activity reporter (TSAR) to provide a spatio-temporal description of S. flexneri T3SAs activity in the colon of Guinea pigs. First, we observed that early mucus release is triggered in the vicinity of luminal bacteria with inactive T3SA. Subsequent mucosal invasion showed bacteria with active T3SA associated with the brush border, eventually penetrating into epithelial cells. From 2 to 8 h post-challenge, the infection foci expanded, and these intracellular bacteria displayed homogeneously high-secreting activity, while extracellular foci within the lamina propria featured bacteria with low secretion activity. We also found evidence that within lamina propria macrophages, bacteria reside in vacuoles instead of accessing the cytosol. Finally, bacteria were cleared from tissues between 8 and 24 h post-challenge, highlighting the hit-and-run colonization strategy of Shigella. This study demonstrates how genetically encoded reporters can contribute to deciphering pathogenesis in vivo.