Exposure to obinutuzumab does not affect outcomes of SARS-CoV-2 infection in vaccinated patients with newly diagnosed advanced-stage follicular lymphoma.

URBAN is a multicentric, ambispective study evaluating the effectiveness and safety of obinutuzumab-based immuno-chemotherapy and maintenance in patients with untreated advanced follicular lymphoma (FL). The study began before the COVID-19 emergency declaration in Italy. It is currently ongoing for follow-up, and the enrolment timeline encompassed different stages of the pandemic, various vaccination roll-out phases and prevalence of SARS-CoV-2 variants. Outcomes of interest of the present sub-analysis included SARS-CoV-2 infection rates and COVID-19-related hospitalizations/deaths. At data cut-off, 86 (28.8%) and 213 patients (71.2%) were treated before and during/after the COVID-19 outbreak respectively; 294 (98.3%) completed the induction, 31 (10.4%) completed maintenance and 170 (56.9%) were still on maintenance. Overall, 245 patients (81.9%) received at least one SARS-CoV-2 vaccine dose: 13.5%, 31.4% and 55.1% received one, two and three doses respectively. We observed a substantial decrease in COVID-19-related mortality rates in pre- versus post-vaccination phases, along with a reduction in COVID-19-related outcomes due to the shift from alpha/delta to omicron variant predominance. No differences emerged between patients given maintenance or not, although the schedule was modified in 65% of cases. To our knowledge, URBAN represents the largest dataset of COVID-19-related outcomes in FL patients extensively exposed to obinutuzumab. ClinicalTrials.gov identifier: NCT04034056.

Perioperative pain management after scapular tip free flap harvesting for head and neck reconstruction using mini-catheters to inject the local anesthetic.

PURPOSE: Although functional and esthetic results after the use of a scapular tip free flap (STFF) in head and neck reconstruction, and the related donor-site morbidity, have been extensively described, data regarding acute postoperative donor-site pain management are lacking. Purpose of this study is to explore the use of mini-catheters to administer local anesthetics for donor-site pain management after reconstruction using STFF. METHODS: Patients who underwent head and neck reconstruction using a STFF were prospectively enrolled and, through a perineural catheter placed in the donor site during the surgical procedure, a bolus of chirochaine was injected before the patient regained consciousness and at 8, 16, and 24 h postoperatively. Before and 40 min after each dose administration, donor-site pain on a numerical rating scale (NRS; 0-10) was evaluated. RESULTS: Study population consisted of 20 patients (40-88 years). At 8 h, the pain scores before and after the injection were 0-10 (mean 3.35) and 0-5 (mean 1.25), respectively. At 16 h, the pain scores before and after the injection were 0-8 (mean 2.55) and 0-4 (mean 0.55), respectively. At 24 h, the pain scores before and after the injection were 0-8 (mean 1.30) and 0-4 (mean 0.30), respectively. CONCLUSION: Statistical analysis confirmed a significant difference between the pain scores before and after administration at 8, 16, and 24 h (p < 0.001, p < 0.001, and p = 0.003, respectively). Mini-catheters for local anesthetic administration represent an effective strategy for pain control after STFF harvesting for head and neck reconstruction.

Idiopathic erythrocytosis: a germline disease?

Polycythemia Vera (PV) is typically caused by V617F or exon 12 JAK2 mutations. Little is known about Polycythemia cases where no JAK2 variants can be detected, and no other causes identified. This condition is defined as idiopathic erythrocytosis (IE). We evaluated clinical-laboratory parameters of a cohort of 56 IE patients and we determined their molecular profile at diagnosis with paired blood/buccal-DNA exome-sequencing coupled with a high-depth targeted OncoPanel to identify a possible underling germline or somatic cause. We demonstrated that most of our cohort (40/56: 71.4%) showed no evidence of clonal hematopoiesis, suggesting that IE is, in large part, a germline disorder. We identified 20 low mutation burden somatic variants (Variant allelic fraction, VAF, < 10%) in only 14 (25%) patients, principally involving DNMT3A and TET2. Only 2 patients presented high mutation burden somatic variants, involving DNMT3A, TET2, ASXL1 and WT1. We identified recurrent germline variants in 42 (75%) patients occurring mainly in JAK/STAT, Hypoxia and Iron metabolism pathways, among them: JAK3-V722I and HIF1A-P582S; a high fraction of patients (48.2%) resulted also mutated in homeostatic iron regulatory gene HFE-H63D or C282Y. By generating cellular models, we showed that JAK3-V722I causes activation of the JAK-STAT5 axis and upregulation of EPAS1/HIF2A, while HIF1A-P582S causes suppression of hepcidin mRNA synthesis, suggesting a major role for these variants in the onset of IE.

Air change rates and infection risk in school environments: Monitoring naturally ventilated classrooms in a northern Italian urban context.

The importance of building ventilation in avoiding long-distance airborne transmission has been highlighted with the advent of the COVID-19 pandemics. Among others, school environments, in particular classrooms, present criticalities in the implementation of ventilation strategies and their impact on indoor air quality and risk of contagion. In this work, three naturally ventilated school buildings located in northern Italy have undergone monitoring at the end of the heating season. Environmental parameters, such as CO2 concentration and indoor/outdoor air temperature, have been recorded together with the window opening configurations to develop a two-fold analysis: i) the estimation of real air change rates through the transient mass balance equation method, and ii) the individual infection risk via the Wells-Riley equation. A strong statistical correlation has been found between the air change rates and the windows opening configuration by means of a window-to-volume ratio between the total opening area and the volume of the classroom, which has been used to estimate the individual infection risk. Results show that the European Standard recommendation for air renewal could be achieved by a window opening area of at least 1.5 m2, in the most prevailing Italian classrooms. Furthermore, scenarios in which the infector agent is a teacher show higher individual infection risk than those in which the infector is a student. In addition, the outcomes serve school staff as a reference to ensure adequate ventilation in classrooms and keep the risk of infection under control based on the number of the students and the volume of the classroom.

Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX.

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX. INTRODUCTION: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD). METHODS: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted ß-coefficients. RESULTS: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination. CONCLUSION: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.

Thoughts and concerns of patients at hospital discharge after lumbar spine surgery. A qualitative study.

PURPOSE: The increased rate of surgical interventions point to the necessity to investigate the patient's experience from a biopsychosocial perspective. The aim of this study was to investigate the thoughts and concerns of patients undergoing spinal surgery for lumbar degenerative disease at the time of their discharge from hospital. METHODS: Semi-structured interviews were conducted with 28 patients. The questions investigated possible concerns associated to discharging them home. A content analysis was performed by a multidisciplinary group to identify the main themes that emerged from the interviews. RESULTS: The patients were satisfied with the surgeons' preoperative explanations and description of expected prognosis. However, they were disappointed with the lack of information at hospital discharge, in particular regarding practical and behavioral recommendations. The patients expressed clear concerns about being left alone to deal with possible complications or difficulties they may encounter when returning home. CONCLUSION: This study underlined the patients' need for a comprehensive psychological guidance and possibly a person of reference during the post-operative process. Discussing discharge with the patient was emphasized as an important issue to improve patients' compliance to the recovery process itself. Putting these elements into practice should help spine surgeons to manage better hospital discharge.IMPLICATIONS FOR REHABILITATIONA comprehensive discussion with the patient at the time of hospital discharge is clearly stressed as an important issue to improve patients' adherence to the recovery process.The patients complained of a lack of information when returning home, in particular regarding practical and behavioral recommendations.The patients expressed clear concerns about possible complications or difficulties they may encounter when returning home and they expressed their need to know whom they can contact for help if needed.A better understanding of the thoughts and concerns of patients undergoing spinal surgery at the time of their discharge from hospital should help spine surgeons to improve the management of hospital discharge and the post-operative recovery.

Serum neurofilament levels correlate with electrodiagnostic evidence of axonal loss in paclitaxel-induced peripheral neurotoxicity.

INTRODUCTION: Paclitaxel-induced peripheral neurotoxicity (PIPN) typically manifests as a predominantly sensory axonopathy. Nerve conduction studies (NCS) represent the gold standard method to quantify axonal impairment in PIPN. Serum neurofilament light chain (sNfL) levels are emerging biomarkers for quantifying axonal damage in peripheral neuropathies. To date, the association between NCS abnormalities and sNfL levels during paclitaxel-based chemotherapy has not been specifically addressed. METHODS: We prospectively conducted longitudinal measurement of sNfL levels in 27 chemotherapy-naïve breast cancer patients and correlated conventional NCS recordings with sNfL in 22 of them, before (T0) and after (T1) 12 cycles of weekly paclitaxel-based therapy. RESULTS: PIPN was diagnosed in 24/27 patients (88%) after completion of the 12-week paclitaxel-based chemotherapy regimen. Serum NfL levels (pg/mL) were significantly higher at T1 compared to T0 (T0: 18.50 ± 12.88 vs T1: 255.80 ± 194.16; p < 0.001). The increase of sNfL levels at T1 significantly correlated with the decrease or abolishment of amplitudes recorded from the sural nerve (r = 0.620; p = 0.0035), sensory radial (r = 0.613; p = 0.005), sensory ulnar (r = 0.630; p = 0.005), and peroneal motor (r = 0.568; p = 0.024) nerves. CONCLUSION: sNfL levels proportionally increase during chemotherapy administration and significantly correlate with NCS axonal abnormalities in patients with PIPN. A multimodal testing approach employing both sNfL and NCS might improve the PIPN diagnostic accuracy.

Incidence and risk factors of bacterial sepsis and invasive fungal infection in neonates and infants requiring major surgery: an Italian multicentre prospective study.

BACKGROUND: Limited data are currently available on the incidence rates and risk factors for bacterial sepsis and invasive fungal infections (IFIs) among neonates and infants undergoing major surgery. AIM: To assess the incidence of bacterial sepsis and IFI, fungal colonization, risk factors for sepsis, and mortality in neonates and infants aged <3 months undergoing major surgery. METHODS: A multicentre prospective study was conducted involving 13 level-3 neonatal intensive care units in Italy, enrolling all infants aged ≤3 months undergoing major surgery. FINDINGS: From 2018 to 2021, 541 patients were enrolled. During hospitalization, 248 patients had a bacterial infection, and 23 patients had a fungal infection. Eighty-four patients were colonized by fungal strains. Overall, in-hospital mortality was 2.8%, but this was higher in infected than in uninfected infants (P = 0.034). In multivariate analysis, antibiotic exposure before surgery, ultrasound-guided or surgical placement of vascular catheters, vascular catheterization duration, and gestational age ≤28 weeks were all associated with bacterial sepsis. The risk of IFI was markedly higher in colonized infants (odds ratio (OR): 8.20; P < 0.001) and was linearly associated with the duration of vascular catheterization. Fungal colonization in infants with abdominal surgery increased the probability of IFI 11-fold (OR: 11.1; P < 0.001). CONCLUSION: Preventive strategies such as early removal of vascular catheters and the fluconazole prophylaxis should be considered to prevent bacterial and fungal sepsis in infants undergoing abdominal surgery, and even more so in those with fungal colonization.

Transplantation to save the life, TSH screening to save the brain: A report and brief literature review of autoimmune thyroid disease after HSCT for severe combined immunodeficiency.

Autoimmune thyroid disease has been described as a complication of HSCT for different indications and as a manifestation of inborn errors of immunity, like SCID. A 1-month female was diagnosed with RAG1-mutated SCID and received allogenic HSCT. She developed autoimmune hypothyroidism 5 months after transplantation and was treated with levo-thyroxine with a good response. Autoimmune thyroid disease can develop after HSCT during the immune reconstitution phase, leading to potentially severe neurological and growth impairment, particularly in SCID patients, often transplanted during the first year of life. Recommendations regarding early and frequent vigilance for thyroid function are needed in these patients.

Ventilation strategies to reduce airborne transmission of viruses in classrooms: A systematic review of scientific literature.

The recent pandemic due to SARS-CoV-2 has brought to light the need for strategies to mitigate contagion between human beings. Apart from hygiene measures and social distancing, air ventilation highly prevents airborne transmission within enclosed spaces. Among others, educational environments become critical in strategic planning to control the spread of pathogens and viruses amongst the population, mainly in cold conditions. In the event of a virus outbreak - such as COVID or influenza - many school classrooms still lack the means to guarantee secure and healthy environments. The present review examines school contexts that implement air ventilation strategies to reduce the risk of contagion between students. The analysed articles present past experiences that use either natural or mechanical systems assessed through mathematical models, numerical models, or full-scale experiments. For naturally ventilated classrooms, the studies highlight the importance of the architectural design of educational spaces and propose strategies for aeration control such as CO2-based control and risk-infection control. When it comes to implementing mechanical ventilation in classrooms, different systems with different airflow patterns are assessed based on their ability to remove airborne pathogens considering parameters like the age of air and the generation of airflow streamlines. Moreover, studies report that programmed mechanical ventilation systems can reduce risk-infection during pandemic events. In addition to providing a systematic picture of scientific studies in the field, the findings of this review can be a valuable reference for school administrators and policymakers to implement the best strategies in their classroom settings towards reducing infection risks.

'Guess who'? An Italian multicentric study on pigmentation traits prevalence in endometriosis localizations.

OBJECTIVES: Previous evidence seems to support the more common presence of certain pigmentation types in women with endometriosis. The aim of this study was to assess the association of certain somatic phenotypes with specific localizations of the disease. The genetic makeup of those somatic traits may will help in better define the disease pathogenesis. STUDY DESIGN: Multicentric, retrospective study of women aged 18 to 45 with histologically confirmed endometriosis. 575 patients were recruited at eleven different Italian endometriosis clinics from March 2015 to January 2021. Data regarding clinical and surgical features were recorded following the self-administered endometriosis patient questionnaire and the surgical standard of reports approved by the World Endometriosis Research Foundation (WERF). Pigmentation types/somatic phenotypes frequencies among endometriosis localizations were reported. A logistic regression analysis was performed to determine somatic types independently associated with disease' localizations. RESULTS: Having green eyes increased by ∼4 folds (OR 3.7; 95% CI: 1.42-9.61; p = 0.007) the risk of having a ureteral nodule, whereas brown/black eyes decreased this risk (OR 0.34; 95% CI: 0.13-0.87; p = 0.025). Consistently, the combination of green eyes and blonde/light brown hairs increased the odds of ureteral endometriosis by more than 5 folds (OR 5.40; 95%CI: 2.02-14.49; p = 0.001), even after correction for anthropometric confounders (aOR 5.85; 95% CI: 2.13-16.09; p < 0.001). CONCLUSIONS: The association between endometriosis and pigmentary traits has been herein confirmed, with the novel finding of the possible predisposition of ureteral endometriosis in patients with green eyes and blonde/light brown hairs. Further investigation on the genetic makeup of somatic traits may provide new inroads also into the molecular aspects of endometriosis leading to a better understanding of this complex disease.

Update of the fracture risk prediction tool FRAX: a systematic review of potential cohorts and analysis plan.

We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. INTRODUCTION: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. METHODS: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. RESULTS: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. CONCLUSIONS: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

Are seizures associated with neuroschistosomiasis mansoni? An exploratory survey in an endemic area of Brazil.

BACKGROUND: Deposition of Schistosoma mansoni eggs in the brain of patients with hepatosplenic schistosomiasis (HS-SM) is frequent and usually asymptomatic. However, it is questioned whether it could cause seizures. Thus, we investigated the occurrence of seizures in these patients and also searched for parameters associated with this disorder. METHODS: In a cross-sectional survey, we compared 128 patients with HS-SM with 102 patients with portal hypertension due to compensated chronic hepatic disease of other etiologies. A standardized questionnaire, emphasizing epilepsy-related parameters, was applied to all participants. RESULTS: Eight (6.3%) patients with HS-SM had a history of seizures, whereas this condition was reported by three (2.9%) individuals from the comparison group (p=0.354). None of the variables were associated with the occurrence of seizures, either in univariate or in multivariate analysis. CONCLUSIONS: The frequency of seizures was similar in both study groups. However, it was higher than that described in population-based studies. Thus, we hypothesize that HS-SM individuals may have a higher frequency of seizure. The lack of difference between the two study groups may be explained by the inclusion of cases of HS-MS overlapping other chronic liver diseases in the comparison group, because this finding is relatively common in schistosome-endemic areas.

Reference microarchitectural values measured by HR-pQCT in a Franco-Swiss cohort of young adult women.

Bone microarchitecture assessed by high-resolution peripheral quantitative computed tomography varies across populations of different origin. The study presents a reference dataset of microarchitectural parameters in a homogeneous group of participants aged within 22-27 range determined by a discriminant analysis of a larger cross-sectional cohort of 339 women. INTRODUCTION: High-resolution peripheral quantitative computed tomography (HR-pQCT) non-invasively measures three-dimensional bone microarchitectural parameters and volumetric bone mineral density. Previous studies established normative reference HR-pQCT datasets for several populations, but there were few data assessed in a reference group of young women with Caucasian ethnicity living in Western Europe. It is important to obtain different specific reference dataset for a valid interpretation of cortical and trabecular microarchitecture data. The aim of our study was to find the population with the most optimal bone status in order to establish a descriptive reference HR-pQCT dataset in a young and healthy normal-weight female cohort living in a European area including Geneva, Switzerland, Lyon and Saint-Etienne, France. METHODS: We constituted a cross-sectional cohort of 339 women aged 19-41 years with a BMI > 18 and < 30 kg/m2. All participants had HR-pQCT measurements at both non-dominant distal radius and tibia sites. RESULTS: We observed that microarchitectural parameters begin to decline before the age of 30 years. Based on a discriminant analysis, the optimal bone profile in this population was observed between the age range of 22 to 27 years. Consequently, we considered 43 participants aged 22-27 years to establish a reference dataset with median values and percentiles. CONCLUSION: This is the first study providing reference values of HR-pQCT measurements considering specific age bounds in a Franco-Swiss female cohort at the distal radius and tibia sites.

Pathophysiology of aniridia-associated keratopathy: Developmental aspects and unanswered questions.

Aniridia, a rare congenital disease, is often characterized by a progressive, pronounced limbal insufficiency and ocular surface pathology termed aniridia-associated keratopathy (AAK). Due to the characteristics of AAK and its bilateral nature, clinical management is challenging and complicated by the multiple coexisting ocular and systemic morbidities in aniridia. Although it is primarily assumed that AAK originates from a congenital limbal stem cell deficiency, in recent years AAK and its pathogenesis has been questioned in the light of new evidence and a refined understanding of ocular development and the biology of limbal stem cells (LSCs) and their niche. Here, by consolidating and comparing the latest clinical and preclinical evidence, we discuss key unanswered questions regarding ocular developmental aspects crucial to AAK. We also highlight hypotheses on the potential role of LSCs and the ocular surface microenvironment in AAK. The insights thus gained lead to a greater appreciation for the role of developmental and cellular processes in the emergence of AAK. They also highlight areas for future research to enable a deeper understanding of aniridia, and thereby the potential to develop new treatments for this rare but blinding ocular surface disease.

Diagnosis and management of osteoporosis in chronic kidney disease stages 4 to 5D: a call for a shift from nihilism to pragmatism.

The European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) CKD-MBD working group, in collaboration with the Committee of Scientific Advisors of the International Osteoporosis Foundation, published a position paper for the diagnosis and management of osteoporosis in patients with CKD stages 4-5D (eGFR < 30 ml/min 1.73 m2). The present article reports and summarizes the main recommendations included in this 2021 document. The following areas are reviewed: diagnosis of osteoporosis; risk factors for fragility fractures; fracture risk assessment; intervention thresholds for pharmacological intervention; general and pharmacological management of osteoporosis; monitoring of treatment, and systems of care, all in patients with CKD stages 4-5D. Guidance is provided for clinicians caring for CKD stages 4-5D patients with osteoporosis, allowing for a pragmatic individualized diagnostic and therapeutic approach as an alternative to current variations in care and treatment nihilism.

The best temperature range to acquire reliable thermal infrared spectra from orbit.

Solar System bodies undergo to daily and periodical variations of temperature that mainly depend on their closeness to the Sun. It is known that mineral expansion and contraction due to such variations modify the thermal infrared spectra acquired on solid surfaces. Therefore, it becomes crucial to know the best temperature range at which the acquisition itself should be carried out to get reliable information on the mineralogy of such bodies. Here we provide the thermal expansion of olivine between 20 and 298 K determined by X-ray diffraction. Our data reveal the non-linear behaviour of silicates that undergo to low temperatures, where volume variations appear positively correlated with temperatures. Subtle bond-length variations occurring at low temperatures are then expected to minimally affect vibrational absorption positions. We suggest that thermal infrared spectra of those Solar-System surfaces that are not exceeding 300 K provide reliable information about not only the silicate mineral identification but also on their chemical composition, regardless of the instantaneous temperature.

Cannabidiol in the prelimbic cortex modulates the comorbid condition between the chronic neuropathic pain and depression-like behaviour in rats: The role of medial prefrontal cortex 5-HT1A and CB1 receptors.

The prelimbic division (PrL) of the medial prefrontal cortex (mPFC) is a cerebral division that is putatively implicated in the chronic pain and depression. We investigated the activity of PrL cortex neurons in Wistar rats that underwent chronic constriction injury (CCI) of sciatic nerve and were further subjected to the forced swimming (FS) test and mechanical allodynia (by von Frey test). The effect of blockade of synapses with cobalt chloride (CoCl2), and the treatment of the PrL cortex with cannabidiol (CBD), the CB1 receptor antagonist AM251 and the 5-HT1A receptor antagonist WAY-100635 were also investigated. Our results showed that CoCl2 decreased the time spent immobile during the FS test but did not alter mechanical allodynia. CBD (at 15, 30 and 60 nmol) in the PrL cortex also decreased the frequency and duration of immobility; however, only the dose of 30 nmol of CBD attenuated mechanical allodynia in rats with chronic NP. AM251 and WAY-100635 in the PrL cortex attenuated the antidepressive and analgesic effect caused by CBD but did not alter the immobility and the mechanical allodynia when administered alone. These data show that the PrL cortex is part of the neural substrate underlying the comorbidity between NP and depression. Also, the previous blockade of CB1 cannabinoid receptors and 5-HT1A serotonergic receptors in the PrL cortex attenuated the antidepressive and analgesics effect of the CBD. They also suggest that CBD could be a potential medicine for the treatment of depressive and pain symptoms in patients with chronic NP/depression comorbidity.

Higher serum levels of a cathepsin K-generated periostin fragment are associated with fractures in postmenopausal women with primary hyperparathyroidism: a pilot study.

The only difference between fractured and non-fractured postmenopausal women with PHPT of same sex, age, and BMI was a significantly mean higher serum k-periostin level. K-periostin value was associated with fracture at any site (odds ratio 1.044, 95% CI 1.005-1.091, p = 0.03). INTRODUCTION: To assess serum k-periostin fragment levels in patients with primary hyperparathyroidism (PHPT), fractured and non-fractured matched for sex, age, and body mass index. METHODS: Twenty-five Caucasian fractured postmenopausal women with PHPT (group Fx) and 25 PHPT non-fractured (group NFx) were enrolled. Each patient underwent DXA scan at lumbar, hip, and forearm, spine X-ray, and biochemical evaluation of calcium metabolism. For k-periostin analyses, we utilized a specific ELISA test that detects CatK-generated fragment levels in the bloodstream. RESULTS: We found no difference in mean BMD and bone turnover marker values between Fx and NFx groups. Prevalence of osteoporosis was not significantly different in Fx vs NFx (72% vs 60%, p = 0.55). Among Fx, 16% reported multiple fractures, 28% morphometric vertebral fractures, 4% femoral fractures, 28% non-vertebral non-femoral fractures, and 8% wrist fractures. The only detectable difference between Fx and NFx group was a significantly mean higher k-periostin serum level (46.2 ± 21.4 vs 34.7 ± 13.5 ng/ml, p = 0.02). K-periostin was associated with fracture at any site (odds ratio 1.044, 95% CI 1.005-1.091, p = 0.03). No difference in mean k-periostin values was found between patients with vertebral fracture vs those with non-vertebral fracture, and between those with multiple fractures vs those with single fracture. CONCLUSION: Serum k-periostin is significantly associated with fracture in PHPT. If confirmed by further studies, k-periostin could be considered a new marker of bone fragility in PHPT, independently of BMD.