Impaired sense of smell in a Drosophila Parkinson's model.

Parkinson’s disease (PD) is one of the most common neurodegenerative disease characterized by the clinical triad: tremor, akinesia and rigidity. Several studies have suggested that PD patients show disturbances in olfaction at the earliest onset of the disease. The fruit fly Drosophila melanogaster 32 is becoming a powerful model organism to study neurodegenerative diseases. We sought to use this system to explore olfactory dysfunction, if any, in PINK1 mutants, which is a model for PD. PINK1 mutants display many important diagnostic symptoms of the disease such as akinetic motor behavior. In the present study, we describe for the first time, to the best of our knowledge, neurophysiological and neuroanatomical results concerning the olfactory function in PINK1 mutant flies. Electroantennograms were recorded in response to synthetic and natural volatiles (essential oils) from groups of PINK1 mutant adults at three different time points in their life cycle: one from 3-5 day-old flies, from 15-20 and from 27-30 days. The results obtained were compared with the same age-groups of wild type flies. We found that mutant adults showed a decrease in the olfactory response to 1-hexanol, α-pinene and essential oil volatiles. This olfactory response in mutant adults decreased even more as the flies aged. Immunohistological analysis of the antennal lobes in these mutants revealed structural abnormalities, especially in the expression of Bruchpilot protein, a marker for synaptic active zones. The combination of electrophysiological and morphological results suggests that the altered synaptic organization may be due to a neurodegenerative process. Our results indicate that this model can be used as a tool for understanding PD pathogensis and pathophysiology. These results help to explore the potential of using olfaction as a means of monitoring PD progression and developing new treatments

Mucuna pruriens (Velvet bean) Rescues Motor, Olfactory, Mitochondrial and Synaptic Impairment in PINK1(B9) Drosophila melanogaster Genetic Model of Parkinson's Disease

The fruit fly Drosophila melanogaster (Dm) mutant for PTEN-induced putative kinase 1 (PINK1B9) gene is a powerful tool to investigate physiopathology of Parkinson's disease (PD). Using PINK1B9 mutant Dm we sought to explore the effects of Mucuna pruriens methanolic extract (Mpe), a L-Dopa-containing herbal remedy of PD. The effects of Mpe on PINK1B9 mutants, supplied with standard diet to larvae and adults, were assayed on 3–6 (I), 10–15 (II) and 20–25 (III) days old flies. Mpe 0.1% significantly extended lifespan of PINK1B9 and fully rescued olfactory response to 1-hexanol and improved climbing behavior of PINK1B9 of all ages; in contrast, L-Dopa (0.01%, percentage at which it is present in Mpe 0.1%) ameliorated climbing of only PINK1B9 flies of age step II. Transmission electron microscopy analysis of antennal lobes and thoracic ganglia of PINK1B9 revealed that Mpe restored to wild type (WT) levels both T-bars and damaged mitochondria. Western blot analysis of whole brain showed that Mpe, but not L-Dopa on its own, restored bruchpilot (BRP) and tyrosine hydroxylase (TH) expression to age-matched WT control levels. These results highlight multiple sites of action of Mpe, suggesting that its effects cannot only depend upon its L-Dopa content and support the clinical observation of Mpe as an effective medication with intrinsic ability of delaying the onset of chronic L-Dopa-induced long-term motor complications. Overall, this study strengthens the relevance of using PINK1B9 Dm as a translational model to study the properties of Mucuna pruriens for PD treatment

Immune and inflammatory cells in thyroid cancer microenvironment

A hallmark of cancer is the ability of tumor cells to avoid immune destruction. Activated immune cells in tumor microenvironment (TME) secrete proinflammatory cytokines and chemokines which foster the proliferation of tumor cells. Specific antigens expressed by cancer cells are recognized by the main actors of immune response that are involved in their elimination (immunosurveillance). By the recruitment of immunosuppressive cells, decreasing the tumor immunogenicity, or through other immunosuppressive mechanisms, tumors can impair the host immune cells within the TME and escape their surveillance. Within the TME, cells of the innate (e.g., macrophages, mast cells, neutrophils) and the adaptive (e.g., lymphocytes) immune responses are interconnected with epithelial cancer cells, fibroblasts, and endothelial cells via cytokines, chemokines, and adipocytokines. The molecular pattern of cytokines and chemokines has a key role and could explain the involvement of the immune system in tumor initiation and progression. Thyroid cancer-related inflammation is an important target for diagnostic procedures and novel therapeutic strategies. Anticancer immunotherapy, especially immune checkpoint inhibitors, unleashes the immune system and activates cytotoxic lymphocytes to kill cancer cells. A better knowledge of the molecular and immunological characteristics of TME will allow novel and more effective immunotherapeutic strategies in advanced thyroid cancer

Power-assisted pedicle screws placement: Is it as safe and as effective as manual technique? Narrative review of the literature and our technique

Pedicle screws are the gold standard in spine surgery, allowing a solid tricolumnar fixation which is unmatched by hooks and wires. The freehand technique is the most widely adopted for pedicle screws placing. While freehand technique has been classically performed with manual tools, there has been a recent trend toward the use of power tools. The aim of this review is to summarize and expose potential risks and advantages of power pedicle screws placing. The literature showed that the use of power tools offers an acceptable safety profile, comparable to manual technique. With an adequate training, the power technique may speed up the screw placing, reduce the fluoroscopy time and the physical stress to the spine surgeon. Regarding differences in pull-out strength between power and manual techniques, the literature is still uncertain and inconsistent, both in clinical and preclinical studies. The choice between the use of power and manual freehand pedicle screws placing is still based on the surgeon’s own preference

Adipose-derived stem cells applied to ankle pathologies: a systematic review

: The purpose of this systematic review was to analyze the current use of adipose-derived mesenchymal stem cells (ADMSCs) and present the available evidence on their therapeutic potential in the treatment of ankle orthopedic issues, evaluating the applications and results. A literature search of PubMed, Google Scholar, EMBASE and Cochrane Library database was performed. The review was conducted following PRISMA guidelines. Risk of bias assessment was conducted through the Methodological Index for Non-Randomized Studies (MINORS) criteria. Initial search results yielded 4348 articles. A total of 8 articles were included in the review process. No clinical evidence has demonstrated the effectiveness of one isolation method over the other, but nonenzymatic mechanical method has more advantages. In all studies included significant clinical outcomes improvement were recorded in patients affected by osteochondral lesion and osteoarthritis of ankle. All studies performed a concomitant procedure. No serious complications were reported. ADMSC injection, especially through the nonenzymatic mechanical methods, looks to be simple and promising treatment for osteochondral lesions and osteoarthritis of the ankle, with no severe complications. The current scarcity of studies and their low-quality level preclude definitive conclusions presently. LEVEL OF EVIDENCE: III

Thyroid autoimmune disorders and cancer

In the last decades, many studies conducted in vitro, and in vivo, have shown that thyroid autoimmunity and thyroid cancer (TC) (mainly papillary TC) can be concomitant, even if the exact mechanisms at the basis of this association are still not clear. Growing incidence of TC coincides with increased registration of autoimmune thyroid disorders (AITD) suggesting an association between those pathologies. Elevated TSH levels and thyroid autoimmunity were defined as independent risk factors for TC. However a lot of evidence suggests that autoimmunity and inflammation, per se, are risk factors for TC. The link between inflammation and TC involves multiple components of the immune system, extracellular matrix, stroma, and adipose tissue, with pro-tumoral activity of inflammation being opposed to anti-inflammatory effects, favoring protection against cancer progression. Within the tumor microenvironment, inflammatory cells, belonging both to innate (macrophages) and adaptive (lymphocytes) immune responses, are interconnected with fibroblasts, endothelial cells, adipocytes, and extracellular matrix through cytokines, chemokines and adipocytokines. Under the influence of transcriptional regulators (such as Nuclear Factor-kappa B, mitogen-activated protein kinases, or Phosphoinositide-3 kinase/protein kinase-B), oncogenes connected to the different subtypes of TC promote their farthermost proliferative effect on the tumor microenvironment. Future studies will be necessary to understand the connections between thyroid autoimmunity and cancer, also in order to design a tailored therapy for TC patients with AITD

Freehand power-assisted pedicle screw placement in scoliotic patients: results on 5522 consecutive pedicle screws

Pedicle screws is the current gold standard in spine surgery, achieving a solid tricolumnar fixation which is unreachable by wires and hooks. The freehand technique is the most widely adopted for pedicle screws placing. While freehand technique has been classically performed with manual tools, there has been a recent trend toward the use of power tools. However, placing a pedicle screw remains a technically demanding procedure with significant risk of complications. The aim of this article is to retrospectively evaluate safety and accuracy of free-hand power-assisted pedicle screw placement in a cohort of patients who underwent correction and fusion surgery for scoliosis (both idiopathic and non-idiopathic) in our department. A retrospective review of all patients with scoliosis who underwent surgery and received a postoperative CT scan in our department in a 9-year period was undertaken. Screw density, number and location of pedicle screws were measured using pre and postoperative full-length standing and lateral supine side-bending radiographs. Then, postoperative CT scan was used to assess the accuracy of screw placement according to Gertzbein-Robbins scale. Malpositioned screws were divided according to their displacement direction. Finally, intra and postoperative neurological complications and the need for revision of misplaced screws were recorded. A total of 205 patients were included, with a follow-up of 64.9 ± 38.67 months. All constructs were high density (average density 1.97 ± 0.04), and the average number of fusion levels was 13.72 ± 1.97. A total of 5522 screws were placed: 5308 (96.12%) were grade A, 141 (2.5%) grade B, 73 (1.32%) grade C. Neither grade D nor grade E trajectories were found. The absolute accuracy (grade A) rate was 96.12% (5308/5522) and the effective accuracy (within the safe zone, grade A + B) was 98.6% (5449/5522). Of the 73 misplaced screws (grade C), 59 were lateral (80.80%), 8 anterior (10.95%) and 6 medial (8.22%); 58 were in convexity, while 15 were in concavity (the difference was not statistically significant, p = 0.33). Intraoperatively, neither neurological nor vascular complications were recorded. Postoperatively, 4 screws needed revision (0.072% of the total): Power-assisted pedicle screw placing may be a safe an accurate technique in the scoliosis surgery, both of idiopathic and non-idiopathic etiology. Further, and higher quality, research is necessary in order to better assess the results of this relatively emerging technique

Epigenetic and Genetic Factors Related to Curve Progression in Adolescent Idiopathic Scoliosis: A Systematic Scoping Review of the Current Literature

Adolescent idiopathic scoliosis (AIS) is a progressive deformity of the spine. Scoliotic curves progress until skeletal maturity leading, in rare cases, to a severe deformity. While the Cobb angle is a straightforward tool in initial curve magnitude measurement, assessing the risk of curve progression at the time of diagnosis may be more challenging. Epigenetic and genetic markers are potential prognostic tools to predict curve progression. The aim of this study is to review the available literature regarding the epigenetic and genetic factors associated with the risk of AIS curve progression. This review was carried out in accordance with Preferential Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The search was carried out in January 2022. Only peer-reviewed articles were considered for inclusion. Forty studies were included; fifteen genes were reported as having SNPs with significant association with progressive AIS, but none showed sufficient power to sustain clinical applications. In contrast, nine studies reporting epigenetic modifications showed promising results in terms of reliable markers. Prognostic testing for AIS has the potential to significantly modify disease management. Most recent evidence suggests epigenetics as a more promising field for the identification of factors associated with AIS progression, offering a rationale for further investigation in this field

Diagnosis and treatment of acute inflammatory sacroiliitis in pregnant or post-partum women: a systematic review of the current literature

: The aim of the present study is to systematically review the current literature about diagnosis and treatment of acute inflammatory sacroiliitis in pregnant or post-partum women. A systematic search was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data about clinical presentation, diagnosis methods and treatment strategies were retrieved from included studies and reported in a table. After screening, five studies on 34 women were included; they were all affected by acute inflammatory sacroiliitis. Clinical examination and magnetic resonance imaging were used to confirm diagnosis. In four studies, patients were treated with ultrasound-guided sacroiliac injections of steroids and local anesthetics, while one study used only manual mobilization. Clinical scores improved in all patients. Ultrasound-guided injections proved to be a safe and effective strategy for inflammatory sacroiliitis treatment during pregnancy or post-partum