Cut or burnt? – Categorizing morphological characteristics of heat-induced fractures and sharp force trauma

Distinguishing trauma from heat-induced fractures is a challenge faced by forensic anthropologists and pathologists during medicolegal investigations in which fire has been used by the perpetrators to destroy evidence. This paper aims to validate the provided identification features to distinguish between fire induced alterations and sharp force trauma.A total of 80 cremated adult individuals were used in this paper: 3 recently deceased embalmed cadavers from Cementerio Sur de Madrid for the sharp force trauma experiment in which 55 pre-burning injuries were inflicted using a machete and a serrated knife in different anatomical regions. And 77 cremated individuals from the Forensic Anthropology and Odontology Laboratory osteological collection. Five cremated long bones from this collection were selected, and 10 cuts were manually inflicted using a serrated knife to analyse post-burning trauma. Heat-induced changes and trauma morphologic characteristics were thus documented and analysed. The examination and documentation of morphological traits enabled the production of a heat-induced changes visual guide and a flow-chart. Two intraclass correlation tests were performed to validate the capacity of the observer to distinguish between fire related alterations and toolmarks.The results obtained in the statistical analysis indicate that, even if the toolmarks are visible and recognizable upon macroscopic observation by the observers, some features, such as the step and the transverse fractures can be mistaken with inflicted trauma. The use of the proposed features coupled with careful anthropological examination is recommended and has been found functional for participants with no prior knowledge in the analysis of cremated remains.     

Thermoregulatory responses to ice slurry ingestion during low and moderate intensity exercises with restrictive heat loss

ObjectivesWe investigated the thermoregulatory responses to ice slurry ingestion during low- and moderate-intensity exercises with restrictive heat loss.DesignRandomised, counterbalanced, cross-over design.MethodsFollowing a familiarisation trial, ten physically active males exercised on a motorised treadmill at low-intensity (L; 40% VO_2max) or moderate-intensity (M; 70% VO_2max) for 75-min, in four randomised, counterbalanced trials. Throughout the exercise bout, participants donned a raincoat to restrict heat loss. Participants ingested 2 g kg^?1 body mass of ambient water (L + AMB and M + AMB trials) or ice slurry (L + ICE and M + ICE trials) at 15-min intervals during exercise in environmental conditions of T_db, 25.1 ± 0.6 °C and RH, 63 ± 5%. Heart rate (HR), gastrointestinal temperature (T_gi), mean weighted skin temperature (T_sk), estimated sweat loss, ratings of perceived exertion (RPE) and thermal sensation (RTS) were recorded.ResultsCompared to L + AMB, participants completed L + ICE trials with lower ΔT_gi (0.8 ± 0.3°C vs 0.6 ± 0.2 °C; p = 0.03), mean RPE (10 ± 1 vs 9 ± 1; p = 0.03) and estimated sweat loss (0.91 ± 0.2 L vs 0.78 ± 0.27 L; p = 0.04). Contrastingly, T_gi (p = 0.22), T_sk (p = 0.37), HR (p = 0.31), RPE (p = 0.38) and sweat loss (p = 0.17) were similar between M + AMB and M + ICE trials. RTS was similar during both low-intensity (4.9 ± 0.5 vs 4.7 ± 0.3; p = 0.10) and moderate-intensity exercise (5.3 ± 0.47 vs 5.0 ± 0.4; p = 0.09).ConclusionsPer-cooling using ice slurry ingestion marginally reduced thermal strain during low-intensity but not during moderate-intensity exercise. Ice slurry may be an effective and practical heat mitigation strategy during low-intensity exercise such as in occupational and military settings, but a greater volume should be considered to ensure its efficacy.     

Chaperone therapy for molecular pathology in lysosomal diseases

In lysosomal diseases, enzyme deficiency is caused by misfolding of mutant enzyme protein with abnormal steric structure that is expressed by gene mutation. Chaperone therapy is a new molecular therapeutic approach primarily for lysosomal diseases. The misfolded mutant enzyme is digested rapidly or aggregated to induce endoplasmic reticulum stress. As a result, the catalytic activity is lost. The following sequence of events results in chaperone therapy to achieve correction of molecular pathology. An orally administered low molecular competitive inhibitor (chaperone) is absorbed into the bloodstream and reaches the target cells and tissues. The mutant enzyme is stabilized by the chaperone and subjected to normal enzyme protein folding (proteostasis). The first chaperone drug was developed for Fabry disease and is currently available in medical practice. At present three types of chaperones are available: competitive chaperone with enzyme inhibitory bioactivity (exogenous), non-competitive (or allosteric) chaperone without inhibitory bioactivity (exogenous), and molecular chaperone (heat shock protein; endogenous). The third endogenous chaperone would be directed to overexpression or activated by an exogenous low-molecular inducer. This new molecular therapeutic approach, utilizing the three types of chaperone, is expected to apply to a variety of diseases, genetic or non-genetic, and neurological or non-neurological, in addition to lysosomal diseases.     

Heat shock protein is a key therapeutic target for nerve repair in autoimmune peripheral neuropathy and severe peripheral nerve injury

Guillain-Barré syndrome (GBS) is an autoimmune peripheral neuropathy and a common cause of neuromuscular paralysis. Preceding infection induces the production of anti-ganglioside (GD) antibodies attacking its own peripheral nerves. In severe proximal peripheral nerve injuries that require long-distance axon regeneration, motor functional recovery is virtually nonexistent. Damaged axons fail to regrow and reinnervate target muscles. In mice, regenerating axons must reach the target muscle within 35 days (critical period) to reform functional neuromuscular junctions and regain motor function. Successful functional recovery depends on the rate of axon regeneration and debris removal (Wallerian degeneration) after nerve injury. The innate-immune response of the peripheral nervous system to nerve injury such as timing and magnitude of cytokine production is crucial for Wallerian degeneration. In the current study, forced expression of human heat shock protein (hHsp) 27 completely reversed anti-GD-induced inhibitory effects on nerve repair assessed by animal behavioral assays, electrophysiology and histology studies, and the beneficial effect was validated in a second mouse line of hHsp27. The protective effect of hHsp27 on prolonged muscle denervation was examined by performing repeated sciatic nerve crushes to delay regenerating axons from reaching distal muscle from 37 days up to 55 days. Strikingly, hHsp27 was able to extend the critical period of motor functional recovery for up to 55 days and preserve the integrity of axons and mitochondria in distal nerves. Cytokine array analysis demonstrated that a number of key cytokines which are heavily involved in the early phase of innate-immune response of Wallerian degeneration, were found to be upregulated in the sciatic nerve lysates of hHsp27 Tg mice at 1 day postinjury. However, persistent hyperinflammatory mediator changes were found after chronic denervation in sciatic nerves of littermate mice, but remained unchanged in hHsp27 Tg mice. Taken together, the current study provides insight into the development of therapeutic strategies to enhance muscle receptiveness (reinnervation) by accelerating axon regeneration and Wallerian degeneration.     

Hyperreactivity of Neutrophils and Abnormal T Cell Homeostasis: a New Insight for Pathogenesis of Behçet's Disease

Neutrophil hyperfunction of Behçet's disease is in part regulated by genetical factors, especially related to HLA-B51 genes and by immunological abnormalities. Regarding the latter points, Behçet's disease worsens with abnormal regulation by γδ T cells and αβ T cells. Indeed, our own studies and those of other laboratories suggest that human heat shock protein may be one of the triggering factors for activation of both the γδ T cells and αβ T cells. These activated T cells may produce proinflammatory and/or inflammatory cytokines, and lead to tissue injury possibly via delayed-type hypersensitivity reaction, macrophage activation, and activation and/or recruitment of neutrophils. Here we discuss the crosstalk between the immune system and neutrophils in this disease.     

Extended glaze firings for porcelain-veneered zirconia: Effects on the mechanical and optical behavior

ObjectiveThis study evaluated the effect of dwell time (conventional or extended) and cooling protocol (fast or slow) of self-glaze firings on the mechanical (flexural strength and crack propagation) and optical (color and translucency) properties of a porcelain-veneered zirconia system.MethodsBilayer disc-shaped samples were prepared (Vita VM9 + In-Ceram YZ) and divided according to the final thermal treatment: glaze firing followed by slow cooling (furnace opening at 200 °C) (G-S) or fast cooling (furnace opening at 600 °C) (G-F, manufacturer-recommended protocol), extended glaze firing (15 min of dwell time) followed by slow cooling (EG-S) or fast cooling (EG-F), or no thermal treatment (CTRL). Porcelain roughness (Ra and Rz) was measured before and after glaze firings. Color (ΔE₀₀) and translucency (TP₀₀) alteration were also evaluated. Flexural strength was measured with the piston-on-three-ball test and crack propagation analysis was performed after Vickers indentations. Complementary analyzes of crystalline phase and scanning electron microscopy were carried out.ResultsSignificant effect of dwell time was observed, with extended glaze leading to higher flexural strength and shorter crack lengths. Cracks of EG groups were observed to end in clusters of crystals. Color and translucency changed below perceptibility thresholds. All treatments led to a smoother surface and EG groups reached the lowest Rz values. An extra SiO₂ peak was revealed in control and EG groups. No effect of cooling protocol was found.SignificanceExtended glaze firing was able to improve the resistance to crack initiation and propagation of porcelain-veneered zirconia without clinically perceptible changes in optical properties.     

Expression of heat shock proteins 70 and 47 in tissues following short-pulse laser irradiation: Assessment of thermal damage and healing

In order to develop effective laser-based therapeutics, the extent of laser-induced damage must be quantified for given laser parameters. Therefore, we want to determine the spatiotemporal expression patterns of heat shock proteins, both to understand the roles of heat shock proteins in laser-induced tissue damage and repair and to develop heat shock proteins as tools to illustrate the extent of laser-induced damage and wound healing following irradiation. We exposed anesthetized mice to the focused beam of a short-pulse Nd:YAG laser (1064 nm; 200 ns pulsewidth) for 15 s, while measuring temperature distribution in the skin using an infrared thermal camera. Following irradiation, we examined expression of HSP47 and HSP70 over time (0–24 h) as indicators of the heat shock response and recovery from damage in the laser-irradiated region. Expression patterns of HSP70 and HSP47 as detected by immunohistochemistry and confocal microscopy delineate the extent of damage and the process of healing in tissue. Both HSP70 and HSP47 were expressed in dermis and epidermis following laser irradiation, and the spatial and temporal changes in HSP expression patterns define the laser-induced thermal damage zone and the process of healing in tissues. HSP70 may define biochemically the thermal damage zone in which cells are targeted for destruction, and HSP47 may illustrate the process of recovery from thermally induced damage. Studying the effects of different laser parameters on the expression of HSPs will allow development of effective laser therapies that provide accurate and precise tissue ablation and may promote rapid wound healing following laser-based surgery.     

Design and encapsulation of anticancer dual HSP27 and HER2 inhibitor into low density lipoprotein to target ovarian cancer cells

Tumor cells overexpress low-density lipoprotein (LDL) receptors (LDL-r). Hence, LDL is proposed as a targeting shuttle of anticancer drugs. Therefore, the objective of this study was to synthesize a dual inhibitor of heat shock protein 27 (HSP27) and human epidermal growth factor receptor 2 (HER2) conjugated with cholesterol and encapsulated into LDL for selective targeting of ovarian cancer cells. In the present study, the anticancer agent and its cholesterol conjugate were successfully prepared and characterized physically for color, shape, and melting point. Moreover, the compounds were chemically characterized for ¹H NMR and ¹³C NMR spectra using FTIR and LCMS/MS. Our results revealed that the prepared anticancer agent and its cholesterol conjugate elicited dual HSP27 and HER2 inhibition, as confirmed using western blotting. The anticancer agent (compound D) entered cells and targeted the HSP27 function, thereby reducing HER2 expression. However, a cholesterol-conjugated anticancer agent (compound F) had high cellular uptake and inhibited the growth of SKOV3 cells after encapsulation into LDL. The obtained results concluded that the design of an LDL-encapsulated cholesterol-conjugated HSP27-HER2 dual inhibitor may be a promising approach to realize specific targeted achieve killing of ovarian cancer.     

艾灸足三里和梁门穴诱导热休克蛋白70抗大鼠胃黏膜氧化损伤作用

目的:观察艾灸足三里和梁门穴对应激性溃疡大鼠胃黏膜热休克蛋白70(HSP70)表达的影响,探讨艾灸足阳明经穴抗胃黏膜氧化损伤的作用机制.方法:将SD大鼠60只完全随机平均分为空白组、模型组、艾灸足三里等穴组和艾灸非穴对照点组,采用水浸-束缚应激法制备应激性溃疡模型.按Guth法计算胃黏膜损伤指数(UI),用激光多普勒血流仪测定胃黏膜血流量(GMBF),用免疫组织化学法和硫代巴比妥酸染色法对处理后大鼠检测其胃黏膜HSP70的表达和丙二醛(MDA)的含量.结果:与模型组和艾灸非穴组比较,艾灸足三里等穴可使应激性溃疡大鼠胃黏膜损伤指数明显下降(14.100±5.425vs26.800±9.807,26.200±7.729,P<0.01),HSP70表达上调(0.133±0.035vs0.077±0.057,0.059±0.038,P<0.01)、血流量增高(279.827±172.862mL/minvs139.489±33.133,141.512±58.450mL/min,P<0.05)、MDA含量减少(2.586±0.252μmol/Lvs3.906±0.768,3.464±1.502μmol/L,P<0.05).结论:艾灸足三里和梁门穴能诱导胃黏膜HSP70高表达并降低MDA含量,以达到其抗氧化损伤作用,并有相对的穴位特异性.