Approximations in Credit Risk Models

In this thesis we present the intensity-based approach to consider default in a general local-stochastic volatility model with stochastic interest rate. In this setting we describe, as in [18], a technique to find approximate solutions of the corresponding partial differential equations and we provide numerical examples in the particular case of JDCEV and Vasicek model, respectively, for the dynamics of the asset and the short rate. Finally, we introduce a formula for the par CDS spreads and applying the approximation method we calibrate our intensity model to credit data finding the model parameters matching the default probabilities implicit in CDS prices (by bootstrapping) to the default probabilities implied by the model itself

Anti-inflammatory effects of fatty acid amide hydrolase inhibition in monocytes/macrophages from alzheimer’s disease patients

Growing evidence shows that the immune system is critically involved in Alzheimer’s disease (AD) pathogenesis and progression. The modulation and targeting of peripheral immune mechanisms are thus promising therapeutic or preventive strategies for AD. Given the critical involvement of the endocannabinoid (eCB) system in modulating immune functions, we investigated the potential role of the main elements of such a system, namely type-1 and type-2 cannabinoid receptors (CB1 and CB2), and fatty acid amide hydrolase (FAAH), in distinct immune cell populations of the peripheral blood of AD patients. We found that, compared to healthy controls, CB1 and CB2 expression was significantly lower in the B-lymphocytes of AD patients. Moreover, we found that CB2 was significantly lower and FAAH was significantly higher in monocytes of the same subjects. In contrast, T-lymphocytes and NK cells did not show any variation in any of these proteins. Of note, monocytic CB2 and FAAH levels significantly correlated with clinical scores. Furthermore, the pharmacological inactivation of FAAH in monocytes and monocyte-derived macrophages obtained from AD patients was able to modulate their immune responses, by reducing production of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-12, and enhancing that of the anti-inflammatory cytokine IL-10. Furthermore, FAAH blockade skewed AD monocyte-derived macrophages towards a more anti-inflammatory and pro-resolving phenotype. Collectively, our findings highlight a central role of FAAH in regulating AD monocytes/macrophages that could be of value in developing novel monocyte-centered therapeutic approaches aimed at promoting a neuroprotective environment

Use of Percutaneous Ethanol Injection Therapy for Recurrent Secondary Hyperparathyroidism after Subtotal Parathyroidectomy

We evaluated the efficacy of percutaneous ethanol injection therapy (PEIT) as a therapeutic option for recurrence of secondary hyperparathyroidism after subtotal parathyroidectomy in ESRD patients. Six patients underwent PEIT. A mean of 1.3 ± 0.8 ethanol injections was performed. Nodular volume was 1.5 ± 1.7 cm3, and 2.8 ± 2.8 cm3 of ethanol was injected per patient. After ethanol injection PTH decreased significantly (1897 ± 754 to 549 ± 863 pg/mL (P < .01)). There was also a reduction in serum calcium, phosphorus and calcium-phosphorus product. A positive and significant correlation was found between nodular volume with ethanol injected and time from parathyroidectomy. Only one patient required hospitalization due to severe hypocalcaemia. In other two cases, local discomfort and temporary mild dysphonia were registered. PEIT is an effective treatment to control recurrences of secondary hyperparathyroidism postsubtotal parathyroidectomy

High-dose steroid treatment increases free water transport in peritoneal dialysis patients

The water channel aquaporin-1 (AQP1) is the molecular counterpart of the ultrasmall pore that mediates free water transport during peritoneal dialysis (PD). Proof-of-principle studies performed in rats have shown that treatment with corticosteroids upregulates the expression of AQP1 in the peritoneal capillaries, causing a significant increase in free water transport. Whether such a beneficial effect could be observed in end-stage renal disease patients treated by PD remains unknown. Peritoneal transport parameters were evaluated in three patients on PD, shortly before and after living-donor renal transplantation and treatment with high-dose methylprednisolone (1.0-1.2 g/m2). As compared with pre-transplantation values, the post-transplantation test revealed an ∼2-fold increase in the sodium sieving and ultrasmall pore ultrafiltration volume, suggesting an effect on AQP1 water channels. In contrast, there was no change in the parameters of small solute transport. The direct involvement of AQP1 in these changes is suggested by the expression of glucocorticoid receptors in the human peritoneum and the presence of conserved glucocorticoid response elements in the promoter of the human AQP1 gen

Impairment of DHA synthesis alters the expression of neuronal plasticity markers and the brain inflammatory status in mice

Docosahexaenoic acid (DHA) is a ω-3 fatty acid typically obtained from the diet or endogenously synthesized through the action of elongases (ELOVLs) and desaturases. DHA is a key central nervous system constituent and the precursor of several molecules that regulate the resolution of inflammation. In the present study, we questioned whether the impaired synthesis of DHA affected neural plasticity and inflammatory status in the adult brain. To address this question, we investigated neural and inflammatory markers from mice deficient for ELOVL2 (Elovl2−/−), the key enzyme in DHA synthesis. From our findings, Elovl2−/− mice showed an altered expression of markers involved in synaptic plasticity, learning, and memory formation such as Egr-1, Arc1, and BDNF specifically in the cerebral cortex, impacting behavioral functions only marginally. In parallel, we also found that DHA-deficient mice were characterized by an increased expression of pro-inflammatory molecules, namely TNF, IL-1β, iNOS, caspase-1 as well as the activation and morphologic changes of microglia in the absence of any brain injury or disease. Reintroducing DHA in the diet of Elovl2−/− mice reversed such alterations in brain plasticity and inflammation. Hence, impairment of systemic DHA synthesis can modify the brain inflammatory and neural plasticity status, supporting the view that DHA is an essential fatty acid with an important role in keeping inflammation within its physiologic boundary and in shaping neuronal functions in the central nervous system

Secondary cytomegalovirus infections: How much do we still not know? Comparison of children with symptomatic congenital cytomegalovirus born to mothers with primary and secondary infection

congenital cytomegalovirus (cCMV) infection can follow primary and secondary maternal infection. growing evidence indicate that secondary maternal infections contribute to a much greater proportion of symptomatic cCMV than was previously thought. We performed a monocentric retrospective study of babies with cCMV evaluated from august 2004 to february 2021; we compared data of symptomatic children born to mothers with primary or secondary infection, both at birth and during follow up. among the 145 babies with available data about maternal infection, 53 were classified as having symptomatic cCMV and were included in the study: 40 babies were born to mothers with primary infection and 13 babies were born to mothers with secondary infection. Analyzing data at birth, we found no statistical differences in the rate of clinical findings in the two groups, except for unilateral sensorineural hearing loss (SNHL) which was significantly more frequent in patients born to mother with secondary infection than in those born to mother with primary infection (46.2 vs. 17.5%, P = 0.037). during follow up, we found a higher rate of many sequelae (tetraparesis, epilepsy, motor and speech delay, and unilateral SNHL) in the group of children born to mothers with secondary infection, with a statistical difference for tetraparesis and unilateral SNHL. otherwise, only children born to mothers with primary infection presented bilateral SNHL both at birth and follow up. Our data suggest that the risk of symptomatic cCMV and long-term sequelae is similar in children born to mother with primary and secondary CMV infection; it is important to pay appropriate attention to seropositive mothers in order to prevent reinfection and to detect and possibly treat infected babies

Renal Transplantation in a patient with Recessive Dystrophic Epidermolysis Bullosa: a case report

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genodermatosis characterized by abnormalities in the anchoring fibrils which attach the basal cell layer of the epidermis to the underlying structures. A characteristic feature of this disorder is the presence of recurrent blistering or erosions, the result of even minor traction to these tissues. Patients with RDEB frequently develop chronic renal failure, and require renal replacement therapy being a major cause of morbidity and mortality. The role of renal transplantation in these patients is scarcely known.We present the case of an end-stage renal disease patient with RDEB treated by renal transplantation and his follow-up during a period of 83 months after the transplant. In this period, there were very low frequency of serious infections as well as the absence of skin tumors.Renal transplantation could be an alternative to renal replacement therapy in epidermolysis bullosa patients with end-stage renal disease, reducing the comorbidities associated with this treatment.</p

Ejection of damaged mitochondria and their removal by macrophages ensure efficient thermogenesis in brown adipose tissue

Recent findings have demonstrated that mitochondria can be transferred between cells to control metabolic homeostasis. Although the mitochondria of brown adipocytes comprise a large component of the cell volume and undergo reorganization to sustain thermogenesis, it remains unclear whether an intercellular mitochondrial transfer occurs in brown adipose tissue (BAT) and regulates adaptive thermogenesis. Herein, we demonstrated that thermogenically stressed brown adipocytes release extracellular vesicles (EVs) that contain oxidatively damaged mitochondrial parts to avoid failure of the thermogenic program. When re-uptaken by parental brown adipocytes, mitochondria-derived EVs reduced peroxisome proliferator-activated receptor-γ signaling and the levels of mitochondrial proteins, including UCP1. Their removal via the phagocytic activity of BAT-resident macrophages is instrumental in preserving BAT physiology. Depletion of macrophages in vivo causes the abnormal accumulation of extracellular mitochondrial vesicles in BAT, impairing the thermogenic response to cold exposure. These findings reveal a homeostatic role of tissue-resident macrophages in the mitochondrial quality control of BAT

Neonatal invasive candidiasis in low-and-middle-income countries: data from the NeoOBS study

Neonatal invasive candidiasis (NIC) has significant morbidity and mortality. Reports have shown a different profile of those neonates affected with NIC and of fluconazole resistant Candida spp. isolates in low-and-middle-income -countries (LMICs) compared to high-income-countries (HIC). We describe the epidemiology, Candida spp. distribution, treatment and outcomes of neonates with NIC from LMICs enrolled in a global, prospective, longitudinal, observational cohort study (NeoOBS) of hospitalised infants < 60 days postnatal age with sepsis (August 2018-February 2021). 127 neonates from 14 hospitals in 8 countries with Candida spp. isolated from blood culture were included. Median gestational age of affected neonates was 30 weeks (IQR: 28-34) and median birth weight was 1270 g (IQR: 990-1692). Only a minority had high risk criteria, such as being born < 28 weeks, 19% (24/127), or birth weight < 1000 g, 27% (34/127). The most common Candida species were C. albicans (n = 45, 35%), C. parapsilosis (n = 38, 30%) and Candida auris (n = 18, 14%). The majority of C. albicans isolates were fluconazole susceptible, whereas 59% of C. parapsilosis isolates were fluconazole resistant. Amphotericin B was the most common antifungal used [74% (78/105)], followed by fluconazole [22% (23/105)]. Death by day 28 post-enrolment was 22% (28/127). To our knowledge, this is the largest multi-country cohort of NIC in LMICs. Most of the neonates would not have been considered at high risk for NIC in HICs. A substantial proportion of isolates was resistant to first choice fluconazole. Understanding the burden of NIC in LMIC is essential to guide future research and treatment guidelines