ABSTRACT
Mesenchymal stromal cell (MSC) apoptosis is required for in vivo immunosuppression. However, the induction of apoptosis is heavily dependent on the recipient's immune system. In graft-versus-host disease (GvHD), patients who fail to respond to MSCs are in fact those whose immune cells are unable to induce MSC apoptosis ex vivo. The information is critical to explain why responses in clinical trials vary even though the same sources of MSC products are infused. More importantly, it highlights the need for an alternative MSC treatment for the nonresponders. By using a mouse model of ovalbumin (OVA)-induced allergic inflammation, we demonstrated that we could generate apoptotic MSCs (ApoMSCs) in vitro and use them to successfully reduce allergic airway inflammation. In order to address the logistics of their potential future clinical application, we have shown that ApoMSCs could be cryopreserved without impairing efficacy compared to freshly generated ApoMSCs. We have also highlighted that MSCs need to undergo complete apoptosis before cryopreservation to retain their immunosuppressive activity. The cryopreserved ApoMSCs could serve as a potential future off-the-shelf cellular product, in particular for patients who suffer from inflammatory conditions yet do not harbor the immune capacity to induce MSC apoptosis in vivo. Our data provide proof-of-concept that under laboratory conditions, ApoMSCs can be successfully frozen and thawed without affecting their anti-inflammatory activity, as tested in a murine model of allergic inflammation.
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Background: Attention deficit hyperactivity disorder (ADHD) is characterized by impairments in developmental-behavioral inhibition, resulting in impulsivity and hyperactivity. Recent research has underscored cortical inhibition deficiencies in ADHD via the gamma-aminobutyric acid (GABA)ergic system, which is crucial for maintaining excitatory-inhibitory balance in the brain. This study explored postnatal changes in parvalbumin (PV) immunoreactivity, indicating GABAergic interneuron types, in the prefrontal (PFC) and motor (MC) cortices of spontaneously hypertensive rats (SHRs), an ADHD animal model. Methods: Examining PV- positive (PV+) cells associated with dopamine D2 receptors (D2) and the impact of dopamine on GABA synthesis, we also investigated changes in the immunoreactivity of D2 and tyrosine hydroxylase (TH). Brain sections from 4- to 10-week-old SHRs and Wistar Kyoto rats (WKYs) were immunohistochemically analyzed, comparing PV+, D2+ cells, and TH+ fiber densities across age-matched SHRs and WKYs in specific PFC/MC regions. Results: The results revealed significantly reduced PV+ cell density in SHRs: prelimbic (~20% less), anterior cingulate (~15% less), primary (~15% less), and secondary motor (~17% less) cortices. PV+ deficits coincided with the upregulation of D2 in prepubertal SHRs and the downregulation of TH predominantly in pubertal/postpubertal SHRs. Conclusion: Reduced PV+ cells in various PFC regions could contribute to inattention/behavioral alterations in ADHD, while MC deficits could manifest as motor hyperactivity. D2 upregulation and TH deficits may impact GABA synthesis, exacerbating behavioral deficits in ADHD. These findings not only shed new light on ADHD pathophysiology but also pave the way for future research endeavors.
ABSTRACT
The amygdala has large populations of neurons utilizing specific calcium-binding proteins such as parvalbumin (PV), calbindin (CB), or calretinin (CR). They are considered specialized subsets of γ-aminobutyric acid (GABA) interneurons; however, many of these cells are devoid of GABA or glutamate decarboxylase. The neurotransmitters used by GABA-immunonegative cells are still unknown, but it is suggested that a part may use glutamate. Thus, this study investigates in the amygdala of the guinea pig relationships between PV, CB, or CR-containing cells and GABA transporter (VGAT) or glutamate transporter type 2 (VGLUT2), markers of GABAergic and glutamatergic neurons, respectively. The results show that although most neurons using PV, CB, and CR co-expressed VGAT, each of these populations also had a fraction of VGLUT2 co-expressing cells. For almost all neurons using PV (~90%) co-expressed VGAT, while ~1.5% of them had VGLUT2. The proportion of neurons using CB and VGAT was smaller than that for PV (~80%), while the percentage of cells with VGLUT2 was larger (~4.5%). Finally, only half of the neurons using CR (~53%) co-expressed VGAT, while ~3.5% of them had VGLUT2. In conclusion, the populations of neurons co-expressing PV, CB, and CR are in the amygdala, primarily GABAergic. However, at least a fraction of neurons in each of them co-express VGLUT2, suggesting that these cells may use glutamate. Moreover, the number of PV-, CB-, and CR-containing neurons that may use glutamate is probably larger as they can utilize VGLUT1 or VGLUT3, which are also present in the amygdala.
Subject(s)
Calcium-Binding Proteins , gamma-Aminobutyric Acid , Guinea Pigs , Animals , Calcium-Binding Proteins/metabolism , Calbindin 2/metabolism , Calbindins/metabolism , gamma-Aminobutyric Acid/metabolism , Parvalbumins/metabolism , Glutamates/metabolism , Amygdala/metabolismABSTRACT
BACKGROUND: Solid pseudopapillary neoplasm (SPN) is an uncommon pathology of the pancreas with unpredictable malignant potential. Endoscopic ultrasound (EUS) assessment plays a vital role in lesion characterization and confirmation of the tissue diagnosis. However, there is a paucity of data regarding the imaging assessment of these lesions. AIM: To determine the characteristic EUS features of SPN and define its role in preoperative assessment. METHODS: This was an international, multicenter, retrospective, observational study of prospective cohorts from 7 large hepatopancreaticobiliary centers. All cases with postoperative histology of SPN were included in the study. Data collected included clinical, biochemical, histological and EUS characteristics. RESULTS: One hundred and six patients with the diagnosis of SPN were included. The mean age was 26 years (range 9 to 70 years), with female predominance (89.6%). The most frequent clinical presentation was abdominal pain (80/106; 75.5%). The mean diameter of the lesion was 53.7 mm (range 15 to 130 mm), with the slight predominant location in the head of the pancreas (44/106; 41.5%). The majority of lesions presented with solid imaging features (59/106; 55.7%) although 33.0% (35/106) had mixed solid/cystic characteristics and 11.3% (12/106) had cystic morphology. Calcification was observed in only 4 (3.8%) cases. Main pancreatic duct dilation was uncommon, evident in only 2 cases (1.9%), whilst common bile duct dilation was observed in 5 (11.3%) cases. One patient demonstrated a double duct sign at presentation. Elastography and Doppler evaluation demonstrated inconsistent appearances with no emergence of a predictable pattern. EUS guided biopsy was performed using three different types of needles: Fine needle aspiration (67/106; 63.2%), fine needle biopsy (37/106; 34.9%), and Sonar Trucut (2/106; 1.9%). The diagnosis was conclusive in 103 (97.2%) cases. Ninety-seven patients were treated surgically (91.5%) and the post-surgical SPN diagnosis was confirmed in all cases. During the 2-year follow-up period, no recurrence was observed. CONCLUSION: SPN presented primarily as a solid lesion on endosonographic assessment. The lesion tended to be located in the head or body of the pancreas. There was no consistent characteristic pattern apparent on either elastography or Doppler assessment. Similarly SPN did not frequently cause stricture of the pancreatic duct or common bile duct. Importantly, we confirmed that EUS-guided biopsy was an efficient and safe diagnostic tool. The needle type used does not appear to have a significant impact on the diagnostic yield. Overall SPN remains a challenging diagnosis based on EUS imaging with no pathognomonic features. EUS guided biopsy remains the gold standard in establishing the diagnosis.
ABSTRACT
The current work focuses on the synthesis of hybrid nanoparticles (NPs) made of a silica core (Si NPs) coated with discrete gold nanoparticles (Au NPs), which exhibit localized surface plasmon resonance (LSPR) properties. This plasmonic effect is directly related to the nanoparticles size and arrangement. In this paper, we explore a wide range of size for the silica cores (80, 150, 400, and 600 nm) and for the gold NPs (8, 10, and 30 nm). Some rational comparison between different functionalization techniques and different synthesis methods for the Au NPs are proposed, related to the optical properties and colloidal stability in time. An optimized, robust and reliable synthesis route is established, which improves the gold density and homogeneity. The performances of these hybrid nanoparticles are evaluated in order to be used in the shape of a dense layer for pollutant detection in gas or liquids, and find numerous applications as a cheap and new optical device.
ABSTRACT
To re-examine the paradoxical effect hypothesis of abused drugs, the present study concerned whether different doses of morphine disparately affect neuronal activity and associations among the subareas of the medial prefrontal cortex (mPFC: cingulate cortex 1-Cg1, prelimbic cortex-PrL, infralimbic cortex-IL), the subregions of the nucleus accumbens (NAc; both core and shell), and the basolateral amygdala (BLA) following conditioned taste aversion (CTA) and conditioned place preference (CPP). All rats were given a 0.1% saccharin solution for 15-min, and they were intraperitoneally injected with saline or 20, 30, or 40 mg/kg morphine to form the aversive CTA learning. Later, half of the rats were tested for CPP (including the CTA and then CPP tests) for 30-min. Finally, the immunohistochemical staining with c-Fos was conducted after the behavioral test. After the CTA test, c-Fos (%) in the Cg1 and PrL (but not the IL) was more in 20-40 mg/kg of the morphine groups; c-Fos (%) in the NAc core, NAc shell, and BLA was more in the 30-40 mg/kg morphine group. After the CPP test, the Cg1, PrL, IL, and BLA showed more c-Fos (%) in 20 mg/kg morphine; the NAc core showed fewer in c-Fos (%) in the 30-40 mg/kg morphine groups. The mPFC subregions (e.g., Cg1, PrL, and IL), NAc subareas (e.g., NAc core and NAc shell), and BLA were involved in the different doses of morphine injections. The correlation analysis showed that a positive correlation was observed between PrL and IL with NAc core with low doses of morphine and with NAc shell with increasing doses of morphine after the CTA test. After the CPP, an association between PrL and NAc core and NAc shell at low doses and between IL and BLA and NAc shell with increasing doses of morphine. Therefore, different neural substrates and the neural connectivity are observed following different doses of morphine and after the CTA and CPP tests. The present data extend the paradoxical effect hypothesis of abused drugs.
ABSTRACT
The amygdala is modulated by dopaminergic and cholinergic neurotransmission, and this modulation is altered in mood disorders. Therefore, this study was designed to evaluate the presence/absence of quantitative alterations in the expression of main dopaminergic and cholinergic markers in the amygdala of mice with oestrogen receptor ß (ERß) knock-out which exhibit increased anxiety, using immunohistochemistry and quantitative methods. Such alterations could either contribute to increased anxiety or be a compensatory mechanism for reducing anxiety. The results show that among dopaminergic markers, the expression of tyrosine hydroxylase (TH), dopamine transporter (DAT) and dopamine D2-like receptor (DA2) is significantly elevated in the amygdala of mice with ERß deprivation when compared to matched controls, whereas the content of dopamine D1-like receptor (DA1) is not altered by ERß knock-out. In the case of cholinergic markers, muscarinic acetylcholine type 1 receptor (AChRM1) and alpha-7 nicotinic acetylcholine receptor (AChRα7) display overexpression while the content of acetylcholinesterase (AChE) and vesicular acetylcholine transporter (VAChT) remains unchanged. In conclusion, in the amygdala of ERß knock-out female the dopaminergic and cholinergic signalling is altered, however, to determine the exact role of ERß in the anxiety-related behaviour further studies are required.
Subject(s)
Dopamine , Estrogen Receptor beta , Mice , Female , Animals , Dopamine/metabolism , Estrogen Receptor beta/genetics , Estrogen Receptor beta/metabolism , Acetylcholinesterase/metabolism , Amygdala/metabolism , Receptors, Muscarinic/genetics , Receptors, Muscarinic/metabolism , Cholinergic Agents/metabolismABSTRACT
The mammalian preoptic area (POA) has large populations of calbindin (CB), calretinin (CR) and parvalbumin (PV) neurons, but phenotypes of these cells are unknown. Therefore, the question is whether neurons expressing CB, CR, and/or PV are GABAergic or glutamatergic. Double-immunofluorescence staining followed by epifluorescence and confocal microscopy was used to determine the coexpression patterns of CB, CR and PV expressing neurons with vesicular GABA transporters (VGAT) as specific markers of GABAergic neurons and vesicular glutamate transporters (VGLUT 2) as specific markers of glutamatergic neurons. The guinea pig was adopted as, like humans, it has a reproductive cycle with a true luteal phase and a long gestation period. The results demonstrated that in the guinea pig POA of both sexes, ~80% of CB+ and ~90% of CR+ neurons coexpress VGAT; however, one-fifth of CB+ neurons and one-third of CR+ cells coexpress VGLUT. About two-thirds of PV+ neurons express VGAT, and similar proportion of them coexpress VGLUT. Thus, many CB+, CR+ and PV+ neurons may be exclusively GABAergic (VGAT-expressing cells) or glutamatergic (VGLUT-expressing cells); however, at least a small fraction of CR+ cells and at least one-third of PV+ cells are likely neurons with a dual GABA/glutamate phenotype that may coexpress both transporters.
Subject(s)
Calcium-Binding Proteins , Preoptic Area , Animals , Calbindin 2/metabolism , Calbindins/metabolism , Calcium-Binding Proteins/metabolism , Female , GABAergic Neurons/metabolism , Guinea Pigs , Humans , Male , Mammals/metabolism , Parvalbumins/metabolism , Phenotype , Preoptic Area/metabolismABSTRACT
Bckground and Objectives: EUS-guided cystogastrostomy is a well-established advanced endoscopic technique with a steep-learning curve which necessitates an ex-vivo simulator that would allow for adequate training. The aim of this study is to evaluate the feasibility of the model in allowing training for EUS-guided cystogastrostomy using lumen-apposing metal stent (LAMS). Subjects and Methods: The model was created by ROEYA Training Center, Egypt, using native porcine tissue to create fluid collections simulating both cystic and solid lesions. It was designed and tested in advance while the hydrogel was added on-site. The simulator was evaluated prospectively in five training sessions involving 17 international experts. The task was to successfully deploy the LAMS to drain the created cyst. After using the simulator, the experts were asked to fill a questionnaire to assess their experience. The primary endpoint was overall satisfaction with the model as a training tool. Results: All of the experts were satisfied with the model as a tool to train endoscopists for the technique. 76.5% (n = 11) of the experts thought the model to be moderately realistic. Proper visualization was reported by 94.1% of the experts. All experts believed the lesions to be either slightly like or very similar to real lesions. The model was graded "easy" in difficulty by 11 of the experts. Conclusions: In all parameters assessed, the experts thought the model to be a useful tool for future training. This preliminary study suggests that the aforementioned simulator can be used to train endoscopists on using LAMS in a risk-free environment.
ABSTRACT
Acute myeloid leukemia (AML) accounts for approximately 15-20% of all childhood leukemia cases. The overall survival of children with acute myeloid leukemia does not exceed 82%, and the 5-year event-free survival rates range from 46% to 69%. Such suboptimal outcomes are the result of numerous mutations and epigenetic changes occurring in this disease that adversely affect the susceptibility to treatment and relapse rate. We describe various molecular-targeted therapies that have been developed in recent years to meet these challenges and were or are currently being studied in clinical trials. First introduced in adult AML, novel forms of treatment are slowly beginning to change the therapeutic approach to pediatric AML. Despite promising results of clinical trials investigating new drugs, further clinical studies involving greater numbers of pediatric patients are still needed to improve the outcomes in childhood AML.
Subject(s)
Leukemia, Myeloid, Acute , Child , Epigenesis, Genetic , Humans , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Molecular Targeted Therapy , Mutation , RecurrenceABSTRACT
Oestrogen receptor ß (ERß) knock-out female mice display increased anxiety and decreased threshold for synaptic plasticity induction in the basolateral amygdala. This may suggest that the γ-aminobutyric acid (GABA) inhibitory system is altered. Therefore, the immunoreactivity of main GABAergic markers-i.e., calbindin, parvalbumin, calretinin, somatostatin, α1 subunit-containing GABAA receptor and vesicular GABA transporter-were compared in the six subregions (LA, BL, BM, ME, CE and CO) of the amygdala of adult female wild-type and ERß knock-out mice using immunohistochemistry and quantitative methods. The influence of ERß knock-out on neuronal loss and glia was also elucidated using pan-neuronal and astrocyte markers. The results show severe neuronal deficits in all main amygdala regions in ERß knock-out mice accompanied by astroglia overexpression only in the medial, basomedial and cortical nuclei and a decrease in calbindin-expressing neurons (CB+) in the amygdala in ERß knock-out mice compared with controls, while other markers of the GABAergic system remain unchanged. Concluding, the lack of ERß led to failure in the structural integrity of the CB+ subpopulation, reducing interneuron firing and resulting in a disinhibitory effect over pyramidal function. This fear-promoting excitatory/inhibitory alteration may lead to the increased anxiety observed in these mice. The impact of neuronal deficits and astroglia overexpression on the amygdala functions remains unknown.
ABSTRACT
The aim of the current study was to assess the influence of embryonic exposure to cadmium on basic and derived erythrocyte indices, the morphology and morphometric properties of erythrocytes, as well as erythrocyte spectrin distribution in newly hatched Gallus gallus domesticus chicks. The eggs were injected with cadmium (Cd) at a dose of 2 µg, 4 µg, 6 µg, or 8 µg per egg on the sixth day of incubation. Blood samples were collected on the first day after hatching. Exposure to cadmium resulted in higher levels of red blood cell count, hemoglobin concentration, and hematocrit value, while derived erythrocyte indices were lower (mean corpuscular volume) or higher (mean corpuscular hemoglobin concentration) in comparison to the control. These changes occurred in animals exposed to higher doses of this toxic agent. In cadmium-treated individuals (2 and 8 µg of Cd), the percentage of erythrocytes which exhibited changed shape increased. Increases in the length (6 and 8 µg) and width (2, 6, and 8 µg) of erythrocytes and the length and width of the nucleus (2-8 µg) of red blood cells were observed. Changes in spectrin distribution were also observed, which indicate alterations at structural and molecular levels.
Subject(s)
Chickens , Erythrocyte Indices , Animals , Cadmium/toxicity , Erythrocyte Indices/veterinary , Erythrocytes , Ovum , Spectrin/pharmacologyABSTRACT
AIM: To assess the association between discharge policy and hospital stay length, and to evaluate the factors related to duration of viral clearance among patients with coronavirus disease 2019 (COVID-19). METHODS: This cross-sectional study enrolled consecutive patients aged ≥18 years with SARS-CoV-2 infection confirmed by reverse transcription polymerase chain reaction test who were admitted to hospital. The participants were divided into the test-based (TB) policy group or symptom-based (SB) group depending on the policy valid at their hospital discharge. Multivariable analyses were performed to assess the factors related to the duration of hospital stay and viral clearance. RESULTS: The study involved 305 patients (66.6% men). The mean age was 60.9 (15.2) years. TB and SB policy groups consisted of 145 (47.5%) and 160 patients (52.5%), respectively. The TB group had significantly longer duration of hospital stay (21.0 vs 16.0, P=0.003). In multivariable analysis, SB policy was associated with significantly shorter hospital stay (ß-coefficient -5.87, 95% confidence interval [CI] -9.78 to -1.96, P=0.003). Longer viral clearance was associated with older age (ß-coefficient 0.33, 95% CI 0.15 to 0.51, P<0.001) and history of cough in the pre-hospital phase of the disease (5.96, 95% CI 0.64 to 11.29, P = 0.028). CONCLUSION: SB discharge policy is preferable in the context of limited resources during the COVID-19 pandemic.
Subject(s)
COVID-19 , Adolescent , Adult , COVID-19/epidemiology , Cross-Sectional Studies , Female , Humans , Length of Stay , Male , Middle Aged , Pandemics , Patient Discharge , Policy , Retrospective Studies , SARS-CoV-2ABSTRACT
The amygdala primarily evolved as a danger detector that regulates emotional behaviours and learning. However, it is also engaged in stress responses as well as olfactory/pheromonal and reproductive functions. All of these functions are processed by a set of nuclei which are derived from different telencephalic sources (pallial and subpallial) and have a unique cellular structure and specific connections. It is unclear how these individual anatomical and functional units evolved to fit the amygdala to the specific needs of various mammals. Thus, this study provides quantitative data regarding volumes, neuron density and neuron numbers in the main amygdala nuclei of the common shrew, guinea pig, rabbit, fox and pig - species from across the mammalian phylogeny which differ in brain complexity and ecology. The results show that the volume of the amygdala and its individual nuclei scale with negative allometry relative to brain mass (an allometric coefficient below one). However, in relation to the whole amygdala volume, volumes and volumetric percentages of the lateral (LA) and basomedial (BM) nuclei scale with positive allometry, for the medial (ME) and lateral olfactory tract (NLOT) nuclei these parameters scale with negative allometry while the values of these parameters for the basolateral (BL), central (CE) and cortical (CO) nuclei scale with isometry. Moreover, density of neurons scales with strong negative allometry relative to both brain mass and amygdala volume with values of allometric coefficient below zero across studied species. This value for BL is significantly lower than that for the whole amygdala, for ME it is significantly higher while values for NLOT, CE, CO, LA and BM are quite similar to the value for whole amygdala. Finally, neuron numbers in the whole amygdala and its individual nuclei scale with negative allometry in relation to brain mass. However, in relation to the number of neurons in the whole amygdala, neuron numbers and percentages of neurons for LA and BM scale with positive allometry, for BL and NLOT they scale with negative allometry while the values of these parameters for CE, CO and ME scale with isometry. In conclusion, all of these results indicate that each of the nuclei studied displays a different and unique pattern of evolution in relation to brain mass or the whole amygdala volume. These patterns do not match with the various classical concepts of amygdala parcellation; however, in some way, they reflect diversity revealed by the expression of homeobox genes in various embryological studies.
Subject(s)
Amygdala/anatomy & histology , Neural Pathways , Neurons , Animals , Foxes , Guinea Pigs , Neural Pathways/physiology , Neurons/cytology , Rabbits , Shrews , SwineABSTRACT
BACKGROUND AND AIM: The proper visibility of mucosa during esophagogastroduodenoscopy (EGD) is crucial for the detection of early upper gastrointestinal tract lesions. In contrast to colonoscopy, no validated scoring system for the assessment of upper gastrointestinal mucosal cleanliness has been developed so far. The aim of the study was to create and validate standardized grading system (POLPREP) to assess the mucosal cleanliness during EGD. METHODS: To assess the visibility of mucosa during EGD, 4-point scale was developed (0-3). Twelve operators assessed 18 images of esophagus, stomach, and duodenum twice (in 2 weeks interval). In validation round, the images and endoscopy reports of 443 EGDs performed in six centers were assessed. RESULTS: The inter-observer accordance of POLPREP was 0.8 (intra-class correlation coefficient; 0.79 consultants, 0.85 trainees). The intra-observer repeatability was 0.64 (Fleiss kappa value; 0.64 consultants, 0.64 trainees). The lesions detection rate was significantly higher in clean (scores 2 and 3; 19.7%) than in "unclean" segments (score 1; 7.7%, P = 0.049). Score 3 was associated with over three-fold higher lesion detection than score 1 (odds ratio 3.2, 95% confidence interval 1.1-9; P = 0.03). CONCLUSIONS: The proposed POLPREP scale allows for unified assessment of upper gastrointestinal tract mucosal cleanliness. The higher cleanliness scores are related with greater upper gastrointestinal pathologies detection.
Subject(s)
Gastrointestinal Neoplasms , Upper Gastrointestinal Tract , Endoscopy, Digestive System , Gastrointestinal Neoplasms/diagnostic imaging , Humans , Mucous Membrane/diagnostic imaging , Observer Variation , Upper Gastrointestinal Tract/diagnostic imagingABSTRACT
A growing body of studies has recently shown that abused drugs could simultaneously induce the paradoxical effect in reward and aversion to influence drug addiction. However, whether morphine induces reward and aversion, and which neural substrates are involved in morphine's reward and aversion remains unclear. The present study first examined which doses of morphine can simultaneously produce reward in conditioned place preference (CPP) and aversion in conditioned taste aversion (CTA) in rats. Furthermore, the aversive dose of morphine was determined. Moreover, using the aversive dose of 10 mg/kg morphine tested plasma corticosterone (CORT) levels and examined which neural substrates were involved in the aversive morphine-induced CTA on conditioning, extinction, and reinstatement. Further, we analyzed c-Fos and p-ERK expression to demonstrate the paradoxical effect-reward and aversion and nonhomeostasis or disturbance by morphine-induced CTA. The results showed that a dose of more than 20 mg/kg morphine simultaneously induced reward in CPP and aversion in CTA. A dose of 10 mg/kg morphine only induced the aversive CTA, and it produced higher plasma CORT levels in conditioning and reacquisition but not extinction. High plasma CORT secretions by 10 mg/kg morphine-induced CTA most likely resulted from stress-related aversion but were not a rewarding property of morphine. For assessments of c-Fos and p-ERK expression, the cingulate cortex 1 (Cg1), prelimbic cortex (PrL), infralimbic cortex (IL), basolateral amygdala (BLA), nucleus accumbens (NAc), and dentate gyrus (DG) were involved in the morphine-induced CTA, and resulted from the aversive effect of morphine on conditioning and reinstatement. The c-Fos data showed fewer neural substrates (e.g., PrL, IL, and LH) on extinction to be hyperactive. In the context of previous drug addiction data, the evidence suggests that morphine injections may induce hyperactivity in many neural substrates, which mediate reward and/or aversion due to disturbance and nonhomeostasis in the brain. The results support the paradoxical effect hypothesis of abused drugs. Insight from the findings could be used in the clinical treatment of drug addiction.
ABSTRACT
Background and Objectives: GISTs (Gastrointestinal stromal tumors) are the most common mesenchymal gastrointestinal tract tumours and are mainly located in the stomach. Their malignant potential depends on size, location, and type. Endoscopic techniques are a less invasive modality for patients not eligible for surgery. ESD (endoscopic submucosal dissection) is mainly used for the removal of smaller GISTs, with intraluminal growth and a more superficial location. Thus, R0 resection capability in some cases may be not sufficient, limited by tumour size, location in the gastric wall, and its connection level with the muscularis propria. In such cases, an endoscopic full-thickness resection can become a new alternative. In this retrospective pilot study, we evaluated ESD and hybrid resection techniques in terms of safety, efficacy, and disease recurrence for selected types of gastric GISTs. Materials and Methods: A retrospective comparison was conducted in a group of patients who underwent ESD or a hybrid technique combining endoscopic resection with endoscopic suturing using the OverStitch system (HT) for type II or III gastric GISTs. A total of 21 patients aged 70 ± 8 years underwent endoscopic resection. Seventeen lesions were treated with ESD and four with the HT. Results: R0 resection was achieved in all patients treated using HT (type III lesions) and in 53% of those treated with ESD (p = 0.08). None of the type III lesions treated with ESD were excised with R0. Lesions treated with R0 ESD resections were significantly smaller (1.76 ± 0.35 cm) than those with R1 ESD resections (2.39 ± 0.40 cm) (p < 0.01). The mean lesion size treated with the HT was 2.88 ± 0.85 cm. Conclusions: HT may be a new resection modality for large gastric GISTs with high muscularis propria connection grades. Further studies are required to evaluate its safety and efficacy and to form precise inclusion criteria for endoscopic resection techniques.
Subject(s)
Gastrointestinal Stromal Tumors , Stomach Neoplasms , Gastrointestinal Stromal Tumors/surgery , Gastroscopy , Humans , Neoplasm Recurrence, Local , Pilot Projects , Retrospective Studies , Stomach Neoplasms/surgery , Treatment OutcomeABSTRACT
INTRODUCTION: The coronavirus disease 2019 (COVID-19) is one of the greatest clinical challenges of the last decades. Clinical factors associated with severity of the disease remain unclear. The aim of the study was to characterize Polish patients hospitalized due to COVID-19 and to evaluate potential prognostic factors of severe course of the disease. MATERIAL AND METHODS: An observational study was conducted from March to July 2020 in the Pulmonology and Allergology Department of the University Hospital in Kraków, Poland. Consecutive patients with confirmed SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection were enrolled, and data about past medical history, signs and symptoms, laboratory results, imaging studies results, in-hospital management and outcomes was prospectively gathered. RESULTS: The study sample comprised 100 patients at the mean age of 59.2 (SD 16.1) years among whom 63 (63.0%) were male. Among them 10 (10.0%) died, 47 (47%) presented respiratory failure, 15 (15.0%) were transferred to the intensive care unit, 17 (17.0%) developed acute kidney injury, 7 (7.0%) had sepsis and 10 (10.0%) were diagnosed with pulmonary embolism. Multivariable analysis revealed age (OR 1.1; 95% CI 1.01-1.15), body mass index (BMI; OR 1.24; 95% CI 1.01-1.53), modified early warning score (MEWS; OR 3.95; 95% CI 1.48-12), the highest d-dimer value (OR 1.73; 95% CI 1.03-2.9) and lactate dehydrogenase (LDH; OR 1.16; 95% CI 1.03-1.3) to be associated with severe course of COVID-19. CONCLUSION: This observational study showed that almost half of hospitalized patients with COVID-19 developed respiratory failure in the course of the disease. Increasing age, BMI, MEWS, d-dimer value and LDH concentration were associated with the severity of COVID-19.
Subject(s)
COVID-19/epidemiology , Hospitalization/statistics & numerical data , Respiratory Insufficiency/epidemiology , Severity of Illness Index , Adult , Age Factors , Aged , COVID-19/therapy , Comorbidity , Female , Humans , Intensive Care Units/statistics & numerical data , Length of Stay , Male , Middle Aged , Obesity/epidemiology , Poland , Respiratory Insufficiency/therapy , Risk FactorsABSTRACT
Biochars produced during biodegradable waste pyrolysis are products with a wide range of environmental applications. The effect of impact biochars depends on their properties which determine the course of specific processes. The main aim of the study was to investigate the effect of pyrolysis temperature on selected properties of biochar produced from various plant wastes (beech wood chips, walnut shells, wheat-rye straw), the valorization of which is of key importance for the implementation of the circular economy. Biochars were produced at temperatures of: 400 °C, 500 °C, 600 °C and 700 °C in a nitrogen atmosphere. An increase in the pyrolysis temperature caused a drop in the biochar production yield. As the temperature increased, higher carbon content and lower hydrogen content could be seen in the products obtained. An increase in the pH and total organic carbon (TOC) values also found. The influence of temperature on ash content, observed in the case of BWS (biochar from walnut shell) and BWRS (biochar from wheat and rye straw), did not occur in the case of BWC (biochar from beech wood chips). Another parameter that demonstrated a growing tendency with increasing temperature was the BET specific surface area (except for biochars from wheat and rye straw). An increase in pyrolysis temperature caused a decrease in the diversity and density of the surface functional groups of biochars. The influence of the type of precursor used in the production of biochar on the presence of surface functional groups was demonstrated. The presence of intense stretching vibrations of C-O bonds, having a potential impact on the sorption capacity of biochars, was determined in the FTIR spectra of BWC600 and BWC700 biochars, this feature, combined with the large BET surface area, may affect the sorption potential of these biochars. The presence of this type of high-intensity vibrations was also observed in the spectra of biochar BWRS600 and BWRS700. This can compensate for the low BET surface value and play an important role when using these biochars in sorption processes for organic and inorganic compounds.