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Background: Managing vertebral metastases (VM) is still challenging in oncology, necessitating the use of effective surgical strategies to preserve patient quality of life (QoL). Traditional open posterior fusion (OPF) and percutaneous osteosynthesis (PO) are well-documented approaches, but their comparative efficacy remains debated. Methods: This retrospective study compared short-term outcomes (6–12 months) between OPF and PO in 78 cancer patients with spinal metastases. This comprehensive evaluation included functional, clinical, and radiographic parameters. Statistical analysis utilized PRISM software (version 10), with significance set at p < 0.05. Results: PO demonstrated advantages over OPF, including shorter surgical durations, reduced blood loss, and hospital stay, along with lower perioperative complication rates. Patient quality of life and functional outcomes favored PO, particularly at the 6-month mark. The mortality rates at one year were significantly lower in the PO group. Conclusions: Minimally invasive techniques offer promising benefits in VM management, optimizing patient outcomes and QoL. Despite limitations, this study advocates for the adoption of minimally invasive approaches to enhance the care of multi-metastatic patients with symptomatic VM.

Background: Among aneuploidies compatible with life, trisomy 22 mosaicism is extremely rare, and only about 25 postnatal and 18 prenatal cases have been described in the literature so far. The condition is mainly characterized by facial and body asymmetry, cardiac heart defects, facial dysmorphisms, growth failure, delayed puberty, and variable degrees of neurodevelopmental delay. Problem: The scattered information regarding the condition and the dearth of data on its natural history and developmental outcomes restrict genetic counseling, particularly in prenatal settings. Moreover, a prompt diagnosis is frequently delayed by the negative selection of trisomic cells in blood, with mosaicism percentage varying among tissues, which often entails the need for further testing. Purpose/topic: The aim of our work is to provide assistance in prenatal and postnatal genetic counseling by systematically delineating the current knowledge of the condition. This entails defining the prenatal and postnatal characteristics of the condition and presenting novel data from three cases, both prenatally and postnatally. Additionally, we report the developmental outcomes observed in two new patients.

Background: Adolescent idiopathic scoliosis (AIS) is a spinal pathology affecting 0.47–5.2% of the population, often requiring surgical intervention to control deformity progression. Posterior spinal instrumentation and fusion with pedicle screw fixation are standard procedures for AIS curve correction; however, implant failure remains a significant complication, especially in multi-level fusions. This retrospective cohort study aims to compare the failure rates between conventional pedicle screws (CPSs) and fenestrated pedicle screws (FPSs) in AIS treatment, with a focus on investigating potential causes of these failures. Methods: This study, conducted from January 2016 to December 2020, involves a two-center retrospective analysis of AIS patients undergoing posterior instrumented fusion. Results: Data from a total of 162 patients (122 females and 40 males) revealed a mean age of 14.95 years (range: 11–18). The CPS group consisted of 80 patients (56 females and 24 males), whereas the FPS group consisted of 82 patients (66 females and 16 males) stratified by Risser grade and Lenke Classification. Radiological assessments, clinical outcomes, and SRS-22 scores were evaluated pre-operatively, at 6 months, and post-operatively (minimum follow-up of 2 years). Conclusions: Fenestrated pedicle screws (FPSs) pose concerns due to their lower mechanical strength compared to solid screws. Understanding their limitations and optimizing their application in AIS treatment is essential.

Mutations in CSA and CSB proteins cause Cockayne syndrome, a rare genetic neurodevelopment disorder. Alongside their demonstrated roles in DNA repair and transcription, these two proteins have recently been discovered to regulate cytokinesis, the final stage of the cell division. This last finding allowed, for the first time, to highlight an extranuclear localization of CS proteins, beyond the one already known at mitochondria. In this study, we demonstrated an additional role for CSA protein being recruited at centrosomes in a strictly determined step of mitosis, which ranges from pro-metaphase until metaphase exit. Centrosomal CSA exerts its function in specifically targeting the pool of centrosomal Cyclin B1 for ubiquitination and proteasomal degradation. Interestingly, a lack of CSA recruitment at centrosomes does not affect Cyclin B1 centrosomal localization but, instead, it causes its lasting centrosomal permanence, thus inducing Caspase 3 activation and apoptosis. The discovery of this unveiled before CSA recruitment at centrosomes opens a new and promising scenario for the understanding of some of the complex and different clinical aspects of Cockayne Syndrome.

Abstract Background Diagnostic criteria are not always useful to discriminate major depression with anxious distress (ADS-D; Diagnostic and Statistical Manual for Mental Disorders, version-5 [DSM-5] criteria) from mixed depression (Koukopoulos’ criteria; KMX-D). So, clinicians need alternative tools to improve their diagnostic ability and to choose the most appropriate treatment. The aim of the present study is to identify socio-demographic and clinical features that discriminate patients with ADS-D from those with KMX-D. Methods Two hundred and forty-one consecutive outpatients with unipolar (51%) and bipolar (49%) disorder, fulfilling DSM-5 criteria for a current major depressive episode (MDE) and with a 21-item Hamilton Depression Rating Scale score ≥ 14, were recruited and treated in a prospective observational study. Results Ten percent of patients met criteria for KMX-D, 22% ADS-D, and 37% for both. Irritable premorbid temperament, mixed depression polarity at onset, mixed depression recurrence, and a high number of mania symptoms at intake were typical features of patients with KMX-D. Depressive polarity at onset, a low number of mania symptoms at intake, and generalized anxiety disorder comorbidity were typical features of patients with ADS-D. Multinomial logistic regression confirmed that higher rate of irritable temperament and higher Young Mania Rating Scale total score differentiated patients with KMX-D from patients with pure MDE. Conclusion Our findings suggest some clinical features that could help differentiate between ADS-D and KMX-D in patients meeting both conditions and to select the appropriate treatment. However, the small sample size may have limited the power to detect differences between the groups. Further research is needed to confirm the results of present study.

Abstract Background Adult spinal deformities (ASD) represent a growing clinical condition related to chronic pain, disability and reduction in quality of life (QoL). A strong correlation among spinal alignment, spinopelvic parameters and QoL after spinal fusion surgery in ASD patients was thoroughly investigated over the last decade, However, only few studies focused on the relationship between lumbo-pelvic-femoral parameters - such as Femoral Obliquity Angle (FOA), T1 Pelvic Angle (TPA) and QoL. Methods Radiological and clinical data from 43 patients surgically treated with thoracolumbar posterior spinal fusion for ASD between 2015 and 2018 were retrospectively analyzed. The primary outcomes were the correlation between preoperative spino-pelvic-femoral parameters and postoperative clinical, functional outcomes and QoL. Secondary outcomes were: changes in sagittal radiographic parameters spino-pelvic-femoral, clinical and functional outcomes and the rate of complications after surgery. Results Using Spearman’s rank correlation coefficients, spinopelvic femoral parameters (FOA, TPA, pre and post-operative) are directly statistically correlated to the quality of life (ODI, SRS-22, pre and post-operative; > 0,6 strong correlation, p

DNA repair genes are critical for preserving genomic stability and it is well established that mutations in DNA repair genes give rise to progeroid diseases due to perturbations in different DNA metabolic activities. Cockayne Syndrome (CS) is an autosomal recessive inheritance caused by inactivating mutations in CSA and CSB genes. This review will primarily focus on the two Cockayne Syndrome proteins, CSA and CSB, primarily known to be involved in Transcription Coupled Repair (TCR). Curiously, dysregulated expression of CS proteins has been shown to exhibit differential health outcomes: lack of CS proteins due to gene mutations invariably leads to complex premature aging phenotypes, while excess of CS proteins is associated with carcinogenesis. Thus it appears that CS genes act as a double-edged sword whose loss or gain of expression leads to premature aging and cancer. Future mechanistic studies on cell and animal models of CS can lead to potential biological targets for interventions in both aging and cancer development processes. Some of these exciting possibilities will be discussed in this review in light of the current literature.

Musculoskeletal disorders are among the leading causes of disability and chronic pain worldwide, and their impact is expected to increase in the coming years [...]

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, characterized by an initial and progressive loss of dopaminergic neurons of the substantia nigra pars compacta via a potentially substantial contribution from protein aggregates, the Lewy bodies, mainly composed of α-Synuclein among other factors. Distinguishing symptoms of PD are bradykinesia, muscular rigidity, unstable posture and gait, hypokinetic movement disorder and resting tremor. Currently, there is no cure for PD, and palliative treatments, such as Levodopa administration, are directed to relieve the motor symptoms but induce severe side effects over time. Therefore, there is an urgency for discovering new drugs in order to design more effective therapeutic approaches. The evidence of epigenetic alterations, such as the dysregulation of different miRNAs that may stimulate many aspects of PD pathogenesis, opened a new scenario in the research for a successful treatment. Along this line, a promising strategy for PD treatment comes from the potential exploitation of modified exosomes, which can be loaded with bioactive molecules, such as therapeutic compounds and RNAs, and can allow their delivery to the appropriate location in the brain, overcoming the blood–brain barrier. In this regard, the transfer of miRNAs within Mesenchymal stem cell (MSC)-derived exosomes has yet to demonstrate successful results both in vitro and in vivo. This review, besides providing a systematic overview of both the genetic and epigenetic basis of the disease, aims to explore the exosomes/miRNAs network and its clinical potential for PD treatment.

BackgroundSurgical palliative treatment of spinal metastases (SM) could influence the quality of life (QoL) in cancer patients, since the spine represents the most common site of secondary bony localization. Traditional open posterior instrumented fusion (OPIF) and Percutaneous pedicle screw fixation (PPSF) became the main surgical treatment alternatives for SM, but in Literature there is no evidence that describes the absolute superiority of one treatment over the other.Materials and MethodsThis is a systematic review and meta-analysis of comparative studies on PPSF versus OPIF in patients with SM, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The outcomes of interest were: complications, blood loss, infections, mortality, pain and also the Quality of Life (QoL).ResultsThere were a total of 8 studies with 448 patients included in the meta-analyses. Postoperative complications were more frequent in OPIF (odds ratio of 0.48. 95% CI, 0.27 to 0.83; p= 0.01), PPFS was associated with blood loss (odds ratio -585.70. 95% IC, -848.28 to -323.13.69; p< 0.0001) and a mean hospital stay (odds ratio -3.77. 95% IC, -5.92 to -1.61; p= 0.0006) decrease. The rate of infections was minor in PPFS (odds ratio of 0.31. 95% CI, 0.12 to 0.81; p= 0.02) whereas the occurrence of reinterventions (0.76. 95% CI, 0.25 to 2.27; p= 0.62) and the mortality rate was similar in both groups (odds ratio of 0.79. 95% CI, 0.40 to 1.58; p= 0.51). Finally, we also evaluated pre and post-operative VAS and the meta-analysis suggested that both techniques have a similar effect on pain.Discussion and ConclusionThe PPSF treatment is related with less complications, a lower rate of infections, a reduction in intraoperative blood loss and a shorter hospital stay compared to the OPIF treatment. However, further randomized clinical trials could confirm the results of this meta-analysis and provide a superior quality of scientific evidence.

Objective Vertebral aspergillosis is quite rare conditions, often misdiagnosed, that requires long-term antibiotic therapy, and sometimes, surgical treatments. The present investigations were aimed to investigate the epidemiology, clinical-radiological aspects, treatment protocols, and outcomes of Aspergillus-mediated vertebral osteomyelitis. Methods A systematic review of the pertinent English literature according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was performed. The research was conducted on Cochrane library, MEDLINE, PubMed, and Scopus using as search-terms “Aspergillus,” “vertebral osteomyelitis,” “spondylodiscitis,” “spine infection.” A case of vertebral aspergillosis conservatively managed was also reported. Results Eighty-nine articles were included in our systematic review. Including the reported case, our analysis covered 112 cases of vertebral aspergillosis. Aspergillus fumigatus was isolated in 68 cases (61.2%), Aspergillus flavus in 14 (12.6%), Aspergillus terreus in 4 (3.6%), Aspergillus nidulans in 2 (1.8%). Seventy-three patients (65.7%) completely recovered at the last follow-up evaluation; in 7 patients (6.3%) radiological signs of chronic infection were reported, whereas 32 patients (28.8%) died during the follow-up. Conclusion This systematic review summarized the state of the art on vertebral aspergillosis, retrieving data on clinical features, diagnostic criteria and current limitations, treatment alternatives, and their outcomes.

The serine/threonine kinase Akt modulates the functions of numerous substrates, many of them being involved in cell proliferation and growth, metabolism, angiogenesis, resistance to hypoxia and migration. Akt is frequently deregulated in many types of human cancers, its overexpression or abnormal activation being associated with the increased proliferation and survival of cancer cells. A promising avenue for turning off the functionality of Akt is to either interfere with the K63-linked ubiquitination that is necessary for Akt membrane recruitment and activation or increase the K48-linked polyubiquitination that aims to target Akt to the proteasome for its degradation. Recent evidence indicates that targeting the ubiquitin proteasome system is effective for certain cancer treatments. In this review, the functions and roles of Akt in human cancer will be discussed, with a main focus on molecules and compounds that target various elements of the ubiquitination processes that regulate the activation and inactivation of Akt. Moreover, their possible and attractive implications for cancer therapy will be discussed.

Background: Complex regional pain syndrome (CRPS) is a postoperative, misdiagnosed condition highlighted only by pain therapists after numerous failed attempts at pain control by the treating surgeon in the case of prolonged pain after surgery. It only occurs rarely after spine surgery, causing the neurosurgeon’s inappropriate decision to resort to a second surgical treatment. Methods: We performed a systematic review of the literature reporting and analyzing all recognized and reported cases of CRPS in patients undergoing spinal surgery to identify the best diagnostic and therapeutic strategies for this unusual condition. We compare our experience with the cases reported through a review of the literature. Results: We retrieve 20 articles. Most of the papers are clinical cases showing the disorder’s rarity after spine surgery. Most of the time, the syndrome followed uncomplicated lumbar spine surgery involving one segment. The most proposed therapy was chemical sympathectomy and spinal cord stimulation. Conclusion: CRPS is a rare pathology and is rarer after spine surgery. However, it is quite an invalidating disorder. Early therapy and resolution, however, require a rapid diagnosis of the syndrome. In our opinion, since CRPS occurs relatively rarely following spinal surgery, it should not have a substantial impact on the indications for and timing of these operations. Therefore, it is essential to diagnose this rare occurrence and treat it promptly and appropriately.

Background: Due to the COVID-19 pandemic outbreak, many changes were done in the hospital practice, and new guidelines were issued in order to contain the infection spread. One of the most common measures is represented by a correct and frequent hand washing. Recently, an association between increased adherence to hand hygiene (HH) protocols and reduction in hospital infections was documented however no studies about the surgical wound infection rate were reported in the Literature. Methods: The present study represents a multicentric retrospective epidemiological study. The HH compliance rate was recorded through direct observations by trained nurses, 24 h a day. The primary outcome was HH compliance rate. The association of HH with spinal surgical wound infections was the secondary outcome. Results: We reported a compliance to HH practices during the pandemic period of 85.2% compared with 57% observed during 2019. Our analysis showed an overall surgical wound infection reduction of 66.6% during the hospital stay in the pandemic period. Conclusion: Hand hygiene has always been considered one of the most effective, reproducible and low-cost weapons to deal with hospital infections. The good health habits acquired during the COVID-19 pandemic should be maintained even after the virus is eradicated.

Breast cancer (BC) is the most common cancer with the highest frequency of death among women. BC is highly heterogenic at the genetic, biological, and clinical level. Despite the significant improvements in diagnosis and treatments of BC, the high rate of cancer recurrence and resistance to treatment remains a major challenge in clinical practice. This issue is particularly relevant in Triple-Negative Breast Cancer (TNBC) subtype, for which chemotherapy remains the main standard therapeutic approach. Here, we observed that BC cells, belonging to different subtypes, including the TNBC, display an increased expression of Cockayne Syndrome group A (CSA) protein, which is involved in multiple functions such as DNA repair, transcription, mitochondrial homeostasis, and cell division and that recently was found to confer cell robustness when it is up-regulated. We demonstrated that CSA ablation by AntiSense Oligonucleotides (ASOs) drastically impairs tumorigenicity of BC cells by hampering their survival and proliferative capabilities without damaging normal cells. Moreover, suppression of CSA dramatically sensitizes BC cells to platinum and taxane derivatives, which are commonly used for BC first-line therapy, even at very low doses not harmful to normal cells. Finally, CSA ablation restores drug sensitivity in oxaliplatin-resistant cells. Based on these results, we conclude that CSA might be a very attractive target for the development of more effective anticancer therapies.

Risperidone is a safe second-generation antipsychotic which is rarely associated with the emergence of a few adverse effects, such as oral lesions and stomatitis. We report the case of a 77-year-old woman affected by a neurocognitive disorder with psychotic features and treated with risperidone 2 mg/day. After 1 week, she showed a burning mouth syndrome with oral lesions and risperidone was discontinued. Antipsychotic-induced oral ulcerations may be caused by the reduction of saliva protection with minor adverse effects related to oral movement disorders or impairment of the bacterial flora of saliva.

Total hip arthroplasty (THA) is considered the most successful orthopedic surgical procedure of the last century with excellent survivorship up to 20-years. However, instability remains a major issue representing the most common reason for revision after THA. Hip-spine relationship has gained progressive interest between arthroplasty surgeons and its understanding is crucial in order to identify high-risk patients for postoperative dislocation. Spinal deformity and abnormal spinopelvic mobility have been associated with increased risk for instability, dislocation and revision THA. Preoperative workup begins with standing anteroposterior pelvis x-ray and lateral spinopelvic radiographs in the standing and sitting position. Hip-spine stiffness needs to be addressed before THA in consideration of adapting the preoperative planning to the patient’s characteristics. Acetabular component should be implanted with different anteversion and inclination angles according to the pattern of hip-spine motion in order to reduce the risk of impingement and consequent dislocation. Different algorithmic approaches have been proposed in case of concomitant hip-spine disease and in case of altered sagittal balance and pelvic mobility. The aim of this review is to investigate and clarify the hip-spine relationships and evaluate the impact on modern total hip arthroplasty.

Vertebral Hemangioma (VH) is a benign tumor usually symptomless and discovered incidentally. Pregnancy, because of several hormonal and physiologic changes, is a recognized risk factor coinciding with the development of a rapid onset of neurological symptoms in patients affected by VH. In the Literature, sporadic cases of neurological symptoms have been described, which occurred during pregnancy, but only rarely the onset of symptoms was reported after pregnancy and childbirth. Usually surgical treatment is reserved for severe cases with rapid onset of neurological symptoms. However, the use of conservative treatments is still a topic of debate In the present study, we report a series of patients affected by VH become symptomatic during or after pregnancy along with a systematic review of the Literature.

Back Pain (BP) is a common medical problem; anabolic hormones, through the modulation of oxidative stress (OS), could influence fracture risk. We evaluated the prevalence of anabolic hormonal deficiencies and their relationship with OS in males with BP, associated or not to nontraumatic fractures. 49 males with BP, from 36 to 80 years, were divided in two groups according to radiological evidence of nontraumatic fractures; group A (n=25): non-fractured; group B (n=24): fractured. A different prevalence of hormonal deficits was observed: 24% of hypotestosteronemia in A, 0% in B; 16% of GHD in A, 29% in B; Total Antioxidant Capacity (TAC) showed a trend toward higher levels in B. In A, despite lower TAC, a significant inverse correlation was present between TAC and IGF-1. A greater prevalence of GHD in patients with vertebral fractures was seen and, in a subgroup, OS could mediate the deleterious effects of hyposecretory GH state.

Spinal epidural hematoma (SEH) is a rare cause of nerve root or cord compression; its pathogenesis is not always clearly recognizable. The aim of this paper was to investigate possible etiopathological factors in a consecutive series of patients affected by traumatic SEH treated at our institution. Seven patients with neurologic impairment due to traumatic SEH were retrospectively analyzed after diagnosis and surgical treatment. Thoracic localization was found in 5 cases, and lumbar and cervical localization were found in 1 patient each. One patient was affected by ankylosing spondylitis and one by diffuse idiopathic skeletal hyperostosis. SEH was associated with spine fractures in 6 cases. Only 2 cases of traumatic SEH resulted from high-energy trauma. All patients underwent surgical decompression within 24 hours after admittance to the hospital. Three patients recovered completely, 3 remained paraplegic, and 1 remained monoplegic. Several concomitant conditions are suggested to be predisposing factors for the development of SEH, although its inherent mechanism is still unknown. Two patients in the present series were affected by rheumatologic disorders, confirming the elevated incidence of hematomas in such patients compared to the normal population. Three very unusual cases of SEH occurred in senile patients affected by osteoporotic fractures. Early diagnosis and urgent decompression of the hematoma remain mandatory.

Neuroblastoma, the most common extra-cranial solid tumor of early childhood, is one of the major therapeutic challenges in child oncology: it is highly heterogenic at a genetic, biological, and clinical level. The high-risk cases have one of the least favorable outcomes amongst pediatric tumors, and the mortality rate is still high, regardless of the use of intensive multimodality therapies. Here, we observed that neuroblastoma cells display an increased expression of Cockayne Syndrome group B (CSB), a pleiotropic protein involved in multiple functions such as DNA repair, transcription, mitochondrial homeostasis, and cell division, and were recently found to confer cell robustness when they are up-regulated. In this study, we demonstrated that RNAi-mediated suppression of CSB drastically impairs tumorigenicity of neuroblastoma cells by hampering their proliferative, clonogenic, and invasive capabilities. In particular, we observed that CSB ablation induces cytokinesis failure, leading to caspases 9 and 3 activation and, subsequently, to massive apoptotic cell death. Worthy of note, a new frontier in cancer treatment, already proved to be successful, is cytokinesis-failure-induced cell death. In this context, CSB ablation seems to be a new and promising anticancer strategy for neuroblastoma therapy.

A series of N-((3-phenyl-1-(phenylsulfonyl)-1H-pyrazol-4-yl)methyl)anilines 7a-p and 8a-l, structurally related to previously synthesized and tested (N-(1,3-diphenyl-1H-pyrazol-4-yl)methyl)anilines (1a-v), were designed and synthesized. The new derivatives were evaluated in cell-based assays for their cytotoxicity and antiviral activity against a large panel of RNA and DNA viruses of public health significance. Generally, the tested compounds did not display cytotoxicity toward the cell lines used. The majority of derivatives 7a-p were able to interfered with YFV and RSV replication in the micromolar range showing a marked improvement in potency and selectivity with respect to the reference inhibitors 6-azauridine and ribavirin, respectively. The introduction of a p-methoxy substituent on the phenylsulfonyl group (compounds 8a-l) completely abolished the anti-RSV activity and reduced or eliminated the potency against YFV. On the contrary, several p-methoxy analogs were able to interfere with BVDV replication with a comparable (8b, 8c, 8g, and 8k) or better (8a and 8f) potency than the reference inhibitor, ribavirin. Compound 7e, selected for time of addition experiments on BHK-21 cell cultures infected with YFV, achieved the highest reduction of virus titer when added 2 h post infection and maintained up to 4 h post infection.

Hypochondriasis (HYPO), an obsessive-compulsive spectrum disorder, is frequent in patients with schizophrenia (SCH) (20%), especially among those treated with clozapine (36.7%). Treatment options for OCS/OCD in patients under clozapine (CLZ) include combining clozapine with amisulpride/aripiprazole or a mood stabilizer, augmenting clozapine with a serotoninergic reuptake inhibitor, adding cognitive behavioural therapy, and gradually reducing dosage. No treatments have been proposed for HYPO in patients using clozapine so we examine these options in 2 cases and report the results. Among treatments delivered, only dosage reduction adequately worked. We recommend caution when thinking about escalating treatment and suggest trying it only when alternative interventions were not successful and weighing risk and benefits of this therapeutic strategy. Further research is needed to confirm the hypothesis that CLZ treatment induces hypochondriac symptoms, to investigate the prevalence of the phenomenon, and, mostly, to identify possible treatment strategies.

The DNA repair protein Cockayne syndrome group B (CSB) has been recently identified as a promising anticancer target. Suppression, by antisense technology, of this protein causes devastating effects on tumor cells viability, through a massive induction of apoptosis, while being non-toxic to non-transformed cells. To gain insights into the mechanisms underlying the pro-apoptotic effects observed after CSB ablation, global gene expression patterns were determined, to identify genes that were significantly differentially regulated as a function of CSB expression. Our findings revealed that response to endoplasmic reticulum stress and response to unfolded proteins were ranked top amongst the cellular processes affected by CSB suppression. The major components of the endoplasmic reticulum stress-mediated apoptosis pathway, including pro-apoptotic factors downstream of the ATF3-CHOP cascade, were dramatically up-regulated. Altogether our findings add new pieces to the understanding of CSB mechanisms of action and to the molecular basis of CS syndrome.

Lamin family proteins are structural components of a filamentous framework, the nuclear lamina (NL), underlying the inner membrane of nuclear envelope. The NL not only plays a role in nucleus mechanical support and nuclear shaping, but is also involved in many cellular processes including DNA replication, gene expression and chromatin positioning. Spermatogenesis is a very complex differentiation process in which each stage is characterized by nuclear architecture dramatic changes, from the early mitotic stage to the sperm differentiation final stage. Nevertheless, very few data are present in the literature on the NL behavior during this process. Here we show the first and complete description of NL behavior during meiosis and spermatogenesis in Drosophila melanogaster. By confocal imaging, we characterized the NL modifications from mitotic stages, through meiotic divisions to sperm differentiation with an anti-laminDm0 antibody against the major component of the Drosophila NL. We observed that continuous changes in the NL structure occurred in parallel with chromatin reorganization throughout the whole process and that meiotic divisions occurred in a closed context. Finally, we analyzed NL in solofuso meiotic mutant, where chromatin segregation is severely affected, and found the strict correlation between the presence of chromatin and that of NL.

The CSB protein, a member of the SWI/SNF ATP dependent chromatin remodeling family of proteins, plays a role in a sub-pathway of nucleotide excision repair (NER) known as transcription coupled repair (TCR). CSB is frequently mutated in Cockayne syndrome group B, a segmental progeroid human autosomal recessive disease characterized by growth failure and degeneration of multiple organs. Though initially classified as a DNA repair protein, recent studies have demonstrated that the loss of CSB results in pleiotropic effects. Identification of novel proteins belonging to the CSB interactome may be useful not only for predicting the molecular basis for diverse pathological symptoms of CS-B patients but also for unraveling the functions of CSB in addition to its authentic role in DNA repair. In this study, we performed tandem affinity purification (TAP) technology coupled with mass spectrometry and co-immunoprecipitation studies to identify and characterize the proteins that potentially interact with CSB-TAP. Our approach revealed 33 proteins that were not previously known to interact with CSB. These newly identified proteins indicate potential roles for CSB in RNA metabolism involving repression and activation of transcription process and in the maintenance of chromatin dynamics and integrity.

Previous research has reported that a functional polymorphism in the monoamine oxidase A (MAOA) gene promoter can moderate the association between early life adversity and increased risk for violence and antisocial behavior. In this study of a combined population of psychiatric outpatients and healthy volunteers (N = 235), we tested the hypothesis that MAOA genotype moderates the association between early traumatic life events (ETLE) experienced during the first 15 years of life and the display of physical aggression during adulthood, as assessed by the Aggression Questionnaire. An ANOVA model including gender, exposure to early trauma, and MAOA genotype as between-subjects factors showed significant MAOAxETLE (F(1,227) = 8.20, P = 0.005) and genderxMAOAxETLE (F(1,227) = 7.04, P = 0.009) interaction effects. Physical aggression scores were higher in men who had experienced early traumatic life events and who carried the low MAOA activity allele (MAOA-L). We repeated the analysis in the subgroup of healthy volunteers (N = 145) to exclude that the observed GxE interactions were due to the inclusion of psychiatric patients in our sample and were not generalizable to the population at large. The results for the subgroup of healthy volunteers were identical to those for the entire sample. The cumulative variance in the physical aggression score explained by the ANOVA effects involving the MAOA polymorphism was 6.6% in the entire sample and 12.1% in the sub-sample of healthy volunteers. Our results support the hypothesis that, when combined with exposure to early traumatic life events, low MAOA activity is a significant risk factor for aggressive behavior during adulthood and suggest that the use of dimensional measures focusing on behavioral aspects of aggression may increase the likelihood of detecting significant gene-by-environment interactions in studies of MAOA-related aggression.