Energy window optimization in bremsstrahlung imaging after Yttrium-90 microsphere therapy.

In imaging of Yttrium-90 patients treated hepatic primary and metastatic cancers, bremsstrahlung photons produced in a wide energy range is used. However, the image quality depends on acquisition energy window. This research aimed energy window optimization for Yttrium-90 bremsstrahlung imaging and 48 patients with various types of cancer received radioembolization therapy were investigated. Patients were imaged using a GE Healthcare Optima NM/CT 640 series gamma camera system with a medium energy general-purpose (MEGP) collimator and planar images were acquired with 8 different energy windows in the 55-400 keV energy range. The data set, formed with the % FOV, contrast, and spatial resolution of image quality parameters calculated from these images, was statistically examined with ANOVA and Tukey tests. According to the visual evaluations and ANOVA/Tukey test results, it was statistically concluded that energy window of 90-110 keV is the optimal energy window while 60-400 keV energy ranges show the lowest image quality for Y-90 bremsstrahlung imaging.

The effect of thrombosis-related laboratory values on mortality in COVID-19 infection.

OBJECTIVE: COVID-19 may cause thrombosis in both venous and arterial systems. Familiarity with the signs and symptoms of thrombosis and its treatment is essential in treating COVID-19 infection and its complications. D-Dimer and mean platelet volume (MPV) are measurements related to the development of thrombosis. This study investigates whether MPV and D-Dimer values could be used to determine the risk of thrombosis and mortality in the COVID-19 early stages. PATIENTS AND METHODS: 424 patients who were COVID-19 positive, according to the World Health Organization (WHO) guidelines, were randomly and retrospectively included in the study. Demographic and clinical characteristics such as age, gender, and length of hospitalization were obtained from the digital records of participants. Participants were divided into living and deceased groups. The patients' biochemical, hormonal, and hematological parameters were analyzed retrospectively. RESULTS: White blood cells (WBC), neutrophils, and monocytes were significantly different in the two groups (p-value <0.001), and their values were lower in the living group than in the deceased group. MPV median values did not differ according to prognosis (p-value = 0.994). While the median value was 9.9 in the survivors, it was 10 in the deceased. Creatinine, procalcitonin, ferritin, and the number of hospitalization days in living patients were significantly lower than in patients who died (p-value <0.001). Median values of D-dimer (mg/L) differ according to prognosis (p-value <0.001). While the median value was 0.63 in the survivors, it was found as 438 in the deceased. CONCLUSIONS: Our results did not show any significant relationship between the mortality of COVID-19 patients and their MPV levels. However, a significant association between D-Dimer and mortality in COVID-19 patients was observed.

The significance of a novel inflammatory biomarker, presepsin, in predicting disease prognosis in patients with COVID-19.

OBJECTIVE: This study aims at determining the significance of a novel inflammatory biomarker, presepsin, in predicting disease prognosis in patients with COVID-19. PATIENTS AND METHODS: This retrospective study was concluded at the University Hospital between April and August 2020. The study involved 88 COVID-19 patients (48 men and 40 women). The patients were categorized into two groups: the patients admitted to the COVID-19 clinic, described as the moderate COVID-19 patients (Group-1; n=44), and those admitted to the internal medicine outpatient clinic, who were the mild COVID-19 patients (Group-2; n=44). The groups were compared using inflammatory markers: presepsin, C-Reactive Protein to Albumin Ratio, Neutrophil to Lymphocyte Ratio, and procalcitonin. RESULTS: Serum presepsin levels (195.29 vs. 52.12 pg/ml) were significantly higher in the Group-1 compared to the Group-2 (p=0.001). The gender distribution and average age were similar in both groups (p > 0.05). While ferritin, lactate dehydrogenase, D-Dimer, platelet lymphocyte ratio, C-Reactive Protein to Albumin Ratio (p=0.001), erythrocyte sedimentation ratio, C-Reactive Protein and presepsin were significantly higher in the Group-1 compared to Group-2 (p<0.05), while hemoglobin and lymphocyte were significantly lower in the Group-1 than in Group-2 (p<0.05). CONCLUSIONS: Serum presepsin levels were found to be significantly higher in moderate clinical group COVID-19 patients compared to mild group. Presepsin, a new inflammatory biomarker, may be useful in predicting the prognosis and early treatment of COVID-19 infection.

Interleukin-17E, inducible nitric oxide synthase and arginase1 as new biomarkers in the identification of neutrophilic dermatoses.

BACKGROUND: Neutrophilic dermatoses (ND) are a heterogeneous group of diseases, but can often have a relatively similar histological appearance. AIM: To identify a combination of biomarkers allowing a better differentiation of ND types. METHODS: Biopsies were obtained from normal human skin (NS; n = 4), chronic plaque-type psoriasis (PsO; n = 7), paradoxical psoriasis (PP; n = 8), generalized pustular psoriasis (GPP; n = 9), subcorneal pustular dermatosis of Sneddon-Wilkinson (SPD; n = 3), acute generalized exanthematous pustulosis (AGEP; n = 3), hidradenitis suppurativa (HS; n = 7), Sweet syndrome (SS; n = 8) and pyoderma gangrenosum (PG; n = 8). Samples were analysed by immunofluorescence using three biomarkers, interleukin (IL)-17E, inducible nitric oxide synthase (iNOS) and arginase1, each one in combination with two cell markers, myeloperoxidase (MPO) and CD68, which allow the identification of neutrophils and macrophages, respectively. RESULTS: We found that SS is characterized by high expression of IL-17E and iNOS in the epidermis, while PG exhibits low expression. The density of the neutrophil infiltrate helps to differentiate PP (high-density infiltrate) from PsO (low-density infiltrate). High expression of arginase1 in the granular layer of the epidermis is a hallmark of SPD. Finally, mature neutrophils and proinflammatory macrophages are readily detectable in PP, SPD and PG, whereas immature neutrophils and anti-inflammatory macrophages are more frequent in GPP, AGEP, HS and SS. CONCLUSIONS: The analysis of ND by immunofluorescence using IL-17E, iNOS and arginase1 in combination with MPO and CD68 allows for characterization of differential expression patterns in the epidermis as well as the determination of the polarization status of the dermal neutrophils and macrophages. The appropriate markers may help in the differentiation of ND in clinical practice.

Transcranial Infrared Laser Stimulation for the Treatment of Traumatic Brain Injury: A Case Series.

Introduction: This study intended to evaluate the safety and possible therapeutic effect of transcranial infrared laser stimulation (TILS) based on photobiomodulation (PBM) among patients with traumatic brain injury (TBI). Methods: Eleven participants who were diagnosed with TBI after full neurological examination and MRI evaluation by a board-certified neurologist completed five to eight 20-minute TILS sessions using the Cytonsys CytonPro-5000 apparatus (pilot laser control, focused wavelength of 1064 nm, maximum output power of 10W, maximum optical power density of 500 mW/cm2, effective area 4.5 cm2 in diameter). Per TILS session, participants underwent a laser dose of 250 mW/cm2 continuous laser wave to each hemisphere using predetermined patient-specific coordinates. Structural imaging was used to neuronavigate individual treatment targets in the frontal cortex (Brodmann area 10). The primary safety measure for this study was the occurrence of adverse events (AEs) or serious adverse events (SAEs). The primary efficacy outcome measure was the participant-rated global rating of change (GRC) post-intervention. Secondary outcome measures included a battery of neuropsychological testing and mood questionnaires done both pre- and post-intervention. Results: All patients enrolled in this study protocol were able to tolerate the study procedures without any AEs or SAEs. Nine out of eleven participants had clinically significant improvements in GRC score (≥ +2). Neuropsychological testing and mood questionnaire outcomes also suggested a positive therapeutic effect. Conclusion: This study provides preliminary evidence supporting the safety and potential efficacy of TILS as a non-invasive clinical intervention for individuals with TBI.

Clinicopathological features of cutaneous reactions after mRNA-based COVID-19 vaccines.

BACKGROUND: Cutaneous reactions, mostly on injection site after mRNA-based COVID-19 vaccines, have been reported but not with detailed histopathological characterization. OBJECTIVES: Characterization and classification of these reactions in a clinical and pathological point of view. METHODS: Monocentric case series of 11 patients with cutaneous manifestations, clinically and histologically characterized after COVID-19 vaccination. RESULTS: From January to June 2021, we recorded 11 cutaneous reactions to mRNA COVID-19 vaccines from BNT162b2 (n = 8) and mRNA-1273 (n = 3). Generalized reactions showing erythematous rash or purpura were the most common clinical presentation, and drug-reaction-like pattern was the most common histological finding. CONCLUSIONS: A proper clinicopathological classification will be helpful in the early diagnosis and management of the cutaneous reactions to mRNA COVID-19 vaccines.

Chloracne: a case series on cutaneous expression of CYP1A1 as diagnostic biomarker.

Chloracne, also known as metabolizing acquired dioxin-induced skin hamartomas (MADISH), is a rare disfiguring disease related to dioxin exposure. There is a paucity of literature on the clinical manifestations and pathogenesis of chloracne/MADISH. The aim of this study was to assess the clinical features of this very unusual acneiform eruption and to explore the pathogenesis of the disease. This was a retrospective, observational report study was conducted on five patients belonging to the same nuclear family (father, mother and three children) and a relative (father's brother) living in the same house. Histopathological, immunohistochemical, laboratory and toxicological analyses were performed for all patients. The results suggest that CYP1A1 in human skin is a diagnostic biomarker in chloracne, and was positive for all the patients in our sample. Tetrachlorodibenzo-p-dioxin is the most investigated dioxin responsible for chloracne; however, several other agonists, whether dioxin-like or not, can activate the aryl hydrocarbon receptor. To our knowledge, this Italian case series is the first study to suggest polychlorinated biphenyls as a possible cause of an overstimulation of aryl hydrocarbons causing the consequent acneiform eruption.

Bilateral asymmetry and developmental plasticity of the humerus in modern humans.

OBJECTIVE: This study investigates bilateral asymmetry in the humerus of modern human populations with differing activity patterns to assess the relative plasticity of different bone regions in response to environmental influences, particularly the biomechanical demands of handedness. METHODS: External breadths, cross-sectional properties, and centroid sizes were used to quantify directional and absolute asymmetry of humeral diaphyseal, distal periarticular, and articular regions in six populations with differing subsistence strategies (total n = 244). Geometric section properties were measured using computed tomography at six locations along the distal humerus, while centroid sizes of the distal articular and periarticular regions, as well as eight segments of the diaphysis, were extracted from external landmark data. Bilateral asymmetries were compared between populations and sexes. Each property was also tested for correlation with bilateral asymmetry at 40% of bone length, which has been shown to correlate with handedness. RESULTS: Asymmetry is highest in the diaphysis, but significant through all distal bone regions. Asymmetry increases in the region of the deltoid tuberosity, and progressively declines distally through the shaft and distal periarticular region. Articular asymmetry is higher than periarticular asymmetry, approaching levels seen just proximal to the olecranon fossa, and is weakly but significantly correlated with diaphyseal asymmetry. Hunter-gatherers from Indian Knoll have significantly higher levels of asymmetry than other groups and are more sexually dimorphic, particularly in cross-sectional properties of the diaphysis. CONCLUSIONS: Humeral dimensions throughout the diaphysis, including regions currently used in taxonomic assignments of fossil hominins, likely respond to in vivo use, including population and sex-specific behaviors.

Bullous lichen planus and anti-programmed cell death-1 therapy: Case report and literature review.

BACKGROUND: Cutaneous adverse effects of immunotherapies are being seen with increasing frequency in general practice. While anti-PD1 lichenoid reactions are well known, only a few cases of bullous lichen planus have so far been reported in the medical literature. Herein we described a case of secondary bullous lichen planus associated with nivolumab and we present a systematic review of all anti-P1-induced cases reported in the literature. PATIENTS AND METHODS: Three months after beginning treatment with nivolumab for metastatic clear-cell renal carcinoma, a 68-year-old man presented pruritic purplish papules on his limbs that subsequently became bullous. Clinical-histological correlation led us to a diagnosis of secondary bullous lichen planus induced by nivolumab. Systemic steroids and withdrawal of immunotherapy resulted in clinical improvement. REVIEW OF THE LITERATURE: Our systematic review revealed 20 cases of lichen planus induced by anti-PD1 (nivolumab and pembrolizumab) published between 2016 and 2018, 6 of which were of the bullous form. Treatment and maintenance or discontinuation of anti-PD1 were dependent on severity. DISCUSSION: Bullous lichen planus has been reported only rarely in the context of nivolumab therapy. The timeline for development of cutaneous adverse reactions under anti-PD1 immunotherapy may last weeks or months and regular monitoring is required. Withdrawal of immunotherapy should only be considered where the outcome under systemic corticosteroids is unfavourable.

Neuroprotection against CCl4 induced brain damage with crocin in Wistar rats.

Owing to its lipophilic property, carbon tetrachloride (CCl4) is rapidly absorbed by both the liver and brain. We investigated the protective effects of crocin against brain damage caused by CCl4. Fifty rats were divided into five groups of ten: control, corn oil, crocin, CCl4 and CCl4 + crocin. CCl4 administration decreased glutathione (GSH) and total antioxidant status (TAS) levels, and catalase (CAT) activity, while significant increases were observed in malondialdehyde (MDA) and total oxidant status (TOS) levels and superoxide dismutase (SOD) activity. The cerebral cortex nuclear lamina developed a spongy appearance, neuronal degeneration was observed in the hippocampus, and heterochromatic and pyknotic neurons with increased cytoplasmic eosinophilia were observed in the hippocampus after CCl4 treatment. Because crocin exhibits strong antioxidant properties, crocin treatment increased GSH and TAS levels and CAT activities, and decreased MDA and TOS levels and SOD activity; significant improvements also were observed in histologic architecture. We found that crocin administration nearly eliminated CCl4 induced brain damage by preventing oxidative stress.

A comparison of the effects of Methylprednisolone Acetate, Sodium Hyaluronate and Tenoxicam in the treatment of non-reducing disc displacement of the temporomandibular joint.

BACKGROUND: This clinical study aimed to radiologically and clinically compare the effect of intra-articular injection of methylprednisolone, sodium hyaluronate or tenoxicam following arthrocentesis with that of arthrocentesis alone in patients with non-reducing disc displacement. MATERIAL AND METHODS: A total of 44 patients radiographically diagnosed with non-reducing disc displacement of the temporomandibular joint (TMJ) were randomly divided into four treatment groups, as follows: Group 1, arthrocentesis alone; Group 2, arthrocentesis plus methylprednisolone acetate; Group 3, arthrocentesis plus sodium hyaluronate; Group 4, arthrocentesis plus tenoxicam. Maximum mouth opening (MMO), lateral movement, pain severity and tenderness of TMJ and muscles of mastication on palpation were measured before treatment and at 1 week and 1, 3 and 6 months after treatment. Disc position, presence or absence of disc reduction, level of effusion, joint movement and joint space were also evaluated using magnetic resonance imaging (MRI) before treatment and 6 months after treatment. RESULTS: No significant differences in treatment success were found among the four groups. MRI findings did not vary significantly among the groups, but pre- and post-operative MRI findings varied significantly within all four groups (p<0.001). CONCLUSION: According to the data from this study, it may be concluded that either arthrocentesis alone or arthrocentesis with methylprednisolone acetate or sodium hyaluronate or tenoxicam intra-articular injections are similarly effective and promising methods in the treatment of TMJ with non-reducing disc displacement.

RASopathic comedone-like or cystic lesions induced by vemurafenib: a model of skin lesions similar but not identical to those induced by dioxins MADISH.

BACKGROUND: Patients treated with vemurafenib for metastatic melanoma often develop skin lesions similar to those observed after exposure to dioxin-like compounds. We previously called these lesions MADISH (metabolizing acquired dioxin-induced skin hamartoma) when analysing a case of acute dioxin poisoning. OBJECTIVE: We performed a clinical trial aimed at comparing the skin lesions observed under vemurafenib treatment with MADISH in order to bring to light a possible crosstalk between vemurafenib and dioxin pathways. METHODS: In this case series study, we explored the histological aspect of skin lesions in 10 cases treated with vemurafenib for malignant melanoma. We also analysed the ability of vemurafenib and tyrosine kinase inhibitors to induce dioxin-AhR pathway. RESULTS: All patients had skin lesions diagnosed as 'non-inflammatory acneiform eruption' by dermatologists. These were predominantly facial with notable retroauricular involvement and clinically compatible with chloracne/MADISH when assessed by dioxin expert. Histological analysis showed mostly comedone-like lesions and dermal cysts containing epithelial wall with basal or lateral epithelial projections and lamellar keratinization and alterations of remaining sebaceous glands. The expression of CYP1A1, a gene highly induced following dioxin exposure, was not observed in these lesions. Vemurafenib and the tyrosine kinase inhibitors erlotinib and gefitinib did not induce CYP1A1 activity. DISCUSSION: Although the skin lesions under vemurafenib treatment were morphologically similar to MADISH, the absence of CYP1A1 expression in dermal cysts of patients and the absence of CYP1A1 activation by vemurafenib led us consider that these skin lesions were different from true MADISH and not mediated by a crosstalk of AhR signalling, but rather to a hyperactivation of PI3K-Akt pathway as a consequence of vemurafenib treatment. A strong expression of CYP1A1 in the epithelial wall of dermal cysts must be required, parallel to the morphology of the lesions, to make the diagnosis of MADISH, the hallmark of an exposure to dioxin-like/chloracnegen compounds.

Expression of chemerin in the synovial fluid of patients with temporomandibular joint disorders.

The synovial membrane and fluid are significantly involved in the pathogenesis of temporomandibular joint (TMJ) disorders. This study aimed to investigate the relation between levels of chemerin in the synovial fluid (SF) of patients with TMJ disorder and their relationship. Sixty samples of SF were obtained from patients with an internal derangement (ID) or osteoarthritis (OA). Chemerin in the SF was examined by enzyme-linked immunosorbent assay (ELISA). The results showed greater levels of chemerin in the SF of patients with OA than ID. While chemerin levels were positively correlated with pain scores, they were inversely correlated with MMO. Chemerin levels increased progressively as the disorder stage became more severe. The findings of this study suggest that chemerin in SF may play role as a predisposing factor and may represent a novel potential prognostic biochemical marker in the pathogenesis of TMJ disorders.

Time slicing in 3D momentum imaging of the hydrogen molecular ion photo-fragmentation.

Photo-fragmentation of the hydrogen molecular ion was investigated with 800 nm, 50 fs laser pulses by employing a time slicing 3D imaging technique that enables the simultaneous measurement of all three momentum components which are linearly related with the pixel position and slicing time. This is done for each individual product particle arriving at the detector. This mode of detection allows us to directly measure the three-dimensional fragment momentum vector distribution without having to rely on mathematical reconstruction methods, which additionally require the investigated system to be cylindrically symmetric. We experimentally reconstruct the laser-induced photo-fragmentation of the hydrogen molecular ion. In previous experiments, neutral molecules were used as a target, but in this work, performed with molecular ions, the initial vibrational level populations are well-defined after electron bombardment, which facilitates the interpretation. We show that the employed time-slicing technique allows us to register the fragment momentum distribution that reflects the initial molecular states with greater detail, revealing features that were concealed in the full time-integrated distribution on the detector.

Probing nonadiabatic molecular alignment by spectral modulation.

We investigated molecular alignment wakes of femtosecond laser pulses. Evolution of nonadiabatic molecular alignment in nitrogen gas has been measured via its nonlinear interaction effects with a variably delayed probe pulse. The induced rotational wave packet was mapped as a function of the angular difference between polarization directions of femtosecond pump and probe pulses as well as their relative delay and the plot of the variations of the rotational wave packet, i.e. "quantum carpet", was found to be in good agreement with the calculated angular and temporal dependencies of molecular alignment parameter.

White-light generation control with crossing beams of femtosecond laser pulses.

We investigated the variations in generated white-light when crossing two femtosecond laser beams in a Kerr medium. By changing the relative delay of two interacting intense femtosecond laser pulses, we show that white-light generation can be enhanced or suppressed. With a decrease of the relative delay an enhancement of the white-light output was observed, which at even smaller delays was reverted to a suppression of white-light generation. Under choosen conditions, the level of suppression resulted in a white-light output lower than the initial level corresponding to large delays, when the pulses do not overlap in time. The enhancement of the white-light generation takes place in the pulse that is lagging. We found that the effect of the interaction of the beams depends on their relative orientation of polarization and increases when the polarizations are changed from perpendicular to parallel. The observed effects are explained by noting that at intermediate delays, the perturbations introduced in the path of the lagging beam lead to a shortening of the length of filament formation and enhancement of the white-light generation, whereas at small delays the stronger interaction and mutual rescattering reduces the intensity in the central part of the beams, suppressing filamentation and white-light generation.

Serum leptin in neonatal lambs is associated with temperature, plasma lipids and metabolites.

In this study we investigated changes of serum leptin in 74 newborn lambs and associations with environmental temperature (from - 8°C to + 25°C), body temperature, and concentrations of plasma lipids, 3-beta-hydroxybutyric acid and blood glucose. A leptin radioimmunoassay was established, using an antiserum (rabbit) produced against a partial sequence of ovine leptin (31-44). Before measurement, serum samples were denatured. The sensitivity of the assay was 0.4 µg l(-1) and intra- and interassay coefficients of variation were 5.1% and 2.5%, respectively. Blood samples were collected immediately after birth up to 24 h postnatally (pn). Median leptin concentrations at birth and 24 h pn were 20.9 and 52.7 µg l(-1), respectively. Because of non-normal distribution, leptin concentrations were converted to log(leptin) before further statistical processing. The change in log(leptin) during the first 24 h was highly significant (p<0.0001). Correlation analysis showed significant associations between serum leptin and the following variables: environmental temperature 24 h pn (r=0.34, p<0.005), log(plasma triglycerides) 24 h pn (r=0.50, p<0.001), log(plasma 3-beta-hydroxybutyric acid) 24 h pn (r=-0.50, p<0.001), blood glucose 6 h pn (r=0.43, p<0.001) and plasma cholesterol 12 h pn (r=0.38, p=0.001). We conclude that this radioimmunoassay is suited to measure total serum ovine leptin and that total leptin is already regulated in the very early postnatal phase. Leptin is increased at higher environmental temperatures, consistent with leptin's suppressive effect on energy expenditure and appetite. Furthermore, leptin levels are associated with plasma concentrations of lipids and lipid metabolites.