Ultrasonic mapping of midpalatal suture - An ex-vivo study.

OBJECTIVE: Rapid maxillary expansion is a common orthodontic procedure to correct maxillary constriction. Assessing the midpalatal suture (MPS) expansion plays a crucial role in treatment planning to determine its effectiveness. The objectives of this preliminary investigation are to demonstrate a proof of concept that the palatal bone underlying the rugae can be clearly imaged by ultrasound (US) and the reconstructed axial view of the US image accurately maps the MPS patency. METHODS: An ex-vivo US scanning was conducted on the upper jawbones of two piglet's carcasses before and after the creation of bone defects, which simulated the suture opening. The planar images were processed to enhance bone intensity distribution before being orderly stacked to fuse into a volume. Graph-cut segmentation was applied to delineate the palatal bone to generate a bone volume. The accuracy of the reconstructed bone volume and the suture opening was validated by the micro-computed tomography (µCT) data used as the ground truth and compared with cone beam computed tomography (CBCT) data as the clinical standard. Also included in the comparison is the rugae thickness. Correlation and Bland-Altman plots were used to test the agreement between the two methods: US versus µCT/CBCT. RESULTS: The reconstruction of the US palatal bone volumes was accurate based on surface topography comparison with a mean error of 0.19 mm for pre-defect and 0.15 mm and 0.09 mm for post-defect models of the two samples, respectively when compared with µCT volumes. A strong correlation (R2 ≥ 0.99) in measuring MPS expansion was found between US and µCT/CBCT with MADs of less than 0.05 mm, 0.11 mm and 0.23 mm for US, µCT and CBCT, respectively. CONCLUSIONS: It was possible to axially image the MPS opening and rugae thickness accurately using high-frequency ultrasound. CLINICAL SIGNIFICANCE: This study introduces an ionizing radiation-free, low-cost, and portable technique to accurately image a difficult part of oral cavity anatomy. The advantages of conceivable visualization could promise a successful clinical examination of MPS to support the predictable treatment outcome of maxillary transverse deficiency.

Intermittent Kac's flights and the generalized telegrapher's equation.

A generalized one-dimensional telegrapher equation associated with an intermittent change of sign in the velocity of a Kac's flight has been proposed. To solve this random differential equation, we used the enlarged master equation approach to obtain the exact differential equation for the evolution of a normalized positive distribution. This distribution is associated with a generalized finite-velocity diffusionlike process. We studied the robustness of the ballistic regime, the cutoff of its domain, and the time-dependent Gaussian convergence. The second moment for the evolution of the profile has been studied as a function of non-Poisson statistics (possibly intermittent) for the time intervals Δ_{ij} in the Kac's flight. Numerical results for the evolution of sharp and wide initial profiles have also been presented. In addition, for comparison with a non-Gaussian process at all times, we have revisited the non-Markov Poisson's flight with exponential pulses. A theory for generalized random flights with intermittent stochastic velocity and in the presence of a force is also presented, and the stationary distribution for two classes of potential has been obtained.

Fisher and Shannon Functionals for Hyperbolic Diffusion.

The complexity measure for the distribution in space-time of a finite-velocity diffusion process is calculated. Numerical results are presented for the calculation of Fisher's information, Shannon's entropy, and the Cramér-Rao inequality, all of which are associated with a positively normalized solution to the telegrapher's equation. In the framework of hyperbolic diffusion, the non-local Fisher's information with the x-parameter is related to the local Fisher's information with the t-parameter. A perturbation theory is presented to calculate Shannon's entropy of the telegrapher's equation at long times, as well as a toy model to describe the system as an attenuated wave in the ballistic regime (short times).

Compensating transport trends in the Drake Passage frontal regions yield no acceleration in net transport.

Although the westerly winds that drive the Antarctic Circumpolar Current (ACC) have increased over the past several decades, the ACC response remains an open question. Here we use a 15-year time series of concurrent upper-ocean temperature, salinity, and ocean velocity with high spatial resolution across Drake Passage to analyze whether the net Drake Passage transport has accelerated in the last 15 years. We find that, although the net Drake Passage transport relative to 760 m shows insignificant acceleration, the net transport trend comprises compensating trends across the ACC frontal regions. Our results show an increase in the mesoscale eddy activity between the fronts consistent with buoyancy changes in the fronts and with an eddy saturation state. Furthermore, the increased eddy activity may play a role in redistributing momentum across the ACC frontal regions. The increase in eddy activity is expected to intensify the eddy-driven upwelling of deep warm waters around Antarctica, which has significant implications for ice-melting, sea level rise, and global climate.

Predictors of Willingness to Participate in COVID-19 Screening Testing from a Pilot School Survey in the United States.

BACKGROUND: COVID-19 screening testing (ST) can detect asymptomatic or pre-symptomatic cases, allowing for prompt identification of cases and close contacts. This study examined parents' and school staffs' knowledge and attitudes toward to a pilot school-based ST program in a school district in southern Arizona. METHODS: In May 2021, online surveys to parents and school staff were administered to examine attitudes toward ST and impacts of the COVID-19 pandemic. Unweighted percent estimates were calculated, and bivariate differences were examined by demographics. Associations were assessed using chi-square tests and logistic regression. RESULTS: The survey had response rates of 10% (606/6085) and 22% (187/849) among parents and staff, respectively. Approximately one-third of responding parents (35%) would or already allow their child to participate in school-based ST, 37% would not participate; 28% were unsure. Among responding staff, 46% would or already participate in ST, 33% would not; 21% were unsure. The top concern (38%) among responding staff was taking job-related leave if testing positive. CONCLUSION: Schools work to balance the needs of students, families, and staff by implementing supportive and flexible policies and practices founded on buy-in and acceptance from their communities.

New twists of a TAIL: novel insights into the histone binding properties of a highly conserved PHD finger cluster within the MLR family of H3K4 mono-methyltransferases.

Enhancer activation by the MLR family of H3K4 mono-methyltransferases requires proper recognition of histones for the deposition of the mono-methyl mark. MLR proteins contain two clusters of PHD zinc finger domains implicated in chromatin regulation. The second cluster is the most highly conserved, preserved as an ancient three finger functional unit throughout evolution. Studies of the isolated 3rd PHD finger within this cluster suggested specificity for the H4 [aa16-20] tail region. We determined the histone binding properties of the full three PHD finger cluster b module (PHDb) from the Drosophila Cmi protein which revealed unexpected recognition of an extended region of H3. Importantly, the zinc finger spacer separating the first two PHDb fingers from the third is critical for proper alignment and coordination among fingers for maximal histone engagement. Human homologs, MLL3 and MLL4, also show conservation of H3 binding, expanding current views of histone recognition for this class of proteins. We further implicate chromatin remodeling by the SWI/SNF complex as a possible mechanism for the accessibility of PHDb to globular regions of histone H3 beyond the tail region. Our results suggest a two-tail histone recognition mechanism by the conserved PHDb domain involving a flexible hinge to promote interdomain coordination.

Penetration of waves in global stochastic conducting media.

The attenuation in the propagation of a plane wave in conducting media has been studied. We analyzed a wave motion suffering dissipation by the Joule effect in its propagation in a medium with global disorder. We solved the stochastic telegrapher's equation in the Fourier-Laplace representation allowing us to find the space penetration length of a plane wave in a complex conducting medium. Considering fluctuations in the loss of energy, we found a critical value k_{c} for Fourier's modes, thus if |k|

Predictors for surgical site infection in patients undergoing therapeutic or prophylactic intra-abdominal onlay mesh (IPOM) implantation in clean and contaminated surgical fields.

BACKGROUND: Prophylactic intra-abdominal onlay mesh (IPOM) implantation has been shown to reduce the rate of fascial dehiscence and incisional hernia. However, surgical site infection (SSI) in presence of an IPOM remains a concern. The aim of this study was to assess predictors for SSI following IPOM placement in hernia and non-hernia abdominal surgery in clean and contaminated surgical fields. METHODS: Observational study including patients undergoing IPOM placement at a Swiss tertiary care hospital 2007-2016. IPOM implantation was performed in hernia and non-hernia elective and emergency abdominal surgery, including contaminated and infected surgical fields. The incidence of SSI was prospectively assessed by Swissnoso according to CDC criteria. The effect of disease- and procedure-related factors on SSI was assessed in multivariable regression analysis, adjusting for patient-related factors. RESULTS: A total of 1072 IPOM implantations were performed. Laparoscopy was performed in 415 patients (38.7%), laparotomy in 657 patients (61.3%). SSI occurred in 172 patients (16.0%). Superficial, deep, and organ space SSI were found in 77 (7.2%), 26 (2.4%), and 69 (6.4%) patients, respectively. Multivariable analysis revealed emergency hospitalization (OR 1.787, p = 0.006), previous laparotomy (1.745, p = 0.029), duration of operation (OR 1.193, p < 0.001), laparotomy (OR 6.167, p < 0.001), bariatric (OR 4.641, p < 0.001), colorectal (OR 1.941, p = 0.001), and emergency (OR 2.510, p < 0.001) surgery, wound class ≥ 3 (OR 3.878, p < 0.001), and non-polypropylene mesh (OR 1.818, p = 0.003) as independent predictors for SSI. Hernia surgery was independently associated with a lower risk for SSI (OR 0.165, p < 0.001). CONCLUSION: This study revealed emergency hospitalization, previous laparotomy, duration of operation, laparotomy, as well as bariatric, colorectal, and emergency surgery, abdominal contamination or infection, and usage of non-polypropylene mesh as independent predictors for SSI. In contrast, hernia surgery was associated with a lower risk for SSI. The knowledge of these predictors will help to balance benefits of IPOM implantation against the risk for SSI.

ILC2 require cell-intrinsic ST2 signals to promote type 2 immune responses.

The initiation of type 2 immune responses at mucosal barriers is regulated by rapidly secreted cytokines called alarmins. The alarmins IL-33, IL-25 and TSLP are mainly secreted by stromal and epithelial cells in tissues and were linked to chronic inflammatory diseases, such as allergic lung inflammation, or to resistance against worm infections. Receptors for alarmins are expressed by a variety of immune cells, including group 2 innate lymphoid cells (ILC2s), an early source of the type 2 cytokines, such as IL-5 and IL-13, which have been linked to atopic diseases and anti-worm immunity as well. However, the precise contribution of the IL-33 receptor signals for ILC2 activation still needs to be completed due to limitations in targeting genes in ILC2. Using the newly established Nmur1 iCre-eGFP mouse model, we obtained specific conditional genetic ablation of the IL-33 receptor subunit ST2 in ILC2s. ST2-deficient ILC2s were unresponsive to IL-33 but not to stimulation with the alarmin IL-25. As a result of defective ST2 signals, ILC2s produced limited amounts of IL-5 and IL-13 and failed to support eosinophil homeostasis. Further, ST2-deficient ILC2s were unable to expand and promote the recruitment of eosinophils during allergic lung inflammation provoked by papain administration. During infection with Nippostrongylus brasiliensis, ILC2-intrinsic ST2 signals were required to mount an effective type 2 immune response against the parasite leading to higher susceptibility against worm infection in conditional knockout mice. Therefore, this study argues for a non-redundant role of cell-intrinsic ST2 signals triggering proper activation of ILC2 for initiation of type 2 immunity.

Development and initial validation of a questionnaire to measure patient experience with oral appliance therapy.

STUDY OBJECTIVES: To develop and validate a questionnaire to measure patient experience with oral appliance therapy. METHODS: The AMEE Guide No. 87 was followed in the development and validation of a patient questionnaire to assess patient experience with oral appliance therapy. RESULTS: Our search identified 522 articles; 5 of these articles described the use and/or validation of questionnaires to measure changes in symptoms and patient-reported outcomes in the treatment of obstructive sleep apnea. A total of 27 questions were developed. Five patients participated in pilot testing. A final review of the questionnaire was conducted by an expert panel. CONCLUSIONS: The creation and validation of a questionnaire to assess patient experience with oral appliance therapy may provide new methods for advancing research in the field of dental sleep medicine. CITATION: Ng ET, Perez-Garcia A, Lagravère-Vich MO. Development and initial validation of a questionnaire to measure patient experience with oral appliance therapy. J Clin Sleep Med. 2023;19(8):1437-1445.

RNA binding induces an allosteric switch in Cyp33 to repress MLL1-mediated transcription.

Mixed-lineage leukemia 1 (MLL1) is a transcription activator of the HOX family, which binds to specific epigenetic marks on histone H3 through its third plant homeodomain (PHD3) domain. Through an unknown mechanism, MLL1 activity is repressed by cyclophilin 33 (Cyp33), which binds to MLL1 PHD3. We determined solution structures of Cyp33 RNA recognition motif (RRM) free, bound to RNA, to MLL1 PHD3, and to both MLL1 and the histone H3 lysine N6-trimethylated. We found that a conserved α helix, amino-terminal to the RRM domain, adopts three different positions facilitating a cascade of binding events. These conformational changes are triggered by Cyp33 RNA binding and ultimately lead to MLL1 release from the histone mark. Together, our mechanistic findings rationalize how Cyp33 binding to MLL1 can switch chromatin to a transcriptional repressive state triggered by RNA binding as a negative feedback loop.

ILC3s restrict the dissemination of intestinal bacteria to safeguard liver regeneration after surgery.

It is generally believed that environmental or cutaneous bacteria are the main origin of surgical infections. Therefore, measures to prevent postoperative infections focus on optimizing hygiene and improving asepsis and antisepsis. In a large cohort of patients with infections following major surgery, we identified that the causative bacteria are mainly of intestinal origin. Postoperative infections of intestinal origin were also found in mice undergoing partial hepatectomy. CCR6+ group 3 innate lymphoid cells (ILC3s) limited systemic bacterial spread. Such bulwark function against host invasion required the production of interleukin-22 (IL-22), which controlled the expression of antimicrobial peptides in hepatocytes, thereby limiting bacterial spread. Using genetic loss-of-function experiments and punctual depletion of ILCs, we demonstrate that the failure to restrict intestinal commensals by ILC3s results in impaired liver regeneration. Our data emphasize the importance of endogenous intestinal bacteria as a source for postoperative infection and indicate ILC3s as potential new targets.

Cardiometabolic risk factors and antithrombotic treatment in a Mexican population with atrial fibrillation and heart failure with reduced ejection fraction.

INTRODUCTION: Heart failure in patients with non-valvular atrial fibrillation (NVAF) is two to three times more common than in individuals without NVAF. OBJECTIVE: To identify cardiometabolic risk factors (CMRF) and antithrombotic treatment in patients with NVAF and heart failure with reduced ejection fraction (HFrEF), and to determine if there were differences according to gender. METHODS: CMRF, pro-thrombotic risk, bleeding risk, and antithrombotic therapy were globally analyzed and according to gender. RESULTS: Out of 1,423 patients with NVAF, 336 had HFrEF. On average, females were older than males. There was no difference between genders with regard to the type of NVAF or direct oral anticoagulants use. Hypertension was more common in women. History of transient ischemic attack was reported in 3.6% of the patients and cerebrovascular event in 10%, without differences in terms of gender. The percentage of men with elevated embolic risk was higher, but without antithrombotic treatment, in comparison with women. CONCLUSIONS: Significant differences were found according to gender in patients with NVAF and HFrEF, both in CMRF and some comorbidities, as well as in antithrombotic treatment according to embolic and bleeding risk.

INTRODUCCIÓN: La insuficiencia cardiaca en pacientes con fibrilación auricular no valvular (FANV) es de dos a tres veces más frecuente que en individuos sin FANV. OBJETIVO: Identificar los factores de riesgo cardiometabólico (FRCM) y el tratamiento antitrombótico de pacientes con FANV e insuficiencia cardiaca con fracción de expulsión reducida (IC-FEr), y determinar si existen diferencias conforme al sexo. MÉTODOS: En forma global y de acuerdo con el sexo se analizaron FRCM, riesgo protrombótico, riesgo de sangrado y terapia antitrombótica. RESULTADOS: De 1423 pacientes con FANV, 336 tuvieron IC-FEr. Las mujeres promediaron mayor edad que los hombres. No hubo diferencia entre los sexos respecto al tipo de FANV o uso de anticoagulantes orales directos. La hipertensión arterial sistémica fue más frecuente en mujeres. Un 3.6 % de los pacientes reportó antecedente de ataque isquémico transitorio y 10 % de evento vascular cerebral, sin diferencias en cuanto al sexo. El porcentaje de hombres con riesgo embólico elevado fue mayor, pero sin tratamiento antitrombótico, en comparación con las mujeres. CONCLUSIONES: Se encontraron diferencias significativas de acuerdo con el sexo en pacientes con FANV e IC-FEr, tanto en FRCM y algunas comorbilidades, como en el tratamiento antitrombótico de acuerdo con el riesgo embólico y de sangrado.

Factores de riesgo cardiometabólico y tratamiento antitrombótico en población mexicana con fibrilación auricular e insuficiencia cardiaca con fracción de expulsión reducida / Cardiometabolic risk factors and antithrombotic treatment in a Mexican population with atrial fibrillation and heart failure with reduced ejection fraction

Resumen Introducción: La insuficiencia cardiaca en pacientes con fibrilación auricular no valvular (FANV) es de dos a tres veces más frecuente que en individuos sin FANV. Objetivo: Identificar los factores de riesgo cardiometabólico (FRCM) y el tratamiento antitrombótico de pacientes con FANV e insuficiencia cardiaca con fracción de expulsión reducida (IC-FEr), y determinar si existen diferencias conforme al sexo. Métodos: En forma global y de acuerdo con el sexo se analizaron FRCM, riesgo protrombótico, riesgo de sangrado y terapia antitrombótica. Resultados: De 1423 pacientes con FANV, 336 tuvieron IC-FEr. Las mujeres promediaron mayor edad que los hombres. No hubo diferencia entre los sexos respecto al tipo de FANV o uso de anticoagulantes orales directos. La hipertensión arterial sistémica fue más frecuente en mujeres. Un 3.6 % de los pacientes reportó antecedente de ataque isquémico transitorio y 10 % de evento vascular cerebral, sin diferencias en cuanto al sexo. El porcentaje de hombres con riesgo embólico elevado fue mayor, pero sin tratamiento antitrombótico, en comparación con las mujeres. Conclusiones: Se encontraron diferencias significativas de acuerdo con el sexo en pacientes con FANV e IC-FEr, tanto en FRCM y algunas comorbilidades, como en el tratamiento antitrombótico de acuerdo con el riesgo embólico y de sangrado.

Abstract Introduction: Heart failure in patients with non-valvular atrial fibrillation (NVAF) is two to three times more common than in individuals without NVAF. Objective: To identify cardiometabolic risk factors (CMRF) and antithrombotic treatment in patients with NVAF and heart failure with reduced ejection fraction (HFrEF), and to determine if there were differences according to gender. Methods: CMRF, pro-thrombotic risk, bleeding risk, and antithrombotic therapy were globally analyzed and according to gender. Results: Out of 1,423 patients with NVAF, 336 had HFrEF. On average, females were older than males. There was no difference between genders with regard to the type of NVAF or direct oral anticoagulants use. Hypertension was more common in women. History of transient ischemic attack was reported in 3.6% of the patients and cerebrovascular event in 10%, without differences in terms of gender. The percentage of men with elevated embolic risk was higher, but without antithrombotic treatment, in comparison with women. Conclusions: Significant differences were found according to gender in patients with NVAF and HFrEF, both in CMRF and some comorbidities, as well as in antithrombotic treatment according to embolic and bleeding risk.

Non-redundant functions of group 2 innate lymphoid cells.

Protective immunity relies on the interplay of innate and adaptive immune cells with complementary and redundant functions. Innate lymphoid cells (ILCs) have recently emerged as tissue-resident, innate mirror images of the T cell system, with which they share lineage-specifying transcription factors and effector machinery1. Located at barrier surfaces, ILCs are among the first responders against invading pathogens and thus could potentially determine the outcome of the immune response2. However, so far it has not been possible to dissect the unique contributions of ILCs to protective immunity owing to limitations in specific targeting of ILC subsets. Thus, all of the available data have been generated either in mice lacking the adaptive immune system or with tools that also affect other immune cell subsets. In addition, it has been proposed that ILCs might be dispensable for a proper immune response because other immune cells could compensate for their absence3-7. Here we report the generation of a mouse model based on the neuromedin U receptor 1 (Nmur1) promoter as a driver for simultaneous expression of Cre recombinase and green fluorescent protein, which enables gene targeting in group 2 ILCs (ILC2s) without affecting other innate and adaptive immune cells. Using Cre-mediated gene deletion of Id2 and Gata3 in Nmur1-expressing cells, we generated mice with a selective and specific deficiency in ILC2s. ILC2-deficient mice have decreased eosinophil counts at steady state and are unable to recruit eosinophils to the airways in models of allergic asthma. Further, ILC2-deficient mice do not mount an appropriate immune and epithelial type 2 response, resulting in a profound defect in worm expulsion and a non-protective type 3 immune response. In total, our data establish non-redundant functions for ILC2s in the presence of adaptive immune cells at steady state and during disease and argue for a multilayered organization of the immune system on the basis of a spatiotemporal division of labour.

Fibrilación auricular en población mexicana: Diferencias en presentación, comorbilidades y factores de riesgo entre hombres y mujeres / Atrial fibrillation in Mexican population: Differences in presentation, comorbidities and risk factors between men and women

Resumen Objetivo: Conocer el comportamiento epidemiológico y asociaciones de la FA en población mexicana. Material y métodos: Analizamos 8,686 pacientes de 38 cardiólogos inscritos en REMECAR, divididos por edad y sexo. Comorbilidades estudiadas: obesidad, ERC, HTA, DM, dislipidemia, EVC, EPOC, hipotiroidismo, IC y CI. Programa: IBM SPSS. Resultados: FA en 498 pacientes (5.7%), mayor prevalencia en hombres (6.1 vs. 5.3%), mayor edad en mujeres (74.3 ± 12.1 vs. 70.5 ± 12.3 años, p < 0.0001). En mujeres menores de 60 años la FA se asoció con IC (p = 0.041), en hombres con ERC (p = 0.43), DM (p = 0.009), EVC (p = 0.001), hipotiroidismo (p = 0.001) e IC (p = 0.001). En mujeres mayores de 60 años se asoció con ERC (p = 0.001), dislipidemia (p = 0.001), EVC (p = 0.001), EPOC (p = 0.001) e IC (p = 0.001), en hombres con ERC (p = 0.002), EVC (p = 0.001), EPOC (p = 0.002), hipotiroidismo (p = 0.002), IC (p = 0.001) y CI (p = 0.033). En mujeres la FA se asoció con 1.13 veces mayor probabilidad de obesidad, 1.13 de HTA, 2.8 de ERC, 2.9 de EPOC, 4.3 de EVC y 6.5 de IC, en hombres la FA se asoció con 1.05 veces mas probabilidad de HTA, 1.4 de DM, 2.1 de ERC, 2.4 de EPOC, 3 de hipotiroidismo, 4.7 de EVC y 6 de IC. Conclusiones: La FA es una arritmia muy frecuente, con mayor prevalencia en pacientes que acuden a consulta de cardiología, en hombres y mayor edad de presentación en las mujeres. A mayor edad, mayor prevalencia de FA y de comorbilidades, la IC es la condición más frecuente con la que se asoció la FA.

Abstract Objective: To know the epidemiological behavior and associations of AF in Mexican population. Material and methods: 8,686 patients from 38 cardiologists participating in REMECAR were analyzed. They were divided by gender and age, the comorbidities studied were obesity, chronic kidney disease (CKD), high blood pressure (HBP), diabetes mellitus (DM), dyslipidemia, stroke, chronic obstructive pulmonary disease (COPD), hypothyroidism, heart failure (HF) and ischemic heart disease (IHD). Program used: IBM SPSS Statistic. Results: AF was diagnosed in 498 patients (5.7%), with higher prevalence in men (6.1% vs. 5.3%) and older age in women (74.3 ± 12.1 vs. 70.5 + -12.3 years, p<0.0001). In those under 60 years, AF was associated in women with HF, in men with CKD, DM, stroke, hypothyroidism and HF. In women older than 60 years, AF was associated with CKD, dyslipidemia, stroke, chronic COPD and HF, in men with CKD, stroke, COPD, hypothyroidism, HF and IHD. AF in women increase the probability 1.13 for obesity, 1.13 for HBP, 2.8 for CKD, 2.9 for COPD, 4.3 for stroke and 6.5 for HF, in men increase the probability 1.05 for HBP, 1.4 for DM, 2.1 for CKD, 2.4 for COPD, 3.0 for hypothyroidism, 4.7 for stroke and 6.0 for HF. Conclusions: AF is a very common arrhythmia, with a higher prevalence in patients attending the cardiology consultation, in men and with an older age of presentation in women. The older the age, the higher the prevalence of AF and comorbidities, HF is the most frequent condition associated with AF.

Hepatic blood flow regulation but not oxygen extraction capability is impaired in prolonged experimental abdominal sepsis.

Impaired oxygen utilization has been proposed to play a significant role in sepsis-induced liver dysfunction, but its magnitude and temporal course during prolonged resuscitation is controversial. The aim of this study is to evaluate the capability of the liver to increase oxygen extraction in sepsis during repeated acute portal vein blood flow reduction. Twenty anesthetized and mechanically ventilated pigs with hepatic hemodynamic monitoring were randomized to fecal peritonitis or controls (n = 10, each). After 8-h untreated sepsis, the animals were resuscitated for three days. The ability to increase hepatic O2 extraction was evaluated by repeated, acute decreases in hepatic oxygen delivery (Do2) via reduction of portal flow. Blood samples for liver function and liver biopsies were obtained repeatedly. Although liver function tests, ATP content, and Do2 remained unaltered, there were signs of liver injury in blood samples and overt liver cell necrosis in biopsies. With acute portal vein occlusion, hepatic Do2 decreased more in septic animals compared with controls [max. decrease: 1.66 ± 0.68 mL/min/kg in sepsis vs. 1.19 ± 0.42 mL/min/kg in controls; portal venous flow (Qpv) reduction-sepsis interaction: P = 0.028]. Hepatic arterial buffer response (HABR) was impaired but recovered after 3-day resuscitation, whereas hepatic oxygen extraction increased similarly during the procedures in both groups (max. increase: 0.27 ± 0.13 in sepsis vs. 0.18 ± 0.09 in controls; all P > 0.05). Our data indicate maintained capacity of the liver to acutely increase O2 extraction, whereas blood flow regulation is transiently impaired with the potential to contribute to liver injury in sepsis.NEW & NOTEWORTHY The capacity to acutely increase hepatic O2 extraction with portal flow reduction is maintained in sepsis with accompanying liver injury, but hepatic blood flow regulation is impaired.

Surgical site infections after simultaneous pancreas kidney and pancreas transplantation in the Swiss Transplant Cohort Study.

BACKGROUND: Among hospital-acquired infections, surgical site infections (SSIs) are frequent. SSI in the early post-transplant course poses a relevant threat to transplant recipients. AIM: To determine incidence, risk factors for SSI and its association with post-transplant outcomes and pancreas transplant (P-Tx) recipients. METHODS: Adult simultaneous kidney-pancreas transplantation (SPK-T) and P-Tx recipients with a follow-up of at least 90 days were identified in the Swiss Transplant Cohort Study (STCS) dataset. Except for the categorization of SSIs according to Centers for Disease Control and Prevention (CDC) criteria, all other data were prospectively collected. Risk factors for SSI were investigated with logistic regression. A Weibull accelerated failure-time model was applied to address the impact of SSI on length of stay, correcting for transplant-related complications and delayed graft function. FINDINGS: Of 130 transplant recipients, 108 SPK-Tx and 22 P-Tx, 18 (14%) individuals developed SSI within the first 90 days after transplantation. Deep incisional (seven, 38.9%) and organ/space infections (eight, 44.4%) predominated. In the majority of SSIs (11, 61.1%; two SSIs with simultaneous identification of fungal pathogens) bacteria were detected with Enterococcus spp. being most frequent. The median duration of hospitalization after transplantation was significantly longer in recipients with SSI (median: 26 days; interquartile range (IQR): 19-44) than in patients without SSI (median: 17 days; IQR: 12-25; P = 0.002). In multivariate analysis, SSI was significantly associated with increased length of stay and prolonged the duration of hospitalization by 36% (95% confidence interval: 4-79). CONCLUSION: SSI after SPK-Tx and P-Tx occurred at a frequency of 14%. Among pathogens, Enterococcus spp. predominated. SSI was independently associated with a longer hospitalization after transplantation.

The ctpF Gene Encoding a Calcium P-Type ATPase of the Plasma Membrane Contributes to Full Virulence of Mycobacterium tuberculosis.

Identification of alternative attenuation targets of Mycobacterium tuberculosis (Mtb) is pivotal for designing new candidates for live attenuated anti-tuberculosis (TB) vaccines. In this context, the CtpF P-type ATPase of Mtb is an interesting target; specifically, this plasma membrane enzyme is involved in calcium transporting and response to oxidative stress. We found that a mutant of MtbH37Rv lacking ctpF expression (MtbΔctpF) displayed impaired proliferation in mouse alveolar macrophages (MH-S) during in vitro infection. Further, the levels of tumor necrosis factor and interferon-gamma in MH-S cells infected with MtbΔctpF were similar to those of cells infected with the parental strain, suggesting preservation of the immunogenic capacity. In addition, BALB/c mice infected with Mtb∆ctpF showed median survival times of 84 days, while mice infected with MtbH37Rv survived 59 days, suggesting reduced virulence of the mutant strain. Interestingly, the expression levels of ctpF in a mouse model of latent TB were significantly higher than in a mouse model of progressive TB, indicating that ctpF is involved in Mtb persistence in the dormancy state. Finally, the possibility of complementary mechanisms that counteract deficiencies in Ca2+ transport mediated by P-type ATPases is suggested. Altogether, our results demonstrate that CtpF could be a potential target for Mtb attenuation.

Stochastic telegrapher's approach for solving the random Boltzmann-Lorentz gas.

The 1D random Boltzmann-Lorentz equation has been connected with a set of stochastic hyperbolic equations. Therefore, the study of the Boltzmann-Lorentz gas with disordered scattering centers has been transformed into the analysis of a set of stochastic telegrapher's equations. For global binary disorder (Markovian and non-Markovian) exact analytical results for the second moment, the velocity autocorrelation function, and the self-diffusion coefficient are presented. We have demonstrated that time-fluctuations in the lost of energy in the telegrapher's equation, can delay the entrance to the diffusive regime, this issue has been characterized by a timescale t_{c} which is a function of disorder parameters. Indeed, producing a longer ballistic dynamics in the transport process. In addition, fluctuations of the space probability distribution have been studied, showing that the mean value of a stochastic telegrapher's Fourier mode is a good statistical object to characterize the solution of the random Boltzmann-Lorentz gas. In a different context, the stochastic telegrapher's equation has also been related to the run-and-tumble model in Biophysics. Then a discussion devoted to the potential applications when swimmers' speed and tumbling rate have time fluctuations has been pointed out.