Degree Of Tissue Damage Research Articles

Identification and complete genome of lytic “Kp34likevirus” phage vB_KpnP_Bp5 and therapeutic potency in the treatment of lethal Klebsiella pneumoniae infections in mice

Klebsiella pneumoniae (K. pneumoniae) infection exist widely in the farming and medical. The treatment of K. pneumoniae infection is primarily based on antibiotics, which not only leads to a large economic burden but also the development of antibiotic resistance. Bacteriophages therapy present a promising alternative. The object of this study was identifying comprehensively a lytic lethal K. pneumoniae phage vB_KpnP_Bp5, and evaluating the phage as an anti-infective agent in an experimental K. pneumoniae infection murine model. The phage Bp5 had the following characteristics: the optimal number of infections was 0.001, the latent period was 5 min, the outbreak period was 40 min, the burst size was 24 plaque-forming unit (PFU)/cell, the phage could withstand 50 °C temperature and the optimal pH value was 4.0–10.0. According to electron microscopy and whole-genome sequence analysis, the phage should be classified as a member of order Caudovirales, family Podoviridae, subfamily Autographiviridae. Meantime, phylogenetic analysis showed high conservation of gene arrangement and gene content. We demonstrated that administration of phage Bp5 significantly reduced colony formation by K. pneumoniae and alleviated damage to lung tissue. In addition, different therapy time point was closely related to body health and the degree of tissue damage. Once treated promptly, it will greatly reduce mortality and alveolar inflammatory exudation and injury.

Mechanism of hypertensive crisis during energy device ablation of the adrenal gland: An experimental animal study.

To elucidate the mechanism of hypertensive crisis during energy device ablation of the adrenal gland. Electrocoagulation on the adrenal glands of six pigs was carried out with the same energy device (VIO300D) using four methods: (i) monopolar coagulation; (ii) monopolar soft coagulation using IO-advanced ball-type electrodes; (iii) bipolar soft coagulation by pinching; and (iv) bipolar soft coagulation by non-pinching (surface contact) using Bipolar forceps Premium. After electrocoagulation for 5s, blood pressure and pulse changes were monitored, and adrenal hormones were measured from a central vein. The adrenal glands were removed, and the degree of tissue damage was scored histologically. Hypertensive crisis occurred with electrocoagulation of the adrenal gland by the monopolar coagulation, monopolar soft coagulation and bipolar soft coagulation pinching methods. Blood pressure did not change with the bipolar soft coagulation non-pinching method. Pathologically, tissue damage to the adrenal medulla was associated with elevated blood pressure and adrenaline and noradrenaline release. Hypertensive crisis caused by energy device ablation to the adrenal gland is caused by the release of catecholamines due to heat damage to the adrenal medulla rather than the type of energy device. Proper use of an energy device that does not cause thermal degeneration of the medulla is required to prevent hypertensive crisis.

Ocular adverse events associated with immune checkpoint inhibitors: a novel multidisciplinary management algorithm.

Ocular immune-related adverse events (IrAEs) associated with use of checkpoint inhibitors (CPIs) in cancer therapeutics are relatively rare, occurring in approximately 1% of treated patients. Recognition and early intervention are essential because the degree of tissue damage may be disproportionate to the symptoms, and lack of appropriate treatment risks permanent loss of vision. International guidelines on managing ocular IrAEs provide limited advice only. Importantly, local interventions can be effective and may avoid the need for systemic corticosteroids, thereby permitting the continuation of CPIs. We present a single institution case series of eight affected patients managed by our multidisciplinary team. Consistent with previously published series and case reports, we identified anterior uveitis as the most common ocular IrAE associated with CPIs requiring intervention. Based on our experience, as well as published guidance, we generated a simple algorithm to assist clinicians efficiently manage patients developing ocular symptoms during treatment with CPIs. In addition, we make recommendations for optimising treatment of uveitis and address implications for ongoing CPI therapy.

The Use of Low Intensity Laser in Wound Healing in Dog

Background: Low-intensity laser is effective in cellular metabolism, analgesia, and tissue repair. The bioelectric, bioenergetic, and biochemical effects of laser therapy stimulate local circulation, collagen formation, and epithelization. The objective of this study was to report the use of gallium-aluminum arsenide (GaAlAs) laser (830 nm) in healing two wounds caused by necrosis in a dog.Case: An 8-year-old bitch, a rescued victim of animal abuse, had tibiotarsal dislocation in the left posterior limb. Orthopedic surgery was performed with the placement of an external fixation device with six pins in the distal third of the left posterior limb. A radiographic examination performed 42 days after the surgery revealed the loss of the tibiotarsal ratio, decreased radiopacity of the carpal bones, edema, inflammation, muscle atrophy, and the rotation of the anatomical axis of the metatarsals and phalanges. It was then decided to perform a second orthopedic surgery, in which a bone graft and arthrodesis with an 8-screw titanium plate were performed. Four of the plate screws were placed proximally to the tibia and four distally to the tarsus in addition to a screw and a pin transfixed through the distal metaphyseal region of the tibia and calcaneus. Traction was felt during suturing in the dermis and epidermis of the limb, suggesting the possibility of dehiscence of the stitches. After 3 h of surgery, the limb was cold and edematous. After 5 days, the tissue of the medial region of the tarsus developed necrosis, exposing a wound 6 cm long, 1.5 cm wide, and 2 mm deep (wound 1). Another necrotic lesion was observed in the dorsal region of the tarsos - 6.5 cm long, 2 cm wide, 3 mm deep, and exposing 5 cm of the titanium plate (wound 2). Therapy with GaAlAs laser was then performed over the entire length of the wounds. In each therapeutic session, the laser was first used in punctual mode at 10 J/cm², 830 nm, 20 s at each point of the length of the lesion and then in scan mode at 10 J/cm², 830 nm, 1000 Hz, and 40 s continuously. Laser therapy sessions were conducted at 2-4 day intervals, with a 12-day interval between the eighth and ninth sessions. During the entire treatment, cleansing and debridement of the wounds were performed every 48 h with saline and chlorhexidine digluconate, using a compression bandage, as described earlier. Wound 1 healed completely after two laser therapy sessions. In wound 2, tissue repair stagnated after the ninth and last laser session, leaving 4 cm of the titanium plate still exposed. The limb could not support the body weight of the patient, and radiographic examination revealed that the anatomical axis of the metatarsals and the phalanges was rotated and bone conformation was poor. Given the anatomical conditions associated with the patient's clinical picture, it was decided to amputate the limb between the femur and tibia.Discussion: Therapeutic lasers act on mitochondrial respiration, increasing respiratory metabolism and stimulating DNA synthesis and tissue proliferation. In the present case, there was a decrease in inflammatory cells, edema, and the size of the wounds. The pathological conditions of the affected site, influence of trauma, and degree of tissue damage affected the results of the laser therapy. Despite the size difference between wounds 1 and 2, the exposed titanium plate was a determining factor for the partial healing of wound 2. Keywords: laser, laser therapy, scar, necrosis, orthopedics, physical therapy, tissue repair. Título: A utilização do laser de baixa intensidade na cicatrização de ferida em cão.Descritores: laser, laserterapia, cicatriz, necrose, ortopedia, fisioterapia, reparo tecidual.

Interventions for frostbite injuries.

Frostbite is a thermal injury caused when tissue is exposed to sub-zero temperatures (in degrees Celsius) long enough for ice crystals to form in the affected tissue. Depending on the degree of tissue damage, thrombosis, ischaemia, necrosis (tissue death), gangrene and ultimately amputation may occur. Several interventions for frostbite injuries have been proposed, such as hyperbaric oxygen therapy, sympathectomy (nerve block), thrombolytic (blood-thinning) therapy and vasodilating agents such as iloprost, reserpine, pentoxifylline and buflomedil, but the benefits and harms of these interventions are unclear. To assess the benefits and harms of the different management options for frostbite injuries. On 25 February 2020, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase (OvidSP), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), Conference Proceedings Citation Index-Science (CPCI-S), as well as trials registers. Shortly before publication, we searched Clinicaltrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform, OpenGrey and GreyLit (9 November 2020) again. We investigated references from relevant articles, and corresponded with a trial author. We included randomised controlled trials (RCTs) that compared any medical intervention, e.g. pharmacological therapy, topical treatments or rewarming techniques, for frostbite injuries to another treatment, placebo or no treatment. Two authors independently extracted data. We used Review Manager 5 for statistical analysis of dichotomous data with risk ratio (RR) with 95% confidence intervals (CIs). We used the Cochrane 'Risk of bias' tool to assess bias in the included trial. We assessed incidence of amputations, rates of serious and non-serious adverse events, acute pain, chronic pain, ability to perform activities of daily living, quality of life, withdrawal rate from medical therapy due to adverse events, occupational effects and mortality. We used GRADE to assess the quality of the evidence. We included one, open-label randomised trial involving 47 participants with severe frostbite injuries. We judged this trial to be at high risk of bias for performance bias, and uncertain risk for attrition bias; all other risk of bias domains we judged as low. All participants underwent rapid rewarming, received 250 mg of aspirin and 400 mg intravascular (IV) buflomedil (since withdrawn from practice), and were then randomised to one of three treatment groups for the following eight days. Group 1 received additional IV buflomedil 400 mg for one hour per day. Group 2 received the prostacyclin, iloprost, 0.5 ng to 2 ng/kg/min IV for six hours per day. Group 3 received IV iloprost 2 ng/kg/min for six hours per day plus fibrinolysis with 100 mg recombinant tissue plasminogen activator (rtPA) for the first day only. The results suggest that iloprost and iloprost plus rtPA may reduce the rate of amputations in people with severe frostbite compared to buflomedil alone, RR 0.05 (95% CI 0.00 to 0.78; P = 0.03; very low-quality evidence) and RR 0.31 (95% CI 0.10 to 0.94; P = 0.04; very low-quality evidence), respectively. Iloprost may be as effective as iloprost plus rtPA at reducing the amputation rate, RR 0.14 (95% CI 0.01 to 2.56; P = 0.19; very low-quality evidence). There were no reported deaths or withdrawals due to adverse events in any of the groups; we assessed evidence for both outcomes as being of very low quality. Adverse events (including flushing, nausea, palpitations and vomiting) were common, but not reported separately by comparator arm (very low-quality evidence). The included study did not measure the outcomes of acute pain, chronic pain, ability to perform activities of daily living, quality of life or occupational effects. There is a paucity of evidence regarding interventions for frostbite injuries. Very low-quality evidence from a single small trial indicates that iloprost, and iloprost plus rtPA, in combination with buflomedil may reduce the need for amputation in people with severe frostbite compared to buflomedil alone. However, buflomedil has been withdrawn from use. High quality randomised trials are needed to establish firm evidence for the treatment of frostbite injuries.

Dexmedetomidine promotes the recovery of renal function and reduces the inflammatory level in renal ischemia-reperfusion injury rats through PI3K/Akt/HIF-1α signaling pathway.

To evaluate the protective effect of dexmedetomidine (Dex) against renal ischemia-reperfusion injury (RIRI) in rats through the phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (Akt)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway. (1) A Sprague- Dawley rat model of RIRI was established. Thirty rats were divided into Sham group, injury (RIRI) group, and Dex treatment (RIRI + Dex) group. Serum was collected to detect renal function-related indexes, and the levels of serum inflammatory factors were examined via enzyme-linked immunosorbent assay (ELISA). (2) The kidney tissues were separated, and the degree of tissue damage was determined using immunohistochemical staining. (3) Ribonucleic acids (RNAs) were extracted from tissues, and the mRNA levels of inflammatory factors were measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). (4) The protein expressions of Akt, phosphorylated (p)-Akt, PI3K, p-PI3K, and HIF-1α were detected via Western blotting. Compared with those in RIRI group, the levels of blood urea nitrogen and creatinine declined (p<0.05), the synthesized mRNAs of inflammatory factors in the kidney tissues were reduced (p<0.05), the secreted serum inflammatory factors was also reduced (p<0.05), and the phosphorylation levels of Akt and PI3K and the HIF-1α level rose (p<0.05) in RIRI + Dex group. Dex promotes the recovery of renal function and reduces the inflammatory level in RIRI rats through the PI3K/Akt/HIF-1α signaling pathway.

Chemotactic invasion in deep soft tissue by Vibrio vulnificus is essential for the progression of necrotic lesions

ABSTRACT Necrotizing soft tissue infections (NSTI) progress to severe necrosis and result in fatal sepsis within a short time. Vibrio vulnificus is a causative agent and can spread from the initial infection site through soft tissue finally to the systemic circulation of the host. The motility and chemotaxis of this bacterium are essential for proliferation and lethality in a murine model of the infection, but their role in pathogenicity has not been characterized. In this study, we revealed the roles of motility and chemotaxis during the process of V. vulnificus infection. We compared a nonmotile mutant and two nonchemotactic mutants with their parent strain (WT) with regard to bacterial spread using an in vivo imaging system (IVIS) and invasion by detection of bacteria from the muscle and spleen of a murine infection model. WT rapidly spread throughout the infected thigh and invaded deep muscle causing severe tissue damage. The detection rate in the systemic circulation and the lethality were high. On the other hand, the nonmotile mutant stayed at the inoculation site, and the nonchemotactic mutants spread only slowly through the soft tissue of the infected thigh. Detection in the systemic circulation, the degree of tissue damage, and the lethality of nonchemotactic mutants were significantly reduced in mice compared with WT. This study demonstrated that chemotaxis is essential for invasion from the infection site to the deep and distant tissues and the main pathogenic factor for the rapid progression leading to sepsis in V. vulnificus NSTI.

Relationship between Volume of Leukoaraiosis Spot and Degree of Tissue Damage: A Quantitative Diffusion Tensor Imaging Study

Diffusion tensor imaging (DTI) offers parameter indices, namely, mean diffusivity (MD) and fractional anisotropy (FA). Leukoaraiosis is a brain white matter hyperintensity as observed on fluid-attenuated inversion recovery (FLAIR) images. In this study, we attempt to assess leukoaraiosis at its specific spot using a new parameter, namely, lesion-to-normal appearing white matter ratio (LNR). LNR was then used to investigate the relationship between the volume of leukoaraiosis spot and the degree of tissue damage. This study involved 49 leukoaraiosis subjects who altogether contributed to 274 leukoaraiosis spots. The MD, FA, and volume were measured at each spot. LNR was calculated by comparing the MD values of the spot with those of the surrounding normal-appearing white matter (NAWM). The correlation between MD, FA, and LNR with leukoaraiosis volume was then analysed. The leukoaraiosis tissues generally exhibited higher MD (103.97 ± 12.32 × 10-5 mm2/s) and lower FA (0.31 ± 0.08) values than the NAWM tissues (79.30 ± 4.76 × 10-5 mm2/s and 0.41 ± 0.09, respectively). LNR values were found to range from 0.04 to 1.63. The results showed an insignificant association between the leukoaraiosis volume and LNR [r = −.055, p = .368], whereas a very weak association was shown with MD [r = −.196,p =.001] and FA [r = .268, p < .001]. The volume of the leukoaraiosis spot does not necessarily indicate the degree of tissue damage. By using LNR instead of MD, an accurate analysis was performed since the variability of MD for NAWM surrounding the lesion is taken into account.

ОЦЕНКА ИСХОДНОГО СТАТУСА ПАЦИЕНТОВ С ПОЛИТРАВМОЙ КАК ОСНОВНОЙ КОМПОНЕНТ СТРАТЕГИИ АНАЛГОСЕДАЦИИ ПАЦИЕНТОВ В ОИТ

Известно, что хирургическое вмешательство вызывает воспалительную реакцию, величина которой зависит от типа операции и степени повреждения ткани [2]. Эта послеоперационная воспалительная реакция сопровождается депрессией клеточного иммунитета, что в свою очередь предрасполагает пациентов к послеоперационным инфекциям и сепсису. Еще одной проблемой, выявленной нами, является то, что оценка влияния препаратов в ОИТ начинается как бы «с чистого листа», без учета уже имеющихся изменений в соматическом, иммунном и гормональном состояниях, связанных как с самим фактом травмы, так и с фактом оперативного вмешательства и уже имеющимся влиянием препаратов для общей анестезии на пациентов с политравмой. Цель исследования. Определить исходный статус пациентов с политравмой при поступлении в ОИТ для разработки превентивной стратегии аналгоседации, что выполняется впервые.Материал и методы. В исследовании участвовали 78 пациентов с политравмой, находящихся в ОИТ, из которых 62,8% составили мужчины и 37,2% – женщины. Средний возраст всех пациентов – 52,2±3,5 года. Сбор анамнеза и жалоб пациентов включал в себя оценку по шкалам SOFA, GCS, MRS, MMSE. Оценивались уровни белка S-100 и цилиарный нейротрофический фактор (CNTF).Результаты и обсуждение. Оценив по шкале SOFA, мы установили, что лишь 30% пациентов с политравмой требуют перевода в ОИТ с длительной ИВЛ и аналгоседацией. Эти пациенты пребывают в состоянии выраженного иммунодефицита и требуют комплексного подхода к лечению. Заключение. Пациентам на длительной ИВЛ необходимо тщательно подбирать стратегию аналгоседации с учетом исходного состояния и биоритмологических особенностей. Необходимо тщательно подбирать режимы ИВЛ, следить за оксигенацией. Немаловажным этапом лечения является подбор нутритивной поддержки с наиболее ранним переходом на энтеральное питание. Заключительным этапом является индивидуальный подбор антибиотикотерапии для предотвращения осложнений ИВЛ.

Enrichment of Antigen-Specific Class-Switched B Cells from Individuals Naturally Immunized by Infection with Group A Streptococcus.

The low frequency of circulating antigen-specific memory B cells is a considerable obstacle in the discovery and development of human monoclonal antibodies for therapeutic application. Here, we evaluate two solid-phase isolation methods to enrich the number of antigen-specific B cells from individuals naturally immunized against streptolysin O (SLO), a key virulence factor and known immunogen of group A streptococcus (GAS). Class-switched B cells obtained from individuals with a history of GAS infection were separated from peripheral blood mononuclear cells (PBMCs) by immunomagnetic methods. SLO-specific B cells were further enriched directly by binding to SLO monomers and captured by streptavidin-coated magnetic microbeads or indirectly by binding a fluorescently labeled SLO-streptavidin tetramer and captured by anti-fluorophore immunomagnetic microbeads. SLO-bound B cells were quantitated by flow cytometry and/or expanded in batch culture to determine IgG specificity. From individuals who have suffered a GAS infection ≥2 years prior, only the direct method enriched SLO-specific B cells, as determined by flow cytometry. Likewise, in batch culture, B cells isolated by the direct method resulted in an average of 375-fold enrichment in anti-SLO IgG, while no enrichment was observed for B cells isolated by the indirect method. The direct method established here provides a simple approach to increase low-frequency antigen-specific B cell populations supporting many downstream applications, such as immortalization of B cells, cloning of immunoglobulin genes, or purification of antibodies from supernatant for future study. Overall, this process is efficient, is inexpensive, and can be applied to many naturally immunogenic antigens.IMPORTANCE Bacteria called group A streptococci can cause a variety of skin and soft tissue infections ranging from mild pharyngitis ("strep throat") to deadly necrotizing fasciitis (sometimes called "flesh-eating" disease). In each case, the development of disease and the degree of tissue damage are mediated by toxins released from the bacteria during infection. Consequently, novel therapies aimed at clearing bacterial toxins are greatly needed. One promising new treatment is the utilization of monoclonal antibodies delivered as an immunotherapeutic for toxin neutralization. However, current methods of antibody development are laborious and costly. Here, we report a method to enrich and increase the detection of highly desirable antigen-specific memory B cells from individuals previously exposed to GAS using a cost-effective and less-time-intensive strategy. We envision that this method will be incorporated into many applications supporting the development of immunotherapeutics.

The effects of hydrogen-rich saline solution on intestinal anastomosis performed after intestinal ischemia reperfusion injury

AimWe investigated the effects of hydrogen-rich saline solution (HRSS) on intestinal anastomosis performed after intestinal ischemia reperfusion injury (IRI). Materials and methodsThirty Wistar albino female rats were randomly divided into five groups. Only laparotomy was performed in the Sham group. In the other four groups, an intestinal IRI was performed for 45 min by clamping the superior mesenteric artery. After intestinal IRI, anastomosis was performed by cutting the intestine from the proximal 15 cm of the ileocecal valve at the first and 24th hours. HRSS was given intraperitoneally 5 ml/kg before reperfusion and for four more days in the HRSS1 and HRSS24groups, while no treatment was given to the I/R1 and I/R24 groups. After 5 days, all groups underwent relaparotomy. The anastomotic bursting pressures were measured in all groups, except the Sham group. The tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), myeloperoxidase (MPO) and malondialdehyde (MDA) levels were measured in the tissues taken from the anastomosis line. The tissue sections were evaluated histopathologically and the apoptosis index was determined by applying the TUNEL method. The results were analyzed one-way analysis of variance (ANOVA) and Pearson's chi-squared test. ResultsAlthough the MPO, MDA, IL-6 and TNF-α tissue values were not statistically significant among the groups, the degree of tissue damage and apoptosis levels were lower and the anastomotic bursting pressures values were higher in the HRSS1 and HRSS24 groups compared to the I/R1 and I/R24 groups. ConclusionHRSS is effective in reducing the intestinal damage caused by an IRI: HRSS has the potential to reduce the detrimental effects of intestinal anastomosis performed after an intestinal IRI.

Trends in Demographics and Surgical Treatment of Weapon-Related Limb Injuries Over Two Decades in a Resource-Scarce Setting

BackgroundIn the past decades, surgical management of limb injuries in high-resource settings has improved. The possibility of limb salvage has increased. It is not known whether similar changes have transpired in resource-scarce conflict settings.MethodsRetrospective cohort study using routinely collected patient data from the International Committee of the Red Cross hospitals in Pakistan was conducted. Consecutive data from 2009 to 2012 (535 patients) and randomly selected data from 1992 to 1995 (463 patients) were used. Only patients with weapon-related limb injuries were included. Differences in surgical procedures were assessed with logistic regression to adjust for confounding factors.ResultsLess injuries were related to mines in 2009–2012 than in 1992–1995 (3.7% vs. 20.3%, p < 0.0001), but injuries from bombs, shells and fragments were more frequent (38.5% vs. 19.4%, p < 0.0001) as were injuries with only a small degree of tissue damage (42.0% vs. 31.1%, p = 0.0004). In the logistic regression, the time period did not affect the risk of amputation, debridement, length of hospital stay or in-hospital mortality. The use of external fixation (OR 0.56, 95% CI 0.33–0.96, p = 0.04), split skin grafts (OR 0.31, 95% CI 0.21–0.45, p < 0.0001) and blood transfusion (OR 0.43, 95% CI 0.28–0.66, p = 0.0001) was less frequent in 2009–2012.ConclusionIn this resource-scarce conflict setting, the risk of amputation appears unchanged over time, while the use of external fixation and split skin grafts was less common in 2009–2012 than in 1992–1995. These results contrast with the improved limb salvage results seen in high-resource settings. It likely reflects the challenges of providing advanced limb-preserving techniques in a resource-scarce setting.

Differences in Morphometric Measures of the Uninjured Porcine Spinal Cord and Dural Sac Predict Histological and Behavioral Outcomes after Traumatic Spinal Cord Injury.

One of the challenges associated with conducting experiments in animal models of traumatic spinal cord injury (SCI) is inducing a consistent injury with minimal variability in the degree of tissue damage and resultant behavioral and biochemical outcomes. We evaluated how the variability in morphometry of the spinal cord and surrounding cerebrospinal fluid (CSF) contributes to the variability in behavioral and histological outcomes in our porcine model of SCI. Using intraoperative ultrasound imaging, spinal cord morphometry was assessed in seven Yucatan minipigs undergoing a weight-drop T10 contusion-compression injury. Bivariate and multi-variate analysis and modeling were used to identify native morphometrical determinants of interanimal variability in histological and behavioral outcomes. The measured biomechanical impact parameters did not correlate with the histological measures or hindlimb locomotor behavior (Porcine Thoracic Injury Behavior Scale). In contrast, clear associations were revealed between CSF layer morphometry and the amount of white matter and tissue sparing. Specifically, the dorsoventral diameter of the dural sac and ventral CSF space were strong predictors of behavioral and histological outcome and together explained ≥95.0% of the variance in these parameters. In addition, a dorsoventral diameter of the spinal cord less than 5.331 mm was a strong contributing factor to poor behavioral recovery over 12 weeks. These results indicate that interanimal variability in cord morphometry provides a potential biological explanation for the observed heterogeneity in histological and behavioral outcomes. Such knowledge is helpful for appropriately balancing experimental groups, and/or varying impact parameters to match cord and CSF layer dimensions for future studies.

Proteasome Activity and C-Reactive Protein Concentration in the Course of Inflammatory Reaction in Relation to the Type of Abdominal Operation and the Surgical Technique Used.

Surgical tissue damage and the accompanying inflammatory response lead to proteasome activation, initiation of damaged protein degradation, and induction of acute-phase inflammatory response. The aim of this study was to investigate the rate of change in proteasome chymotrypsin-like (ChT-L) activity and C-reactive protein concentration depending on the degree of tissue damage and their correlation with prealbumin concentrations in children before and after abdominal surgery. This experimental study included children who underwent abdominal surgery between 2015 and 2017. Plasma prealbumin concentrations and C-reactive protein levels (CRP) were determined by standard biochemical laboratory procedures. Proteasome activity was assessed using a Suc-Leu-Leu-Val-Tyr-AMC peptide substrate. Elevation of plasma proteasome activity was noted in children after laparoscopic and open abdominal surgeries. However, 20S proteasome activity in children undergoing conventional open surgery was significantly higher (P < 0.05) than in patients subjected to laparoscopy. At the same time, an increase in the CRP level was observed. However, there was no correlation between C-reactive protein concentrations and the type of abdominal surgery while there was a correlation observed in the case of proteasomes. Proteasome activity correlates with the degree of surgical tissue damage and prealbumin concentrations. More invasive surgery leads to a stronger activation of the proteasome involved in removing proteins that were damaged due to the surgical procedure. Proteasomes are more specific markers because there is a correlation between proteasome activity and the type of abdominal surgery in contrast to C-reactive protein concentrations which are not different in response to surgery performed in regard to ovarian cysts or cholelithiasis.

The therapeutic effect of Yinhuangerchen mixture on Avian infectious laryngotracheitis.

The study was conducted to investigate the effect of Yinhuangerchen mixture (YM) on Avian infectious laryngotracheitis (AILT) induced by artificial infection and provide a scientific basis for its clinical application. A total of 200 chickens were challenged with infectious laryngotracheitis virus (ILTV). At 72 h post-challenge, the chickens were treated with different doses of YM or the Chinese herbal medicine Houyanjing powder. The relative expression of ILTV, the pathological changes of trachea, and the number of SIgA-secreting cells were detected. Thin-layer chromatography results confirmed that the YM contained Scutellaria baicalensis, Flos lonicerae, Pericarpium citri reticulatae, and Liquorice. The AILT model was successfully established by artificial infection. In the high-dose YM group (HD) and middle-dose YM group (MD), the effective rate of treatment was 100 and 96.7%, respectively, and the overall cure rate was 83.3%. In addition, the results of necropsy showed that the degree of tissue damage in chicken trachea was relatively low. Compared with positive control group, HD and MD chicken had lower relative expression of ILTV but more SIgA-secreting cells. In conclusion, YM can reduce ILTV level in tissue, mitigate tissue damage caused by infection, and enhance mucosal immunity having obvious therapeutic effect on AILT.

Histotripsy—From nucleation of bubbles to tissue disruption

Histotripsy utilizes focused ultrasound to nucleate gas bubbles deep within tissue and the associated bubble activity to induce biological effects at the level of tissue disruption/emulsification. Ultrasonic fields for inducing such effects include both pulses with as little as a single predominant negative half cycle to pulses with thousands of cycles and more. Different ensembles of bubbles leads to differing proposed mechanisms for tissue damage. Control of the damaged area is due to the threshold phenomena associated with the nucleation and the large focal gain in the main lobe, where the tissue disruption can be confined to fractions of the lateral beam width with little collateral damage. In addition, manipulation of the residual nuclei from a given ultrasound pulse can control cavitation events in subsequent pulses to allow greater and more uniform effects. The degree of tissue damage is equally impressive where disruption can be down to the subcellular level. At the same time, ultrasound parameters can be adjusted to selectively spare larger vessels from damage or retain the extracellular matrix. This variety of histotripsy properties opens up numerous potential medical applications, which will be discussed along with the conditions needs to achieve controlled and effective tissue disruption.

Experimental study of delivery of humidified-warm carbon dioxide during open abdominal surgery.

BackgroundThe aim of this study was to monitor the effect of humidified‐warm carbon dioxide (HWCO2) delivered into the open abdomen of mice, simulating laparotomy.MethodsMice were anaesthetized, ventilated and subjected to an abdominal incision followed by wound retraction. In the experimental group, a diffuser device was used to deliver HWCO2; the control group was exposed to passive air flow. In each group of mice, surgical damage was produced on one side of the peritoneal wall. Vital signs and core temperature were monitored throughout the 1‐h procedure. The peritoneum was closed and mice were allowed to recover for 24 h or 10 days. Tumour cells were delivered into half of the mice in each cohort. Tissue was then examined using scanning electron microscopy and immunohistochemistry.ResultsPassive air flow generated ultrastructural damage including mesothelial cell bulging/retraction and loss of microvilli, as assessed at 24 h. Evidence of surgical damage was still measurable on day 10. HWCO2 maintained normothermia, whereas open surgery alone led to hypothermia. The degree of tissue damage was significantly reduced by HWCO2 compared with that in controls. Peritoneal expression of hypoxia inducible factor 1α and vascular endothelial growth factor A was lowered by HWCO2. These effects were also evident at the surgical damage sites, where protection from tissue trauma extended to 10 days. HWCO2 did not reduce tumorigenesis in surgically damaged sites compared with passive air flow.ConclusionHWCO2 diffusion into the abdomen in the context of open surgery afforded tissue protection and accelerated tissue repair in mice, while preserving normothermia. Surgical relevanceDamage to the peritoneum always occurs during open abdominal surgery, by exposure to desiccating air and by mechanical trauma/damage owing to the surgical intervention. Previous experimental studies showed that humidified‐warm carbon dioxide (HWCO2) reduced peritoneal damage during laparoscopic insufflation. Additionally, this intervention decreased experimental peritoneal carcinomatosis compared with the use of conventional dry‐cold carbon dioxide.In the present experimental study, the simple delivery of HWCO2 into the open abdomen reduced the amount of cellular damage and inflammation, and accelerated tissue repair. Sites of surgical intervention serve as ideal locations for cancer cell adhesion and subsequent tumour formation, but this was not changed measurably by the delivery of HWCO2.

Neuroinflammation in Ischemic Pediatric Stroke

Over the last decades, the importance of inflammatory processes in pediatric stroke have become increasingly evident. Ischemia launches a cascade of events: activation and inhibition of inflammation by a large network of cytokines, adhesion and small molecules, protease, and chemokines. There are major differences in the neonatal brain compared to adult brain, but developmental trajectories of the process during childhood are not yet well known. In neonatal stroke ischemia is the leading pathophysiology, but infectious and inflammatory processes have a significant input into the course and degree of tissue damage. In childhood, beside inflammation lanced by ischemia itself, the event of ischemia might be provoked by an underlying inflammatory pathophysiology: transient focal arteriopathy, dissection, sickle cell anemia, Moyamoya and more generalized in meningitides, generalized vasculitis or genetic arteriopathies (as in ADA2). Focal inflammatory reactions tend to be located in the distal part of the carotid artery or the proximal medial arteries, but generalized processes rather tend to affect the small arteries.

Posterolateral vs Direct Anterior Approach in Total Hip Arthroplasty (POLADA Trial): A Randomized Controlled Trial to Assess Differences in Serum Markers

BackgroundThe direct anterior approach (DAA) for total hip arthroplasty has claimed to be a true tissue-sparing minimally invasive approach that has less tissue damage and a faster recovery when compared to the posterolateral approach (PLA). The aim of this randomized controlled trial is to measure the differences in serum markers and functional outcomes between the DAA and PLA for total hip arthroplasty. MethodsForty-six patients were prospectively included and randomized for either the DAA (n = 23) or PLA (n = 23). All surgical procedures were performed by 3 well-trained orthopedic surgeons. The degree of tissue damage was assessed by measuring creatine kinase (CK) and C-reactive protein levels (CRP) preoperatively and 2 hours, 1 day, 2 weeks, and 6 weeks postoperatively. Generalized linear mixed models analyses were used to assess differences between serum markers over time; correction for possible confounding factors was performed. The Hip disability and Osteoarthritis Outcome Score and the Harris Hip Score were assessed preoperatively and 6 weeks postoperatively. ResultsThere were no differences in patient demographics. The DAA had a longer operative time (P = .001). CK and CRP levels increased postoperatively, but no significant differences between the groups were found on any of the time points. Functional outcomes were also similar in both approaches. ConclusionNo difference in tissue damage measured with serum markers CK and CRP were found between the DAA and PLA for total hip arthroplasty.

Biochemical and proteomic analyses of the physiological response induced by individual housing in gilts provide new potential stress markers.

BackgroundThe objective assessment of animal stress and welfare requires proper laboratory biomarkers. In this work, we have analyzed the changes in serum composition in gilts after switching their housing, from pen to individual stalls, which is generally accepted to cause animal discomfort.ResultsBlood and saliva samples were collected a day before and up to four days after changing the housing system. Biochemical analyses showed adaptive changes in lipid and protein metabolism after the housing switch, whereas cortisol and muscular markers showed a large variability between animals. 2D-DIGE and iTRAQ proteomic approaches revealed variations in serum protein composition after changing housing and diet of gilts. Both techniques showed alterations in two main homeostatic mechanisms: the innate immune and redox systems. The acute phase proteins haptoglobin, apolipoprotein A-I and α1-antichymotrypsin 3, and the antioxidant enzyme peroxiredoxin 2 were found differentially expressed by 2D-DIGE. Other proteins related to the innate immune system, including lactotransferrin, protegrin 3 and galectin 1 were also identified by iTRAQ, as well as oxidative stress enzymes such as peroxiredoxin 2 and glutathione peroxidase 3. Proteomics also revealed the decrease of apolipoproteins, and the presence of intracellular proteins in serum, which may indicate physical injury to tissues.ConclusionsHousing of gilts in individual stalls and diet change increase lipid and protein catabolism, oxidative stress, activate the innate immune system and cause a certain degree of tissue damage. We propose that valuable assays for stress assessment in gilts may be based on a score composed by a combination of salivary cortisol, lipid metabolites, innate immunity and oxidative stress markers and intracellular proteins.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-016-0887-1) contains supplementary material, which is available to authorized users.