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Background Granulicatella adiacens is a nutritional variant of streptococcus (NVS), which has been rarely reported as an etiologic agent in spondylodiscitis (SD). Material and methods We report a case of a 51-year-old male with from chronic low-back pain associated with right sciatica and ipsilateral monoparesis. Spinal MRI showed radiological signs on L1-L2 and L5-S1 discs consistent with SD. We also performed a systematic review of the pertinent literature in order to retrieve all the key information regarding microbiological and clinical features. Results Including our patients, seven cases with a mean age 56 ± 10.2 years were reported in English literature. Six patients were conservatively managed with antibiotic therapy (66%), whereas three with surgery in combination with antibiotics (33%). An endocarditis was associated in three cases, and a pacemaker infection in one. All patients received targeted antibiotic therapy resulting in a quick improvement of clinical symptoms with favorable outcome. Our case is the only with a skip spontaneous SD, which needed a surgical decompression due to the associated neurological symptoms. Conclusions This incidence of SD sustained by Granulicatella adiances could be underestimated due to their particular microbiological conditions requested for their cultures. However, this infection should be suspected in cases of culture-negative SD, especially when associated with endocarditis.

Pharyngoesophageal injury during anterior cervical spine surgery is a rare and potentially life-threatening complication; generally it is the result of intraoperative manipulation or hardware erosion and sometimes may be due to weakness of the pharyngoesophageal wall from pre-existing pathologic conditions, such as diabetes, gastritis, or obesity.We describe the management strategies in patients with an early postoperative hypopharyngeal perforation that occurred after anterior cervical spine surgery without failure of instrumentation, and we present a case treated endoscopically at our institution.Appropriate treatment for pharyngoesophageal perforations is controversial and not investigated in detail. There is a lack of prospective studies comparing initial conservative versus surgical approaches to treatment. In addition, endoscopic management is growing as a therapeutic option, but no consensus concerning the indications for an endoscopic approach in the treatment of pharyngoesophageal injury in anterior cervical spine surgery is currently reached. A common theme proposed in the literature is that early recognition and aggressive investigation and treatment are essential to ensure a good outcome. A customized interdisciplinary surgical approach is essential for successful treatment. Use of the transoral endoscopic approach is a useful noninvasive method to treat this rare but potentially devastating complication.

Spine deformities could be considered a possible manifestation of the childhood hypotonia, typical feature of Kleefstra Syndrome (KS). There is a paucity of literature describing posterior spinal fusion in the Kleefstra syndrome patient. For patients who develop severe scoliotic curve, bracing is often ineffective and surgery is recommended. We report the first corrective surgery for scoliosis in one patient with KS. We describe a case of 13-year-old female with severe developmental scoliosis in KS. Preoperative examination showed a thoracolumbar scoliosis with left convex thoracic curve (T3-T9, 97°) and right convex thoracolumbar curve (T9-L3, 88°). Posterior correction, pedicle screw fixation and bone graft fusion T3-L5 was performed. Postoperatively, the thoracic curve was corrected to 33° while the thoracolumbar one to 26° and better standing posture was obtained. Six month follow-up images showed no loosening of the hardware. The patient is still in our follow-up program. Scoliosis seems to be a rare evenience of the severe hypotonia of patients with KS. We report the first case of scoliosis in KS treated successfully with surgery. Corrective surgery for spinal deformity, such as scoliosis, could help in posture and improve the quality of life especially in complicated patients such as syndromic ones.

Telomere shortening has been supposed to be implicated in both aging and various human diseases es- pecially carcinogenesis process. This phenomenon can lead to a chromosomal instability, contributing to a cell immortalization and tumor induction. In our study, we analyzed the role of telomere shortening in cancer progression, in Tunisian patients with digestive cancer. We measured the absolute telomere length in tumoralvshealthy adjacent tissues of each patient by using a q-RT PCR method and we investigated the relationship between telomere length and various sociodemographic and clinical parameters such as age, sex, tumor stage. In this pathological situation, we observed that, starting from 60 years of age, the telomere length increases in healthy mucosa and that in both healthy and cancer tissues, patients un- der 60 years have shorter telomeres, suggesting the telomere lengthening becomes more active with age. Finally, a positive correlation between normal and cancer tissues in both non-metastatic and metastatic stages, indicates telomere length in cancer tissue depends essentially on tumor stages. Our data allow us to suggest that telomere length depends on sex and age in healthy tissue while shortening and length- ening fluctuates considerably according to the tumor stage.

Background Late Life Bipolar Disorder (LLBD) is associated with a high prevalence of cognitive impairments, but few studies have examined their risk factors and clinical correlates Methods Participants with bipolar disorder older than 60 ( n = 86) were recruited from psychiatric outpatient and inpatients units. Patients were assessed with various instruments, including the Clinical Dementia Rating scale, the Montreal Cognitive Assessment and the Cumulative Illness Rating Scale. The distribution of disorder-specific and general risk factors was compared between patients with LLBD plus cognitive impairments (mild cognitive impairment or dementia) and those with LLBD but no cognitive impairment. Analyses were first conducted at the bivariate level, then using multiple regression. The association with disability, aggressive behavior and suicidal ideation was also explored. Results Cognitive impairments in LLBD were associated with a diagnosis of type 1 bipolar disorder (OR = 6.40, 95%CI: 1.84 – 22.31, p = 0.004), fewer years of education (OR = 0.79, 95%CI: 0.69 – 0.91, p = 0.001) and higher severity of physical diseases (OR 26.54, 95%CI: 2.07 – 340.37, p = 0.01). Moreover, cognitive impairments were associated with an increased likelihood of disability and recent aggressive behavior, but not suicidal ideation. Limitations retrospective design, conflation of MCI and dementia, not all subjects were in euthymia Conclusions In LLBD, the presence of cognitive impairments was associated with a diagnosis of type I bipolar disorder, lower education and more severe physical comorbidities. In turn, MCI or dementia were associated with increased disability and aggressive behavior. These findings may aid the identification of patients at risk for cognitive deterioration in everyday clinical practice.

The aim of the study is to analyze and report the results of the surgical activity in a spinal unit of a trauma hub in central Italy during COVID-19 pandemic. Surgical activity was compared between COVID 19 pandemic and the same period of time in 2019 at our institution. A 50% reduction of surgical procedures during the last three months was observed compared with the same period of time in 2019. The compliance with the containment rules for the spread of the infection, were sufficient to allow safe surgical activity for the medical teams and patients.

The study aimed to compare effectiveness and safety of short-term antidepressant treatment between patients with continuous (CCC) and non-continuous (N-CCC) cycling bipolar disorders.The study sample included 101 patients with bipolar disorder, 22 (21.8%) CCC and 79 (78.2%) N-CCC. Response was defined as a HDRS21 total score7 at 12 weeks of treatment and remission as a ≥50% reduction of baseline HDRS21 total score sustained for 8 weeks.Compared with N-CCC patients, CCC patients achieved a significantly lower percentage of response (respectively 50% vs. 82.3%, χ²=9.6, p=0.002) and remission (respectively 40.9% vs. 69.6%, χ²=6.11, p=0.013). Adjusted logistic regression analysis indicated that CCC patients were 4.3 times more likely to be non-responders and 3.3 times more likely to be non-remitters than N-CCC patients.AD safety, 1 (5.0%) CCC patient committed a suicide attempt and AD-emerging switch was observed in 2 patients with N-CCC (2.5%) and in 1 with CCC (4.5%).The observational nature of the study, retrospective assessment of course, and unblinded outcomes assessment.Our findings indicate that the presence or absence of a free interval identifies two different forms of bipolar disorders with different response not only to prophylactic treatment, as previously reported, but also to short-term ADs. We submit that clinicians should take into consideration their patients׳ pattern of cycling when prescribing short-term AD treatment. Moreover, subtypes of bipolar disorders might be used as moderators of treatment response in studies assessing the efficacy or the effectiveness of antidepressant treatment.

The study aimed to test the effectiveness of the ISBD Guidelines for short-term AD treatment of BP depression.The study sample included 255 patients with mood disorders (154 UP, 49 BP-I, 52 BP-II). Response was defined as a HDRS21 total score7 at 12 weeks of treatment and remission as a ≥50% reduction of baseline HDRS21 total score sustained for 8 weeks.Response was achieved by 64.9% of patients with UP disorder, 75.5% of patients with BP-I disorder and 75.0% with BP-II disorder without significant differences (χ²=3.0, p=0.219). The remission rate did not differ significantly among groups (χ²=3.8, p=0.151). The dropout rate was significantly higher for patients with UP (18.2%) than for patients with BP-I (2%) and BP-II (7.7%) disorder (χ²=10.1, p=0.006). Concerning AD safety, one patient with BP-I depression committed a suicide attempt and AD-emerging switch was observed in 2.9% of patients, 2 with BP-I and 1 with BP-II disorder.The observational nature of the study and unblinded outcomes assessment.Our findings confirm the usefulness of ISBD Guidelines for short-term AD treatment of BP depression. These patients appear to have similar response and remission rate to those observed in UP depression and do not exhibit significant switch rates or risk of suicide. Our results are limited to patients with pure bipolar depression (excluding those with broadly defined mixed states), treated with ADs-mood stabilizers combination. We suggest to partially modify ISBD Recommendations 1 and 4, to include potential responders and to improve safety.

Objective This prospective study aims to determine if patients with bipolar disorder with a continuous circular course (CCC) are significantly different on clinical characteristics and response to long-term treatment from those with a non-continuous circular course (N-CCC). CCC was defined as the alternation of depression and (hypo)mania without a completely free interval, and N-CCC as the presence of free intervals after the sequence mania–depression or depression–mania. Method The study sample includes 140 consecutive patients with bipolar I or II disorder according to DSM-IV criteria, aged 18–65 years and receiving prophylactic treatment for. Treatment was based upon international guidelines and clinical experience at the time of patient's enrollment (from January 1998 to January 2006). Primary outcome was the absence of new episodes during the follow-up. Significance level was set at p Results Twenty-eight percent of the sample has CCC. Compared with N-CCC, CCC patients were older, had a later onset, a higher number of total, depressive and (hypo)manic episodes, and of switches, and spent a higher percentage of time ill in the year before entering the study. Polarity at onset and subsequent recurrences were more frequently mixed in N-CCC than in CCC patients. The proportion of patients in the CCC group who had no recurrences during the follow-up was significantly lower than in the N-CCC group. Conclusion The presence or absence of a free intervals over the course of illness identifies two subtypes of bipolar disorder that differ in clinical presentation, outcome, and response to long-term treatment.

Highlights ► CSB protein is overexpressed in cancer cells and tissues. ► Suppression of CSB in cancer cells resulted in cell proliferation arrest and marked increase in apoptosis. ► Down-regulation of CSB made cancer cells hypersensitive to anti-cancer chemotherapeutic drugs., In the present study we show that a number of cancer cell lines from different tissues display dramatically increased expression of the Cockayne Syndrome group B (CSB) protein, a DNA repair factor, that has recently been shown to be involved in cell robustness. Furthermore, we demonstrated that ablation of this protein by antisense technology causes devastating effects on tumor cells through a drastic reduction of cell proliferation and massive induction of apoptosis, while non-transformed cells remain unaffected. Finally, suppression of CSB in cancer cells makes these cells hypersensitive to a variety of commonly used cancer chemotherapeutic agents. Based on these results, we conclude that cancer cells overexpress CSB protein in order to enhance their anti-apoptotic capacity. The fact that CSB suppression specifically affects only cancerous cells, without harming healthy cells, suggests that CSB may be a very attractive target for the development of new anticancer therapies.

The epidermis has evolved to provide a barrier against the environment, which is essential for survival. This barrier is constituted and continuously regenerated by terminally differentiating keratinocytes. Here, we summarize the main features of the response to UVB and oxidizing agents of human keratinocytes and compare it with that of fibroblasts. Keratinocytes are more resistant to the lethal effects of UVB than fibroblasts and remove cyclobutane pyrimidine dimers (CPD) more efficiently than fibroblasts. UV photoproducts are repaired by the nucleotide excision repair (NER) system by two distinct sub-pathways: global genome repair (GGR) that repairs lesions on the genome overall, and transcription coupled repair (TCR) that operates on transcribed sequences of active genes. By using NER-defective cells we demonstrated that the improved repair of UVB damage by keratinocytes is due to a more efficient GGR. A defect in TCR was associated with a strong apoptotic response in fibroblasts but not in keratinocytes, whereas a defect in GGR had no effect on the apoptotic response of either cell type. We speculate that the persistence of CPD in the transcribed sequences triggers apoptosis in fibroblasts but not in keratinocytes where GGR operates as back-up system to remove transcription-blocking lesions. As observed for UVB, keratinocytes are also more resistant to the lethal effects of oxidizing agents than fibroblasts. We show that keratinocytes are characterized by a strong anti-oxidant capacity and a higher susceptibility to reactive oxygen species (ROS)-induced apoptosis than fibroblasts. All together these results provide a clear evidence that the response to environmental agents is strongly affected by the type of damage as well as by the cellular background.

International audience; The Rift Valley fever virus (RVFV) is the causative agent of fatal hemorrhagic fever in humans and acute hepatitis in ruminants. We found that infection by RVFV leads to a rapid and drastic suppression of host cellular RNA synthesis that parallels a decrease of the TFIIH transcription factor cellular concentration. Using yeast two hybrid system, recombinant technology, and confocal microscopy, we further demonstrated that the nonstructural viral NSs protein interacts with the p44 component of TFIIH to form nuclear filamentous structures that also contain XPB subunit of TFIIH. By competing with XPD, the natural partner of p44 within TFIIH, and sequestering p44 and XPB subunits, NSs prevents the assembly of TFIIH subunits, thus destabilizing the normal host cell life. These observations shed light on the mechanism utilized by RVFV to evade the host response.

International audience; Mutations in the XPD gene result in xeroderma pigmentosum (XP) and trichothiodystrophy (TTD), the phenotypes of which are often intricate. To understand the genotype/phenotype relationship, we engineered recombinant TFIIHs in which XPD subunits carry amino acid changes found in XPD patients. We demonstrate that all the XPD mutations are detrimental for XPD helicase activity, thus explaining the NER defect. We also show that TFIIH from TTD patients, but not from XP patients, exhibits a significant in vitro basal transcription defect in addition to a reduced intracellular concentration. Moreover, when XPD mutations prevent interaction with the p44 subunit of TFIIH, transactivation directed by certain nuclear receptors is inhibited, regardless of TTD versus XP phenotype, thus explaining the overlapping symptoms. The implications of these mutations are discussed using a structural model of the XPD protein. Our study provides explanations for the nature and the severity of the various clinical features.

Transcription coupled repair (TCR), a special sub-pathway of nucleotide excision repair (NER), removes transcription blocking lesions rapidly from the transcribing strand of active genes. In this study, we have evaluated the importance of the TCR pathway in the induction of chromosomal aberrations and apoptosis in isogenic Chinese hamster cell lines, which differ in TCR efficiency. AA8 is the parental cell line, which is proficient in the genome overall repair of UV-C radiation induced 6-4 photoproducts (6-4 PP) and the repair of cyclobutane pyrimidine dimer (CPD) from the transcribing strand of active genes. UV61 cells (hamster homologue of human Cockayne’s syndrome (CS) group B cells) originally isolated from AA8, exhibit proficient repair of 6-4 PP but are deficient in CPD removal by the TCR pathway. Upon UV-C irradiation of cells in G1-phase, UV61 showed a dramatic increase in apoptotic response as compared to AA8 cells. Abolition of TCR by treatment with α-amanitin (an inhibitor of RNA polymerase II) in AA8 cells also resulted in an elevated apoptotic response like that observed in UV61 cells treated with UV alone. This suggests that the lack of TCR is largely responsible for increased apoptotic response in UV61 cells. Furthermore, the chromosomal aberrations and sister chromatid exchange (SCE) induced by UV were also found to be higher in UV61 cells than in TCR proficient AA8 cells. This study shows that the increased chromosomal aberrations and apoptotic death in UV61 cells is due to their inability to remove CPD from the transcribing strand of active genes and suggests a protective role for TCR in the prevention of both chromosomal aberrations and apoptosis induced by DNA damage. Furthermore, flow cytometry analysis and time-course appearance of apoptotic cells suggest that the conversion of UV-DNA damage into chromosomal aberrations precedes and determines the apoptotic process.

Italian Abstract: Il presente documento e stato concepito nel quadro del lavoro svolto dal Team di Progetto n. 6 del Workshop Dirigenti “Obiettivo Global Player”, come una breve e agile raccolta organica di termini e concetti utili alla migliore comprensione del supply chain management, inteso come gestione, in chiave strategica ed integrata, dei rapporti con i fornitori e, piu in generale, con tutti i collaboratori con i quali si intrattengono rapporti per realizzare la produzione. Il glossario e stato elaborato con un linguaggio estremamente semplice e, al contempo, sintetico, avendo come obiettivo soprattutto la chiarezza e la sistematicita. I termini considerati sono stati selezionati in modo tale da abbracciare anche tematiche “di frontiera” rispetto al supply chain management in senso stretto. Cio in considerazione del fatto che, nella concreta realta delle organizzazioni imprenditoriali complesse, la gestione moderna e attenta alla logistica e ai rapporti con fornitori e partner, supera la dimensione strettamente specialistica della singola funzione aziendale, per investire aspetti trasversali all’ impresa e al suo rapporto con l’ambiente, come il modello di business complessivo, l’assetto organizzativo interno, i legami con i territori, ecc. English Abstract: Project Team n. 6 of the Executive Workshop “Objective Global Player”, as a quick and agile complete collection of terms and concepts useful for better understanding of supply chain management, understood as management, in a strategic and integrated relationships with suppliers and, more generally , with all the partners with whom they have relationships to achieve the production. The glossary was developed extremely simple and at the same time, synthetic, targeting especially the clear and systematic way. The terms considered were selected so as to embrace matters “border” with respect to supply chain management in the strict sense. This is due to the fact that, in the concrete reality of complex business organizations, modern management and careful logistics and relationships with suppliers and partners, than the purely specialist of single business function, to invest the company and its cross-cutting issues relationship with the environment, as the overall business model, the internal organizational structure, links with the territories, etc.

Background Aim of the study was to evaluate degenerative lumbar facet joint changes after percutaneous pedicle screw fixation (PPSF) in the treatment of lumbar fractures. Patients and methods Thirty patients underwent short PPSF without fusion. CT scan was performed in the pre- and postoperative time at 4, 8 and 12 months. The 6 zygapophyseal joints adjacent the fracture's level were evaluated. Results At 4 months patients showed no differences between pre- and postoperative joint radiographic aspect. At 8 and 12 months CT scan demonstrated a progressive degeneration only in the middle joints respectively in 21.42% and in 76.92% of the cases. All 10 disrupted facet joints showed progressive degenerative changes at 8 and 12 months. Conclusion Lumbar percutaneous fixation without fusion induces little degenerations essentially collocated in the middle joints close to fracture level at 8 and 12 months. In the proximal and distal joints adjacent the screws degenerative changes can be seen only when associated to pedicle screw encroachment. Level of evidence Level IV, retrospective study.

Background Treatment of A3 thoracolumbar and lumbar spinal fractures nowadays remains a controversial issue. Percutaneous techniques are becoming very popular in the last few years to reduce the approach-related morbidity associated with conventional techniques. Hypothesis Purpose of the study was to analyze the clinical and radiological outcome of patients who underwent percutaneous posterior fixation without fusion for the treatment of thoracolumbar and lumbar A3 fractures. Materials and methods Sixty-three patients, having sustained a single-level thoracolumbar fracture, underwent short segment percutaneous instrumentation and were retrospectively analyzed way. Sagittal Index (SI) was calculated in all patients. Clinical and functional outcome were evaluated by Visual Analog Scale (VAS), Oswestry Disability Index (ODI) and Short Form General Health Status (SF-36). Results Average operative blood loss was 82 mL (50–320). Mean pre-operative SI in the thoraco-lumbar segment was 13.3° decreased to 5.8° in the immediate post-operative with a mean deformity correction of 7.5. Mean pre-operative SI in the lumbar segment was 16.5° decreased to 11.3° in the immediate post-operative with a mean deformity correction of 5.2. Not statistically significant correction loss was registered at 1 year minimum follow-up. Constant clinical conditions improvement in the examined patients was observed. Conclusion Percutaneous pedicle screw fixation for A3 thoracolumbar and lumbar spinal fractures is a reliable and safe procedure. Level of evidence Level IV. Retrospective study.

Summary One case of cervical myelopathy associated to ossification of transverse atlantal ligament (OTAL) and C1 posterior arch hypoplasia in a Caucasian adult female is reported. A 53-years-old female affected by cervical myelopathy was treated with C1 laminectomy and posterior arthrodesis. CT scan demonstrated that the distance between ossification of the ligament and anterior cortex of the posterior arch of atlas was 6.2 mm leading to consistent space reduction for spinal cord at this level. Patient underwent spinal cord decompression and fixation with C1 poliaxial screws in lateral masses and two bilateral crossing C2 laminar screws with an improvement of neurological functions at 4 years follow-up. The association between OTAL and C1 hypoplasia was reported in very few cases. The treatment with C1 laminectomy without fusion is reported in medical literature with good clinical outcome. Our patient obtained a neurological improvement at midterm follow-up with spinal cord decompression and fusion.