Artificial intelligence generated clinical score sheets: looking at the two faces of Janus.

In vivo experiments are increasingly using clinical score sheets to ensure minimal distress to the animals. A score sheet is a document that includes a list of specific symptoms, behaviours and intervention guidelines, all balanced to for an objective clinical assessment of experimental animals. Artificial Intelligence (AI) technologies are increasingly being applied in the field of preclinical research, not only in analysis but also in documentation processes, reflecting a significant shift towards more technologically advanced research methodologies. The present study explores the application of Large Language Models (LLM) in generating score sheets for an animal welfare assessment in a preclinical research setting. Focusing on a mouse model of inflammatory bowel disease, the study evaluates the performance of three LLM - ChatGPT-4, ChatGPT-3.5, and Google Bard - in creating clinical score sheets based on specified criteria such as weight loss, stool consistency, and visible fecal blood. Key parameters evaluated include the consistency of structure, accuracy in representing severity levels, and appropriateness of intervention thresholds. The findings reveal a duality in LLM-generated score sheets: while some LLM consistently structure their outputs effectively, all models exhibit notable variations in assigning numerical values to symptoms and defining intervention thresholds accurately. This emphasizes the dual nature of AI performance in this field-its potential to create useful foundational drafts and the critical need for professional review to ensure precision and reliability. The results highlight the significance of balancing AI-generated tools with expert oversight in preclinical research.

The Role of Mesenchymal Stem Cells in the Treatment of a Chronic Rhinosinusitis-An In Vivo Mouse Model.

Objectives/Hypothesis: It is acknowledged that the treatment of chronic rhinosinusitis (CRS) represents an important challenge for rhinology and for social and economic life. At present, one of the most common treatments for CRS is represented by local corticosteroids followed by endoscopic sinus surgery (ESS). Starting from the example of the mesenchymal stem cell's (MSC) capacity to migrate and to modulate a real response in the nasal mucosa of an allergic rhinitis mouse model, we try to obtain a response in a CRS mouse model, using MSC derived by adipose tissue. The aim of this study is to demonstrate that the MSC can be used in CRS treatment and could change its priorities. Methods: Seventy female mice (6 MSC donor mice) were randomized in two stages of study, 32 Aspergillus fumigatus (Af) exposure mice (20 for histological comparison to 1st control mice and 12 for MSC administration, to CRS/MCS model) and 32 control mice (20 for histological comparison to CRS model and 12 for MSC administration and histological control to MSC model); in the first stage, the Aspergillus fumigatus (Af) CRS mouse model was targeted, in this section were included 64 (n = 32) mice (treated and control group). In order to assess the inflammation level (histological analysis), the animals were euthanized; in the second stage MSCs (1 × 106/animal) were administered intravenously to a total of 24 (n = 24) mice (12 mice from the exposed group and 12 mice from the second control group). Results: After 12 weeks of Af intranasal instillation, the inflammation parameters evaluated indicated a severe diffuse chronic inflammation, associated with diffuse severe hyperplasia and mature diffuse squamous metaplasia. The MSCs' injection via the ophthalmic vein induced important histopathological changes in the CRS experimental group, starting with the presence of MSCs in all samples and continuing with the important degenerative character of inflammation. Conclusions: MSC administration demonstrated a real improvement of CRS evolution on the CRS mouse model.

Effect of Lactobacillus plantarum ACTT 8014 on 5-fluorouracil induced intestinal mucositis in Wistar rats.

Some previous studies reported that probiotics might decrease the severity of chemotherapy-induced mucositis. This study assessed the potential protective effect of Lactobacillus plantarum ATCC 8014 on 5-fluorouracil (5-FU) induced intestinal mucositis in the Wistar rats. The Crl:WI rats were divided into two groups of six animals (F, L) and one group of 5 animals (M). Group L received for 9 days 3.32x109 CFU/ml of Lactobacillus plantarum orally. In the 7th day of the experiment 400 mg of 5-FU was administered intraperitoneally in groups L and F. Group M received only the vehicles. All animals were sacrificed in the 9th day. Eleven histological characteristics of mucositis were quantified from 0 (normal) to 3 (severe) for duodenum, jejunum and colon. Semiquantitative grades measured Toll-like receptor 4 (TLR4) immunopositive cells. The independent groups were analyzed using the Kruskal-Wallis test, Mann-Whitney U test, with a Bonferroni correction for alpha (P≤0.016). In the group F, treated with 5-FU, the most affected areas were the jejunum and the duodenum. The medium score of histological lesions was 27 for jejunum (minimum 25, maximum 32) and 21 for duodenum (minimum 18, maximum 29). Graded microscopic mucosal changes of the jejunum were significantly lower in group L compared with group F (U=0, P=0.009, Mann-Whitney test). The histological changes depicted on the duodenal and colonic mucosa were less severe in group L than in group F, but without reaching the statistical significance (duodenum: U=6, P=0.172, Mann-Whitney test; colon: U=12, P=0.916, Mann-Whitney test). Although the TLR4 immunoexpression was more intense in group L, no significant statistical difference was revealed at duodenum, jejunum or colonic mucosa. Significantly fewer microscopic changes were depicted in L group on the jejunum, suggesting a potential beneficial effect of Lactobacillus plantarum at this level in 5-FU induced mucositis.

MicroRNA-155-5p Plays a Critical Role in Transient Leukemia of Down Syndrome by Targeting Tumor Necrosis Factor Receptor Superfamily Members.

BACKGROUND/AIMS: Down syndrome associated disorders are caused by a complex genetic context where trisomy 21 is a central component in relation to other changes involving epigenetic regulators and signaling molecules. This unique genetic context is responsible for the predisposition of people with Down syndrome to acute leukemia. Although, the research in this field has discovered some important pathogenic keys, the exact mechanism of this predisposition is not known. METHODS: In this study we applied functional enrichment analysis to evaluate the interactions between genes localized on chromosome 21, genes already identify as having a key role in acute leukemia of Down syndrome, miRNAs and signaling pathways implicated in cancer and cell development and found that miR-155 has a high impact in genes present on chromosome 21. Forward, we performed next generation sequencing on DNA samples from a cohort of patients diagnosed with acute leukemia of Down syndrome and in vitro functional assay using a CMK-86 cell line, transfected with either mimic or inhibitor of the microRNA-155-5p. RESULTS: Our results show that the epigenetic alteration of the TNF superfamily receptors in Down syndrome, which can be correlated to microRNA-155-5p aberrant activity, may play an important role in cell signaling and thus be linked to acute myeloid leukemia. CONCLUSION: Some genes, already shown to be mutated in AML-DS, are potential targets for miR-155. Our results show that the epigenetic alteration of the TNF superfamily receptors in Down syndrome may play an important role in cell signaling and thus be linked to acute myeloid leukemia.

B Cells versus T Cells in the Tumor Microenvironment of Malignant Lymphomas. Are the Lymphocytes Playing the Roles of Muhammad Ali versus George Foreman in Zaire 1974?

Malignant lymphomas are a heterogeneous group of malignancies that develop both in nodal and extranodal sites. The different tissues involved and the highly variable clinicopathological characteristics are linked to the association between the lymphoid neoplastic cells and the tissues they infiltrate. The immune system has developed mechanisms to protect the normal tissue from malignant growth. In this review, we aim to explain how T lymphocyte-driven control is linked to tumor development and describe the tumor-suppressive components of the resistant framework. This manuscript brings forward a new insight with regard to intercellular and intracellular signaling, the immune microenvironment, the impact of therapy, and its predictive implications. A better understanding of the key components of the lymphoma environment is important to properly assess the role of both B and T lymphocytes, as well as their interplay, just as two legendary boxers face each other in a heavyweight title final, as was the case of Ali versus Foreman.

Transforming growth factor ß-mediated micromechanics modulates disease progression in primary myelofibrosis.

Primary myelofibrosis (PMF) is a Ph-negative myeloproliferative neoplasm (MPN), characterized by advanced bone marrow fibrosis and extramedullary haematopoiesis. The bone marrow fibrosis results from excessive proliferation of fibroblasts that are influenced by several cytokines in the microenvironment, of which transforming growth factor-ß (TGF-ß) is the most important. Micromechanics related to the niche has not yet been elucidated. In this study, we hypothesized that mechanical stress modulates TGF-ß signalling leading to further activation and subsequent proliferation and invasion of bone marrow fibroblasts, thus showing the important role of micromechanics in the development and progression of PMF, both in the bone marrow and in extramedullary sites. Using three PMF-derived fibroblast cell lines and transforming growth factor-ß receptor (TGFBR) 1 and 2 knock-down PMF-derived fibroblasts, we showed that mechanical stress does stimulate the collagen synthesis by the fibroblasts in patients with myelofibrosis, through the TGFBR1, which however seems to be activated through alternative pathways, other than TGFBR2.

Effects of Lycium barbarum L. Polysaccharides on Inflammation and Oxidative Stress Markers in a Pressure Overload-Induced Heart Failure Rat Model.

Despite recent advances in disease management and prevention, heart failure (HF) prevalence is still high. Hypertension, inflammation and oxidative stress are being investigated as important causative processes in HF. L. barbarum L. polysaccharides (LBPs) are widely used for their anti-inflammatory and antioxidant properties. Thus, the aim of the present study was to evaluate the effects of LBPs on inflammation and oxidative stress markers in a pressure overload-induced HF rat model, surgically induced by abdominal aorta banding in Wistar rats (AAB) (n = 28). Also, control rats (n = 10) were subjected to a sham operation. After echocardiographic confirmation of HF (week 24), AAB rats were divided into three groups: rats treated with LBPs for 12 weeks: 100 mg/kg body weight /day (AAB_100, n = 9), 200 mg/kg body weight /day (AAB_200, n = 7) and no-treatment group (control AAB, n = 12). After 12 weeks of treatment with LBPs, the decline of cardiac function was prevented compared to the control AAB rats. Treatment with 200 mg/kg body weight /day LBPs significantly reduced the inflammation as seen by cytokine levels (IL-6 and TNF-α) and the plasma lipid peroxidation, as seen by malondialdehyde levels. These results suggest that LBPs present anti-inflammatory and antioxidant effects with utility in a HF animal model and encourage further investigation of the cardioprotective effects of these polysaccharides.

KRAS/NRAS/BRAF Mutations as Potential Targets in Multiple Myeloma.

In multiple myeloma the mutational profile is mainly represented by translocations involving chromosome 14 and by single nucleotide mutations, frequently involving genes implicated in the mitogen activated protein kinase (MAPK) pathway, as KRAS, NRAS, and, less frequently, BRAF. Because KRAS/NRAS/BRAF mutations are associated with a higher number of mutations per patient, we hypothesize that this group of patients could benefit from therapy with checkpoint inhibitors because of the higher frequency of neo-antigens that this group would present. This might also true for IMiD therapy, because of their activatory effect on T cells. Because, KRAS/NRAS/BRAF are members of the MAPK pathway, this subgroup of patients would also benefit from inhibitors of MAPK, either directly on the specific mutation or through downstream targeting of MEK1/2 or ERK1/2 to account for a possible compensatory collateral signaling that might activate as response to upstream inhibition.

The Effects of Postoperative Astaxanthin Administration on Nasal Mucosa Wound Healing.

. BACKGROUND: Wound healing of the nasal mucosa after endoscopic sinus surgery (ESS) is frequently complicated by scaring and consequently recurrences are encountered. Methods of optimizing results have been sought. In the present study we evaluated the effects of a powerful antioxidant, astaxanthin, on nasal mucosa healing after surgery, comparing it to the extensively studied properties of dexamethasone. MATERIALS AND METHODS: 63 Wistar rats were used. The nasal mucosa from one side was damaged employing the brushing method. They were randomly divided into three experimental groups, one treated with astaxanthin, the second treated with dexamethasone and the third one acted as the control and was given normal saline. The rats were killed on days 5, 14 and 28 following injury. We observed the temporal evolution of the wound healing process and quantified the results by assessing four parameters: the epithelial thickness index (ETI), the subepithelial thickness index (STI), the goblet cell count and the subepithelial fibrosis index (SFI). RESULTS: At 28 days, the ETI was significantly lower in the astaxanthin group (p < 0.05) compared to the other two groups. The STI was also lower in the astaxanthin group (p < 0.05), but comparable to the dexamethasone group at 28 days. The goblet cell count was higher in the astaxanthin group. The SFI had similar results in both dexamethasone and astaxanthin groups, with lower values compared to the control group. In the astaxanthin group there was no synechia formation. CONCLUSION: Astaxanthin given in the post injury period significantly decreases fibrosis, inhibits synechia development and significantly decreases subepithelial fibrosis. Moreover, it has no general or local toxic effects.

Enhancement of bone consolidation using high-frequency pulsed electromagnetic short-waves and titanium implants coated with biomimetic composite embedded into PLA matrix: in vivo evaluation.

PURPOSE: Bone consolidation after severe trauma is the most challenging task in orthopedic surgery. This study aimed to develop biomimetic composite for coating Ti implants. Afterwards, these implants were tested in vivo to assess bone consolidation in the absence or the presence of high-frequency pulsed electromagnetic short-waves (HF-PESW). MATERIALS: Biomimetic coating was successfully developed using multi-substituted hydroxyapatite (ms-HAP) functionalized with collagen (ms-HAP/COL), embedded into poly-lactic acid (PLA) matrix (ms-HAP/COL@PLA), and subsequently covered with self-assembled COL layer (ms-HAP/COL@PLA/COL, named HAPc). METHODS: For in vivo evaluation, 32 Wistar albino rats were used in four groups: control group (CG) with Ti implant; PESW group with Ti implant+HF-PESW; HAPc group with Ti implant coated with HAPc; HAPc+PESW group with Ti implant coated with HAPc+HF-PESW. Left femoral diaphysis was fractured and fixed intramedullary. From the first post-operative day, PESW and HAPc+PESW groups underwent HF-PESW stimulation for 14 consecutive days. Biomimetic coating was characterized by XRD, HR-TEM, SEM, EDX and AFM. RESULTS: Osteogenic markers (ALP and osteocalcin) and micro-computed tomography (CT) analysis (especially bone volume/tissue volume ratio results) indicated at 2 weeks the following group order: HAPc+PESW>HAPc≈PESW (P>0.05) and HAPc+PESW>control (P<0.05), indicating the higher values in HAPc+PESW group compared to CG. The fracture-site bone strength showed, at 2 weeks, the highest average value in HAPc+PESW group. Moreover, histological analysis revealed the most abundant COL fibers assembled in dense bundles in HAPc-PESW group. At 8 weeks, micro-CT indicated higher values only in HAPc+PESW group vs CG (P<0.05), and histological results showed a complete-healed fracture in groups: HAPc+PESW, HAPc and PESW, but with more advanced bone remodeling in HAPc+PESW group. CONCLUSION: Using Ti implants coated by HAPc jointly with HF-PESW stimulation positively influenced the bone consolidation process, especially in its early phase, thus potentially providing a superior strategy for clinical applications.

Enhancement of bone consolidation using high-frequency pulsed electromagnetic fields (HF-PEMFs): An experimental study on rats.

In vitro studies showed that high-frequency pulsed electromagnetic fields (HF-PEMFs) increase the activity/expression of early and late osteogenic markers and enhance bone mineralization. The main aim of this study was to investigate the in vivo effects of HF-PEMFs on fracture healing using a rat model. A femur fracture was established by surgery in 20 male Wistar rats. Titanium nails were implanted to reduce and stabilize the fracture. After surgery, 20 rats were equally divided into untreated control and treated group (from the first postoperative day HF-PEMFs at 400 pulses/sec [pps] were applied for 10 minutes/day, for two weeks). Quantitative and qualitative assessment of bone formation was made at two and eight weeks following surgery and included morphological and histological analysis, serological analysis by ELISA, micro-computed tomography (micro-CT), and three-point bending test. At two weeks in HF-PEMF group, soft callus was at a more advanced fibrocartilaginous stage and the bone volume/total tissue volume (BV/TV) ratio in the callus area was significantly higher compared to control group (p = 0.047). Serum concentration of alkaline phosphatase (ALP) and osteocalcin (OC) was significantly higher in HF-PEMF group (ALP p = 0.026, OC p = 0.006) as well as the mechanical strength of femurs (p = 0.03). At eight weeks, femurs from HF-PEMF group had a completely formed woven bone with dense trabeculae, active bone marrow, and had a significantly higher BV/TV ratio compared to control (p = 0.01). HF-PEMFs applied from the first postoperative day, 10 minutes/day for two weeks, enhance bone consolidation in rats, especially in the early phase of fracture healing.

Osseointegration of titanium scaffolds manufactured by selective laser melting in rabbit femur defect model.

The aim of this study was to assess the osseointegration of two series of titanium (Ti) scaffolds with 0.8 and 1 mm cell size obtained by Selective Laser Melting (SLM) technique. One of the series had the Ti surface unmodified, while the other had the Ti surface coated with silicon-substituted nano-hydroxyapatite (nano-HapSi). The scaffolds were implanted in the femur bone defects of 6 White Californian male rabbits: three animals were implanted with 0.8 mm cell size scaffolds and three animals with 1 mm cell size scaffolds, respectively. The bone fragments and scaffolds harvested at 2, 4 and 6 months were histologically analyzed using conventional light microscopy (LM) and scanning electron microscopy (SEM) for the qualitative evaluation of the bone tissue formed in contact with the scaffold. Both LM and SEM images indicated a better osseointegration for nano-HapSi coated Ti scaffolds. LM revealed that the compact bone formed in the proximity of nano-HapSi-coated scaffolds was better organized than spongy bone associated with unmodified scaffolds. Moreover, Ti scaffolds with meshes of 0.8 mm showed higher osseointegration compared with 1 mm. SEM images at 6 months revealed that the bone developed not only in contact with the scaffolds, but also proliferated inside the meshes. Nano-HapSi-coated Ti implants with 0.8 mm meshes were completely covered and filled with new bone. Ti scaffolds osseointegration depended on the mesh size and the surface properties. Due to the biocompatibility and favorable osseointegration in bone defects, nano-HapSi-coated Ti scaffolds could be useful for anatomical reconstructions.

Periodontal disease may induce liver fibrosis in an experimental study on Wistar rats.

BACKGROUND: The aim was to assess the effects of periodontal disease in promoting liver fibrosis in a rat model of ligature-induced periodontitis. METHODS: Twenty-four Wistar rats were divided into four groups: control (CTRL), experimental periodontitis group at day 7 (PER7), at day 14 (PER14), at day 21 (PER21). Experimental periodontitis was induced by the placement of a silk ligature around mandibular incisors. The following parameters were assessed: gingival index, tooth mobility; liver status, and portal vein caliber by ultrasound examination; bone retraction, bone mineral density (BMD), bone volume/tissue volume (BV/TV) by micro-CT analysis; aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT); oxidative stress (malondialdehyde [MDA], reduced glutathione/oxidative glutathione ratio [GSH/GSSG]), and matrix metalloproteinase-8 (MMP-8) levels; and histopathological evaluation of periodontal and liver tissues. RESULTS: Periodontal parameters showed the development of periodontitis in experimental groups. Micro-CT results indicates an increase of bone retraction and BMD values and a decrease of BV/TV value in PER groups. Liver fibrosis could not be diagnosed with ultrasound examination in any of the groups. Elevated levels of ASAT and ALAT in PER groups compared with CTRL group were found. MDA have indicated elevated levels and a decrease of GSH/GSSG ratio in PER group compared with the CTRL group. Levels of MMP-8 have indicated high values in PER21 compared with the other groups. Histological analysis of the periodontal and liver tissues sustains the link between periodontal and hepatic injury. CONCLUSION: This study demonstrates a positive correlation between periodontal lesions and liver disease. Periodontitis may be an independent risk factor for liver fibrosis.

Correction: Genetically enhanced T lymphocytes and the intensive care unit.

[This corrects the article DOI: 10.18632/oncotarget.24637.].

Exosome-carried microRNA-based signature as a cellular trigger for the evolution of chronic lymphocytic leukemia into Richter syndrome.

Even if considered a cumulative and not a proliferative CD5+ B-cell neoplasm, chronic lymphocytic leukemia (CLL) has a proliferation rate higher than that recognized earlier, especially in the lymphoid tissues. Some patients with CLL develop a clinical syndrome entitled Richter syndrome (RS). Understanding CLL genetics and epigenetics may help to elucidate the molecular basics of the clinical heterogeneity of this type of malignancy. In the present project we aimed to identify a microRNA species that can predict the evolution of therapy-resistant CLL towards RS. In the first phase of our study, microRNA-19b was identified as a possible target, and in the second phase, we transfected three different CLL cell lines with microRNA-19b mimic and inhibitor and assessed the potential role on leukemia cells in vitro. The mechanism by which miR-19b acts were identified as the upregulation of Ki67 and downregulation of p53. This was further supported through RT-PCR and western blotting on CLL cell lines, as well as by next generation sequencing on two patients diagnosed with CLL that evolved into RS.

A micro-computed tomography study of morphological aspect of root canal instrumentation with ProTaper Next and One Shape New Generation in mandibular molars.

ProTaper Next (Dentsply Maillefer, Ballaigues, Switzerland) (PTN) and One Shape New Generation (MicroMéga, Besançon, France) (OSNG) belong to a relatively new generation of rotary nickel-titanium (NiTi) files. Scientists keep improving features of endodontic files in order to obtain anatomically shaped and cleaned root canals and avoid canal transportation, for a better outcome of the endodontic treatment. For the current study, the aim was to evaluate and assess the changes in root canal morphology after instrumentation with PTN and OSNG by using micro-computed tomography (CT). This high-tech resolution tomography allows a much more detailed analysis of the root canal anatomy and its transformation after rotary instrumentation. We have selected 10 mandibular molars; before and after canal preparation, the samples were distributed in two homogeneous groups (PTN and OSNG groups) and submitted to standardized radiographs and micro-CT (SkyScan1172, Kontich, Belgium). From the three-dimensional (3D) images obtained from the scanning, we were able to perform a two-dimensional (2D) (perimeter, area and roundness), respectively a 3D (volume, surface area, structure model index) analysis, before and after root canal instrumentation. Results did not revealed important statistical differences among the two groups in relation to the curvature and volume of the root canals before instrumentation; after rotary instrumentation, there was a substantially increase of volume and surface area for all the samples (p<0.05). The two types of instruments preserved the original canal path, maintaining a continuous, safe and adequate shape and taper of the root canals.

New alginate-pullulan-bioactive glass composites with copper oxide for bone tissue regeneration trials.

Composites based on sodium alginate, pullulan, and bioactive SiO2 -CaO-P2 O5 glass-ceramics with copper oxide were prepared as capsules. The obtained samples were structurally characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM), and their bioactivity and biocompatibility properties were also tested both in vitro and in vivo by XRD, FT-IR, SEM, and high-resolution transmission electron microscopy. The fibroblast and osteoblast cell viability assays have shown good proliferation rates for all investigated samples, whereas all composites exhibited a good in vivo tolerance. The recovered composites after 5 weeks' in vivo and in vitro trials evidenced clear macroscopic alterations; particularly, after soaking in simulated body fluid, they have a corn flake aspect, and after their in vivo inoculation, a globular shape is retained. Different crystalline shapes of hydroxyapatite were formed after in vitro and in vivo trials for the glass-ceramic-polymer composites, the in vitro precipitated apatite was found to be nodular, and the in vivo experiment led to needlelike crystallites formation. Histopathological results showed a good biocompatibility with no significant signs of rejection by the host tissue. These assessments performed on the composites indicate that the studied materials can be considered without any doubt suitable candidates for future bone regeneration applications.

Influence of Gender on Health-Related Quality of Life and Disability at 1 Year After Surgery for Thoracolumbar Burst Fractures.

STUDY DESIGN: Case series. OBJECTIVE: Thoracolumbar burst fractures (TLBF) are the most frequent type of spinal fractures. Approximately half of the patients are neurologically intact and their treatment is still debatable. Gender could influence outcome after surgical procedures, but this is still unclear in patients sustaining a spinal fracture. The aim of this study was to investigate how gender influences health-related quality of life (HRQOL) and disability in patients operated on for TLBF. METHODS: We identified 44 neurologically intact patients from a consecutive series of patients treated surgically for a single-level traumatic burst fracture (AOSpine Subaxial Classification System A3) in the thoracolumbar transition area (Th12-L2). At 1 year after surgery, they were evaluated using the SF-36v2 questionnaire to assess HRQOL and Oswestry Disability Index (ODI) questionnaire to evaluate disability. RESULTS: Male patients scored higher in each item of the SF-36v2, with significant differences (P < .05) for Physical Function (PF), Bodily Pain (BP), and Social Function (SF). Male patients also had lower disability scores. Overall ODI score had a strong correlation with Physical Function, Role-Physical, Bodily Pain, Vitality, Mental Health, and overall Physical Component Summary (PCS) of the SF-36 in women, but only with Physical Function, Role-Physical, Role-Emotional, and PCS in men. CONCLUSIONS: In this study, male patients reported better outcomes at 1 year after surgery for TLBF than women. Disability strongly correlated with the overall HRQOL, physical and mental health in women, but not in men. We found gender-related differences favoring men after surgical interventions for spinal fractures.

Genetically enhanced T lymphocytes and the intensive care unit.

Chimeric antigen receptor-modified T cells (CAR-T cells) and donor lymphocyte infusion (DLI) are important protocols in lymphocyte engineering. CAR-T cells have emerged as a new modality for cancer immunotherapy due to their potential efficacy against hematological malignancies. These genetically modified receptors contain an antigen-binding moiety, a hinge region, a transmembrane domain, and an intracellular costimulatory domain resulting in lymphocyte T cell activation subsequent to antigen binding. In present-day medicine, four generations of CAR-T cells are described depending on the intracellular signaling domain number of T cell receptors. DLI represents a form of adoptive therapy used after hematopoietic stem cell transplant for its anti-tumor and anti-infectious properties. This article covers the current status of CAR-T cells and DLI research in the intensive care unit (ICU) patient, including the efficacy, toxicity, side effects and treatment.

The role of the pathology department in the preanalytical phase of molecular analyses.

After introducing the new molecules for the treatment of patients with tumoral pathology, the therapeutical decision will be taken depending on the molecular profile performed upon the harvested tissues. This major modification makes the molecular and morphological analysis an essential part in the clinical management of patients and the pathologist plays an important role in this process. The quality and reproducibility of the results are imperative today and they depend on both the reliability of the molecular techniques and the quality of the tissue we use in the process. Also, the genomics and proteomics techniques, used increasingly often, require high-quality tissues, and pathology laboratories play a very significant role in the management of all phases of this process. In this paper the parameters which must be followed in order to obtain optimal results within the techniques which analyze nucleic acids and proteins were reviewed.