Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism

Parkinson's disease (PD) is a progressive neurodegenerative illness associated with a selective loss of dopaminergic neurons in the nigrostriatal pathway of the brain. Despite the overall rarity of the familial forms of PD, the identification of single genes linked to the disease has yielded crucial insights into possible mechanisms of neurodegeneration. Recently, a putative mitochondrial kinase, PINK1, has been found mutated in an inherited form of parkinsonism. Here, we describe that PINK1 mutations confer different autophosphorylation activity, which is regulated by the C-terminal portion of the protein. We also demonstrate the mitochondrial localization of both wild-type and mutant PINK1 proteins unequivocally and prove that a short N-terminal part of PINK1 is sufficient for its mitochondrial targeting.     

Inhibition by anti-HLA class II monoclonal antibodies of monocyte-dependent T cell proliferation induced by monoclonal antibody OKT3

The inhibitory effect of monoclonal antibodies (mAb) to monomorphic (locus-restricted and locus-shared) and polymorphic determinants of HLA class II antigens on the monocyte-dependent proliferation of T cells stimulated with mAb OKT3 has been studied. The effect appears to be specific, dose dependent, is not mediated by the Fc portion of mAb and reflects their interaction with the corresponding determinants. The anti-HLA class II mAb do not have to be present in the culture throughout the incubation period, but are essential in early phases of mAb OKT3 T cell activation. Both monocytes and T cells are the targets of the inhibition exerted by the anti-HLA class II mAb. Their inhibitory effect involves several steps in the sequence of events which leads to T cell proliferation, including interleukin (IL) 1 and 2 secretion, and IL2 receptor expression.     

Morphostructural characteristics of the vallate papillae in Bos taurus

The Morpho-structural characteristics of the vallate papillae of the bovine tongue were studied utilizing LM, SEM and TEM techniques. In the bovine, the vallate papillae are numerous and different in size. They have a prominent vallum papillae which surrounds a deep sulcus papillae. The sulcus has many elongated taste buds on its inner wall. Nervous fibers enter the taste bud and sometimes have rosary shaped axons. The gustative sensitivity of these animals may be instrumental, in their choice of food and avoidance of noxious plants.     

TUBB3 E410K syndrome: Case report and review of the clinical spectrum of TUBB3 mutations

The tubulinopathies refer to a wide range of brain malformations caused by mutations in one of the seven genes encoding different tubulin's isotypes. The β‐tubulin isotype III (TUBB3) gene has a primary function in nervous system development and axon generation and maintenance, due to its neuron‐specific expression pattern. A recurrent heterozygous mutation, c.1228G > A; p.E410K, in TUBB3 gene is responsible of a rare disorder clinically characterized by congenital fibrosis of the extraocular muscle type 3 (CFEOM3), intellectual disability and a wide range of neurological and endocrine abnormalities. Other mutations have been described spanning the entire gene and genotype–phenotype correlations have been proposed. We report on a 3‐year‐old boy in whom clinical exome sequencing allowed to identify a de novo TUBB3 E410K mutation as the molecular cause underlying a complex phenotype characterized by a severe bilateral palpebral ptosis refractory to eye surgery, psychomotor delay, absent speech, hypogonadism, celiac disease, and cyclic vomiting. Brain MRI revealed thinning of the corpus callosum with no evidence of malformation cortical dysplasia. We reviewed available records of patients with TUBB3 E410K mutation and compared their phenotype with the clinical outcome of patients with other mutations in TUBB3 gene. The present study confirms that TUBB3 E410K results in a clinically recognizable phenotype, unassociated to the distinct cortical dysplasia caused by other mutations in the same gene. Early molecular characterization of TUBB3 E410K syndrome is critical for targeted genetic counseling and prompt prospective care in term of neurological, ophthalmological, endocrine, and gastrointestinal follow‐up.     

Risk for SARS-CoV-2 Infection in Healthcare Workers,Turin, Italy

We measured severe acute respiratory syndrome coronavirus 2 spike protein subunits S1/S2 antibodies by using capillary electrophoresis and a chemiluminescence immunoassay for 5,444 active healthcare workers in Italy. Seroprevalence was 6.9% and higher among participants having contact with patients. Seroconversion was not observed in 37/213 previously infected participants.     

Primary Hepatic Lymphoma After Lung Transplantation: A Report of 2 Cases

BackgroundDiffuse large B-cell lymphoma (DLBCL) is the most common subtype of non–Hodgkin lymphoma in the posttransplant setting. Treatment is based on chemotherapy; surgery is still debated and should be performed in very select cases.MethodsWe observed 2 patients out of 300 who underwent lung transplantation in the Nouvel Hopital Civil between 2013 and 2019 with primary hepatic lymphoma. Chemotherapy with a rituximab-cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone protocol was performed in all patients. Mycophenolate mofetil was interrupted before treatment, and everolimus was introduced after chemotherapy by associating tacrolimus withdrawal.ResultsOne patient showed complete remission; after 7 years, no recurrence has been noticed. The second is still undergoing chemotherapy with no signs of disease progression.ConclusionsDLBCL risk is higher in solid organ transplant recipients than in the general population. Primary hepatic lymphoma diagnosis is often difficult and based on histologic findings after initial clinical and radiological suspicion of primary or secondary liver neoplasia. Diagnosis is challenging because no clinical, radiological, or biological features exist. Biopsy is always indicated for histologic confirmation. Chemotherapy is the mainstay of therapy, but surgery may be indicated in very select patients.     

Short-term multiorgan metabolic benefits of rapid weight loss after sleeve gastrectomy in severely obese patients

BackgroundSleeve gastrectomy (SG) has become the most prevalent bariatric-metabolic surgical approach in the United States. Its popularity among surgeons and patients is mainly due to a better safety profile and less overall morbidity, with broad benefits from a systemic and metabolic perspective.ObjectiveComprehensively describe the short-term multiorgan metabolic effects of rapid weight loss after SG.SettingAcademic hospital, United States.MethodsWe retrospectively reviewed the charts of patients that underwent SG at our institution between 2012 and 2016. We analyzed the required variables to calculate multiple risk scores, such as cardiovascular, hypertension, and diabetes risk scores. Furthermore, the renal and hepatic functions and the metabolic and hematologic profiles were assessed at 12 months of follow-up.ResultsA total of 1002 patients were included in the analysis. The percentage of excess body mass index loss was, on average, 65% at 12 months of follow-up. We observed a positive cardio-renal-hepatic improvement, demonstrated by a substantial reduction of the 10-year cardiovascular risk. We noticed an improvement of renal function, which was more significant in chronic kidney disease (stage ≥2), and a significant improvement on liver function tests (measured by decreased aspartate aminotransferase and alanine transaminase) at 12 months of follow-up. Our data also show a positive impact on decreasing the risk of developing hypertension and type 2 diabetes. There was a positive impact on the lipid profile, with the exception of low-density lipoprotein.ConclusionThere are significant short-term benefits on multiorgan metabolic parameters after rapid weight loss in severely obese patients undergoing sleeve gastrectomy.     

Esophageal adenocarcinoma after sleeve gastrectomy: actual or potential threat? Italian series and literature review

BackgroundSleeve gastrectomy (SG) leads to esophageal mucosal damage in an elevated percentage of cases, configuring a clinical condition of Barrett’s esophagus (BE) in a proportion as high as 15–18.8%. BE may rarely evolve into esophageal adenocarcinoma (EAC).ObjectivesTo raise awareness of BE as a precancerous lesion which may progress toward malignancy after this popular bariatric procedure.SettingBariatric referral centers, Italy.MethodsAll patients referred to our bariatric center who developed an EAC after SG between 2012 and 2019 were reviewed and consecutively included in this study. The available scientific literature regarding this complication is additionally reviewed.ResultsThe 3 male patients comprised in this case series underwent laparoscopic SG between 2012 and 2015 in different bariatric referral centers. Age and body mass index at baseline ranged from 21–54 years and 43.1–75.6 kg/m², respectively. All patients were lost to follow-up early after surgery (3.7 ± 1.4 months), and were diagnosed with EAC at a mean of 27.3 ± 7.6 months after SG. The 4 reported cases in the scientific literature developed an EAC at a mean of 32.5 ± 23 months from SG. Overall, a diagnosis of EAC was made approximately 30.3 ± 17.1 months postoperatively, which seems relatively and worryingly early after surgery.ConclusionAlthough the rate and probability of progression from BE to EAC is still not well defined, assuming that the rising popularity and execution of SG leads to a growth in the BE incidence, then the preoperative identification and stratification of cancer risk factors in this subset of patients is strongly encouraged. Clinical and endoscopic follow-ups are essential to allow for prevention and early diagnosis and for epidemiologic data collection purposes.     

Left ventricular mass index and ventricular contractility improvement in patients with severe obesity following rapid weight loss after bariatric surgery

BackgroundObesity is a well-known risk factor for heart disease, resulting in a broad spectrum of cardiovascular changes. Left ventricular mass (LVM) and contractility are recognized markers of cardiac function.ObjectivesTo determine the changes of LVM and contractility after bariatric surgery (BaS).SettingUniversity hospital, United StatesMethodsTo determine the cardiac changes in ventricular mass, ventricular contractility, and left ventricular shortening fraction (LVSF), we retrospectively reviewed the 2-dimensional echocardiographic parameters of patients with obesity who underwent BaS at our institution. We compared these results before and after BaS.ResultsA total of 40 patients met the inclusion criteria. The majority were females (57.5%; n = 23), with an average age of 63.5 ± 12.1. The excess body mass index (BMI) lost at 12 months was 48.9 ± 28.9%. The percent total weight loss after BaS was 16.46 ± 9.9%. The left ventricular mass was 234.9 ± 88.1 grams before and 181.5 ± 52.7 grams after BaS (P = .002). The LVM index was 101.3 ± 38.3 g/m² before versus 86.7 ± 26.6 g/m² after BaS (P = .005). The LVSF was 31% ± 8.8% before and 36.3% ± 8.2% after BaS (P = .007). We found a good correlation between the decrease in LVM index and the BMI after BaS (P = .03).ConclusionRapid weight loss results in a decrease of the LVM index, as well as improvement in the left ventricular muscle contractility. Our results suggest that there is left ventricular remodeling and an improvement of heart dynamics following bariatric surgery. Further studies are needed to better assess these findings.