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Introduction: Lateral fractures of proximal femur are the most frequent fractures in elderly people. Internal fixation using medullary nails is the gold standard of treatment (Gamma 3 nail is the most implanted device) due to reduced incidence of complications than other devices. We report our experience in treating this kind of fractures with Gamma 3 nail, between January 2015 and December 2021. Methods: We performed a retrospective cohort study of patients treated in our orthopaedic department; level of clinical care is III: 559 patients (431 females and 128 males, with an average age of 85.3 years) with lateral femoral neck fracture. All patients were surgically treated with Gamma 3 standard nail (SGN). We evaluated preliminary X-rays to classify fractures, according to AO-OTA classification and post-operative X-ray to verify cephalic screw position site, according to areas described by Cleveland in 1959: we measured tip-to-apex distance (TAD) and tip-to-apex calcar referred distance (CalTAD). Finally Chang reduction quality criteria (CRQC) for fracture reduction of trochanteric fractures were determined using preoperative or postoperative Antero-Posterior (AP) and lateral radiographs in a Picture Archiving and Communication System (PACS). Incidence of cut-out was evaluated in relation with these parameters. Patients were divided into 2 groups: first group had cephalic screw in optimal positions (5-8-9), the other group had cephalic screw in other positions. Results: In 328 patients (58.7%) screw was in positions 5-8-9, in 231 patients (41.2%) screw was in not-optimal position. Median TAD was 19.1 ± 7.0 mm (range = 0.0–50.5); in 463 patients (82.8%) TAD was ≤ 25 mm. Median CalTAD was 21.4 ± 4.7 mm (range = 5.7–39.2); in 105 patients (79.4%) CalTAD was ≤ 25 mm. Cut-out was observed in 8 cases (1.43%). Multivariate analysis showed a significant correlation (p 25 mm. Cephalic screw position did not influence incidence of cut-out. Discussion: In order to obtain fracture healing with a low risk of failure, in particular cut-out, it is necessary to obtain good reduction of fracture and optimal lag screw position in order to achieve a TAD inferior to 25 mm.

Intrinsically disordered proteins (IDPs) perform a broad range of functions in biology, suggesting that the ability to design IDPs could help expand the repertoire of proteins with novel functions. Computational design of IDPs with specific conformational properties has, however, been difficult because of their substantial dynamics and structural complexity. We describe a general algorithm for designing IDPs with specific structural properties. We demonstrate the power of the algorithm by generating variants of naturally occurring IDPs that differ in compaction, long-range contacts, and propensity to phase separate. We experimentally tested and validated our designs and analyzed the sequence features that determine conformations. We show how our results are captured by a machine learning model, enabling us to speed up the algorithm. Our work expands the toolbox for computational protein design and will facilitate the design of proteins whose functions exploit the many properties afforded by protein disorder. [ABSTRACT FROM AUTHOR]

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of renal failure. The pathogenesis of the disease encompasses several pathways and metabolic alterations, including the hyperactivation of mTOR and suppression of AMPK signaling pathways, as well as mitochondrial dysfunction. This metabolic reprogramming makes epithelial cyst-lining cells highly dependent on glucose for energy and unable to oxidize fatty acids. Evidence suggests that high-carbohydrate diets may worsen the progression of ADPKD, providing the rationale for treating ADPKD patients with calorie restriction and, in particular, with ketogenic dietary interventions, already used for other purposes such as in overweight/obese patients or in the treatment of refractory epilepsy in children. Preclinical studies have demonstrated that calorie restriction may prevent and/or slow disease progression by inducing ketosis, particularly through increased beta-hydroxybutyrate (BHB) levels, which may modulate the metabolic signaling pathways altered in ADKPK. In these patients, although limited, ketogenic intervention studies have shown promising beneficial effects. However, larger and longer randomized controlled trials are needed to confirm their tolerability and safety in long-term maintenance and their additive role in the therapy of polycystic kidney disease. [ABSTRACT FROM AUTHOR]

We propose a nonparametric compound Poisson model for underreported count data that introduces a latent clustering structure for the reporting probabilities. The latter are estimated with the model's parameters based on experts' opinion and exploiting a proxy for the reporting process. The proposed model is used to estimate the prevalence of chronic kidney disease in Apulia, Italy, based on a unique statistical database covering information on m = 258 municipalities obtained by integrating multisource register information. Accurate prevalence estimates are needed for monitoring, surveillance, and management purposes; yet, counts are deemed to be considerably underreported, especially in some areas of Apulia, one of the most deprived and heterogeneous regions in Italy. Our results agree with previous findings and highlight interesting geographical patterns of the disease. We compare our model to existing approaches in the literature using simulated as well as real data on early neonatal mortality risk in Brazil, described in previous research: the proposed approach proves to be accurate and particularly suitable when partial information about data quality is available. [ABSTRACT FROM AUTHOR]

C3 glomerulopathy is a rare disease, characterized by an abnormal activation of the complement's alternative pathway that leads to the accumulation of the C3 component in the kidney. The disease recurs in more than half of kidney transplant recipients, with a significant impact on graft survival. Recurrence of the primary disease represents the second cause of graft loss after organ rejection. In C3 glomerulopathy, there are several risk factors which can promote a recurrence during transplantation, such as delayed graft function, infection and monoclonal gammopathy. All these events can trigger the alternative complement pathway. In this review, we summarize the impact of C3 glomerulopathy on kidney grafts and present the latest treatment options. The most widely used treatments for the disease include corticosteroids and mycophenolate mofetil, which are already used chronically by kidney transplant recipients; thus, additional treatments for C3 glomerulopathy are required. Currently, several studies using anti-complement drugs (i.e., eculizumab, Ravalizumab, avacopan) for C3 glomerulopathy in kidney transplant patients are ongoing with encouraging results. [ABSTRACT FROM AUTHOR]

Common multi-allelic copy number variants (CNVs) appear enriched for phenotypic associations compared to their biallelic counterparts. Here we investigated the influence of gene dosage effects on adiposity through a CNV association study of gene expression levels in adipose tissue. We identified significant association of a multi-allelic CNV encompassing the salivary amylase gene (AMY1) with body mass index (BMI) and obesity, and we replicated this finding in 6,200 subjects. Increased AMY1 copy number was positively associated with both amylase gene expression (P = 2.31 × 10(-14)) and serum enzyme levels (P < 2.20 × 10(-16)), whereas reduced AMY1 copy number was associated with increased BMI (change in BMI per estimated copy = -0.15 (0.02) kg/m(2); P = 6.93 × 10(-10)) and obesity risk (odds ratio (OR) per estimated copy = 1.19, 95% confidence interval (CI) = 1.13-1.26; P = 1.46 × 10(-10)). The OR value of 1.19 per copy of AMY1 translates into about an eightfold difference in risk of obesity between subjects in the top (copy number > 9) and bottom (copy number < 4) 10% of the copy number distribution. Our study provides a first genetic link between carbohydrate metabolism and BMI and demonstrates the power of integrated genomic approaches beyond genome-wide association studies.