First-dose mRNA vaccination is sufficient to reactivate immunological memory to SARS-CoV-2 in subjects who have recovered from COVID-19

The characterization of the adaptive immune response to COVID-19 vaccination in individuals who recovered from SARS-CoV-2 infection may define current and future clinical practice. To determine the effect of the 2-dose BNT162b2 mRNA COVID-19 vaccination schedule in individuals who recovered from COVID-19 (COVID-19–recovered subjects) compared with naive subjects, we evaluated SARS-CoV-2 Spike–specific T and B cell responses, as well as specific IgA, IgG, IgM, and neutralizing antibodies titers in 22 individuals who received the BNT162b2 mRNA COVID-19 vaccine, 11 of whom had a previous history of SARS-CoV-2 infection. Evaluations were performed before vaccination and then weekly until 7 days after second injection. Data obtained clearly showed that one vaccine dose is sufficient to increase both cellular and humoral immune response in COVID-19–recovered subjects without any additional improvement after the second dose. On the contrary, the second dose proved mandatory in naive subjects to further enhance the immune response. These findings were further confirmed at the serological level in a larger cohort of naive (n = 68) and COVID-19–recovered (n = 29) subjects, tested up to 50 days after vaccination. These results question whether a second vaccine injection in COVID-19–recovered subjects is required, and indicate that millions of vaccine doses may be redirected to naive individuals, thus shortening the time to reach herd immunity.     

Extracting Fuzzy Classification Rules from Texture Segmented HRCT Lung Images

Automatic tools for detection and identification of lung and lesion from high-resolution CT (HRCT) are becoming increasingly important both for diagnosis and for delivering high-precision radiation therapy. However, development of robust and interpretable classifiers still presents a challenge especially in case of non-small cell lung carcinoma (NSCLC) patients. In this paper, we have attempted to devise such a classifier by extracting fuzzy rules from texture segmented regions from HRCT images of NSCLC patients. A fuzzy inference system (FIS) has been constructed starting from a feature extraction procedure applied on overlapping regions from the same organs and deriving simple if–then rules so that more linguistically interpretable decisions can be implemented. The proposed method has been tested on 138 regions extracted from CT scan images acquired from patients with lung cancer. Assuming two classes of tissues C1 (healthy tissues) and C2 (lesion) as negative and positive, respectively; preliminary results report an AUC = 0.98 for lesions and AUC = 0.93 for healthy tissue, with an optimal operating condition related to sensitivity = 0.96, and specificity = 0.98 for lesions and sensitivity 0.99, and specificity = 0.94 for healthy tissue. Finally, the following results have been obtained: false-negative rate (FNR) = 6 % (C1), FNR = 2 % (C2), false-positive rate (FPR) = 4 % (C1), FPR = 3 % (C2), true-positive rate (TPR) = 94 %, (C1) and TPR = 98 % (C2).     

Roquin Paralogs 1 and 2 Redundantly Repress the Icos and Ox40 Costimulator mRNAs and Control Follicular Helper T Cell Differentiation

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Highlights? Ox40 is a target of Roquin-1 and Roquin-2 ? In Rc3h1-2-deficient cells the derepression of Ox40 activates NF-κB and Irf4 ? Roquin-1 and Roquin-2 control inappropriate T cell activation and Tfh differentiation ? Combined loss of Rc3h1 and Rc3h2 imposes Tfh differentiation on CD4 T cells     

Benign Giant Cell Tumour of Tendon Sheaths in a European Lynx (Lynx lynx)

The histological, histochemical, immunohistochemical and ultrastructural features of a benign giant cell tumour (BGCT) of tendon sheaths in a 12‐year‐old male European lynx (Lynx lynx) are reported herein. The neoplastic mass involved the subcutaneous and inter‐muscular tissues of the first, second, third and fourth digit of the left forelimb, from the phalanxes up to the carpus. The tumour appeared as a grey‐whitish tissue mottled with darker areas, along with several scattered foci of orange colour. Histologically, the lesion consisted of a mixed population of numerous, multinucleated giant cells and epithelioid or spindle‐shaped mononuclear cells embedded in a loose, highly vascular stroma. Neoplastic cells lined cleft formations and synovial‐like projections into cystic spaces. No osteoid matrix could be detected. Haemorrhage and necrosis were also observed. The mononuclear and the giant cells were tartrate‐resistant acid phosphatase and periodic acid‐Schiff positive, being also immunohistochemically reactive for lysozyme and vimentin, with a few cells showing immunopositivity also for α‐1‐antitrypsin. Ultrastructurally, histiocyte‐like cells, fibroblast‐like cells and multinucleated giant cells were observed, but no virus‐like particles could be detected in any of the above cell types. The BGCT of tendon sheaths, a fairly uncommon neoplasm in animals, has not been previously reported in the lynx.     

Short- and long-term consequences of prenatal exposure to the cannabinoid agonist WIN55,212-2 on rat glutamate transmission and cognitive functions

The aim of the present review is to summarize integrated neurochemical, morphological and neurobehavioral evidence, in particular from our laboratory, which emphasize the short- and long-term consequences of prenatal exposure to the cannabinoid receptor agonist WIN55,212-2 on rat glutamate transmission and cognitive functions. The results obtained provide evidence that maternal exposure to WIN55,212-2 induces an impairment of cognitive capacities in the offspring. This impairment is associated with alterations of cortical and hippocampal glutamate outflow, cortical neuron morphology and hippocampal long-term potentiation. These findings are in line with clinical data showing that the consumption of marijuana by women during pregnancy has negative consequences on the cognitive functions of their children. Thus, although it is difficult and sometimes misleading to extrapolate findings obtained from animal models to humans, the possibility that an alteration of glutamate transmission might underlie, at least in part, some of the cognitive deficits affecting the offspring of marijuana users, is supported.     

Multiple ovarian cysts in a young girl with severe hypothyroidism.

Case study of a young female patient with severe hypothyroidism due to autoimmune thyroiditis and multiple ovarian cysts is reported. A 14-year 7-month-old girl presented with pelvic and abdominal pain and severe asthenia. Her last menstrual period was 10 months before presentation. Physical examination showed obesity; apathetic and flat expression; periorbital puffiness; pale, cold, dry skin and slow sustained reflexes; swelling in the hands and feet; no galactorrhea; a hardly palpable thyroid gland; and ovaries with a palpable irregular surface. Her heart rate was 90 bpm with a blood pressure within the normal range (110/70 mmHg). Laboratory findings showed severe hypothyroidism (thyroid-stimulating hormone [TSH]: 960 mIU/L), gravis macrocytic anemia, hyperfibrinogenemia, and hyperprolactinemia. Imaging examinations revealed a normal-size thyroid with irregular echogenicity, strongly hypoechogenous area at the neck ultrasonography, bilateral multilocular ovarian masses with cystic components at pelvic ultrasound and computed tomography, and both anterior and posterior pericardial effusion at echocardiography. As soon as thyroid replacement therapy was initiated, all symptoms progressively disappeared and biochemical and hormonal values normalized, while the right ovary did not decrease in size during the follow-up period. For this reason, our patient underwent right ovarian wedge resection 14 months after the initiation of medication replacement. Ovarian histological examination showed a benign ovarian cyst with extensive hemorrhage and myxedematous infiltration. It is concluded that it is important to recognize early in young girls the association between large multiple ovarian cysts and high elevated levels of TSH in order to resolve this disorder with substitutive therapy.     

Mutations in the Insulin‐Like Factor 3 Receptor Are Associated With Osteoporosis

Introduction : Insulin‐like factor 3 (INSL3) is produced primarily by testicular Leydig cells. It acts by binding to its specific G protein–coupled receptor RXFP2 (relaxin family peptide 2) and is involved in testicular descent during fetal development. The physiological role of INSL3 in adults is not known, although substantial INSL3 circulating levels are present. The aim of this study was to verify whether reduced INSL3 activity could cause or contribute to some signs of hypogonadism, such as reduced BMD, currently attributed to testosterone deficiency. Materials and Methods : Extensive clinical, biochemical, and hormonal study, including bone densitometry by DXA, was performed on 25 young men (age, 27–41 yr) with the well‐characterized T222P mutation in the RXFP2 gene. Expression analysis of INSL3 and RXFP2 on human bone biopsy and human and mouse osteoblast cell cultures was performed by RT‐PCR, quantitative RT‐PCR, and immunohistochemistry. Real‐time cAMP imaging analysis and proliferation assay under the stimulus of INSL3 was performed on these cells. Lumbar spine and femoral bone of Rxfp2‐deficient mice were studied by static and dynamic histomorphometry and μCT, respectively. Results : Sixteen of 25 (64%) young men with RXFP2 mutations had significantly reduced BMD. No other apparent cause of osteoporosis was evident in these subjects, whose testosterone levels and gonadal function were normal. Expression analyses showed the presence of RXFP2 in human and mouse osteoblasts. Stimulation of these cells with INSL3 produced a dose‐ and time‐dependent increase in cAMP and cell proliferation, confirming the functionality of the RXFP2/INSL3 receptor–ligand complex. Consistent with the human phenotype, bone histomorphometric and μCT analyses of Rxfp2^?/? mice showed decreased bone mass, mineralizing surface, bone formation, and osteoclast surface compared with wildtype littermates. Conclusions : This study suggests for the first time a role for INSL3/RXFP2 signaling in bone metabolism and links RXFP2 gene mutations with human osteoporosis.     

Knowledge,practice and faith on Total Quality Management principles among workers in the Health Care System: Evidence from an Italian investigation

Background The implementation of Total Quality Management (TQM) principles in the sanitary field, in order to be effective, requires a radical change in management practice as well as the organizational culture and its philosophy. The need to monitor such a transformation emerges too. Objectives This study surveys how well TQM principles are known and understood by health care professionals from the employees' point of view and the factors affecting it. Research design and subjects The Health Care System in Trieste was surveyed. Measures The Total Quality Test was used, a novel and quick instrument aimed at routine assessment of the penetration and interiorization of TQM principles within the health care structure. Results Direct exposure to public, job role and time spent working within the same structure have been proved related to the penetration of TQM principles, whereas previous formative intervention did not prove to be associated with the penetration of TQM principles. Conclusions The implementation of a quick and simple instrument to monitor the TQM implementation highlighted several critical areas for intervention.     

Saporin 6 conjugated to monoclonal antibody selectively kills human melanoma cells.

A novel human melanoma specific immunotoxin is described, which has been produced utilizing the murine monoclonal antibody (mAb) Ep2, IgG2a isotype, recognizing an epitope of the glycoprotein/proteoglycan high molecular weight-melanoma associated antigen. mAb Ep2 has been chemically conjugated by a disulphide bond, using the bifunctional reagent SPDP, to the plant toxin Saporin 6 (SAP) extracted from seeds of Saponaria officinalis. Cytotoxicity studies performed in vitro on melanoma cells have shown that Ep2/SAP immunotoxin efficiently kills antigen expressing cells and that its IC50 is approximately 1 x 10(-10) M, while not affecting the viability of antigen-negative melanoma cells at doses as high as 1 x 10(-7) M, therefore indicating a therapeutic index of Ep2/SAP immunotoxin higher than 1000. Kinetic studies have demonstrated that protein synthesis inhibition by Ep2/SAP is rapidly achieved, since a 90% reduction is observed within 3.1 h, and that this inhibitory activity is apparently first order with time. Furthermore, the cytotoxic activity of the immunoconjugate is not dependent, and is not influenced by, the presence in the culture medium of the lysosomotropic agent chloroquine.