Periodic Bedrock Ridges at the ExoMars 2022 Landing Site: Evidence for a Changing Wind Regime.

Wind-formed features are abundant in Oxia Planum (Mars), the landing site of the 2022 ExoMars mission, which shows geological evidence for a past wet environment. Studies of aeolian bedforms at the landing site were focused on assessing the risk for rover trafficability, however their potential in recording climatic fluctuations has not been explored. Here we show that the landing site experienced multiple climatic changes in the Amazonian, which are recorded by an intriguing set of ridges that we interpret as Periodic Bedrock Ridges (PBRs). Clues for a PBR origin result from ridge regularity, defect terminations, and the presence of preserved megaripples detaching from the PBRs. PBR orientation differs from superimposed transverse aeolian ridges pointing toward a major change in wind regime. Our results provide constrains on PBR formation mechanisms and offer indications on paleo winds that will be crucial for understanding the landing site geology.

Development of adaptive immune effector therapies in solid tumors.

State-of-the-art treatment strategies have drastically ameliorated the outcome of patients affected by cancer. However, resistant and recurrent solid tumors are generally nonresponsive to conventional therapies. A central factor in the sequence of events that lead to cancer is an alteration in antitumor immune surveillance, which results in failure to recognize and eliminate the transformed tumor cell. A greater understanding of the dysregulation and evasion of the immune system in the evolution and progression of cancer provides the basis for improved therapies. Targeted strategies, such as T-cell therapy, not only generally spare normal tissues, but also use alternative antineoplastic mechanisms that synergize with other therapeutics. Despite encouraging success in hematologic malignancies, adaptive cellular therapies for solid tumors face unique challenges because of the immunosuppressive tumor microenvironment, and the hurdle of T-cell trafficking within scarcely accessible tumor sites. This review provides a brief overview of current cellular therapeutic strategies for solid tumors, research carried out to increase efficacy and safety, and results from ongoing clinical trials.

Cord blood transplantation is associated with good outcomes in secondary Acute Myeloid Leukaemia in first remission.

BACKGROUND: We conducted a retrospective survey within the European Society for Blood and Marrow Transplantation (EBMT) registry to assess the outcomes of cord blood transplantation (CBT) in secondary acute myeloid leukaemia (sAML). METHODS: Inclusion criteria consisted of ≥18 years of age, sAML, first CBT between 2002 and 2016, and either first complete remission (CR) or active disease at CBT. RESULTS: One hundred forty-six patients met the study inclusion criteria. Status at transplantation was first CR (n = 97), primary refractory sAML (n = 30) or relapsed (n = 19) sAML. Neutrophil engraftment was achieved in 118 patients while the remaining 25 patients (17%) failed to engraft. This includes 13% of patients transplanted in first CR versus 30% of those transplanted with active disease (P = 0.008). Two-year incidences of relapse were 25% in first CR patients versus 36% in those with advanced disease (P = 0.06) while 2-year incidences of nonrelapse mortality were 35% and 49% (P = 0.03), respectively. At 2-year overall survival, leukaemia-free survival and graft-versus-host disease (GVHD)-free relapse-free survival were 42% vs. 19% (P < 0.001), 40% vs. 16% (P < 0.001), and 26% vs. 12% (P = 0.002) in first CR patients versus those with advanced disease, respectively. CONCLUSIONS: We report here the first study of CBT in a large cohort of sAML patients. Main observation was that CBT rescued approximately 40% of patients with sAML in first CR.

Hong-Ou-Mandel interference between independent III-V on silicon waveguide integrated lasers.

The versatility of silicon photonic integrated circuits has led to a widespread usage of this platform for quantum information-based applications, including quantum key distribution (QKD). However, the integration of simple high-repetition-rate photon sources is yet to be achieved. The use of weak-coherent pulses (WCPs) could represent a viable solution. For example, measurement device independent QKD (MDI-QKD) envisions the use of WCPs to distill a secret key immune to detector side channel attacks at large distances. Thus, the integration of III-V lasers on silicon waveguides is an interesting prospect for quantum photonics. Here we report the experimental observation of Hong-Ou-Mandel interference with 46±2% visibility between WCPs generated by two independent III-V on silicon waveguide integrated lasers. This quantum interference effect is at the heart of many applications, including MDI-QKD. This Letter represents a substantial first step towards an implementation of MDI-QKD fully integrated in silicon and could be beneficial for other applications such as standard QKD and novel quantum communication protocols.

Occurrence of graft-versus-host disease increases mortality after umbilical cord blood transplantation for acute myeloid leukaemia: a report from Eurocord and the ALWP of the EBMT.

BACKGROUND: The efficacy of umbilical cord blood transplantation (UCBT) as treatment for acute myeloid leukaemia (AML) relies on immune-mediated graft-versus-leukaemia effects. Previous studies have suggested a strong association between graft-versus-host disease (GVHD) occurrence and graft-versus-leukaemia effects after allogeneic hematopoietic cell transplantation. METHODS: Here, we evaluated the kinetics of relapse rate in correlation with GVHD occurrence after UCBT. The kinetics of relapse rate over time in correlation to GVHD occurrence were assessed by calculating the relapse rate per patient-year within sequential 90-day intervals. The impact of GVHD on relapse and mortality was further studied in multivariate Cox models handling GVHD as a time-dependent covariate. RESULTS: The study included data from 1068 patients given single (n = 567) or double (n = 501) UCBT. The proportion of patients with grade II, III and IV acute GVHD was 20%, 7% and 4%, respectively. At 2 years, the cumulative incidence of chronic GVHD was 42%, the cumulative incidence of relapse was 32%, and overall survival was 32% as well. Relapse rates declined gradually over time during the first 30 months after transplantation. There was a possible suggestion that grade II-IV acute (HR = 0.8, P = 0.1) and chronic (HR = 0.65, P = 0.1) GVHD decreased relapse risk. However, grade II-IV acute GVHD significantly increased early (the first 18 months after UCBT) mortality (HR = 1.3, P = 0.02), whilst chronic GVHD increased each early (HR = 2.7, P < 0.001) and late (HR = 4.9, P < 0.001) mortality after UCBT. CONCLUSIONS: The occurrence of grade II-IV acute or chronic GVHD each increases overall mortality after UCBT for AML mitigating the possible graft-versus-leukemia effect of GVHD.

Current practices for screening, consent and care of related donors in France: Haematopoietic stem cell transplantation coordinator nurses' perceptions.

Haematopoietic stem cell transplantation-coordinating nurses (HSCT-CNs) play an important role in informing related donors (RDs) and in organising human leucocyte antigen (HLA) tests, pre-donation workup and stem cells collection. Our pilot study aimed to explore French HSCT-CNs' perceptions of RD care issues. Twenty-nine French HSCT adult units were sent a questionnaire on the subject of donation procedures, HSCT-CNs' data and their professional experience of related donation issues. Twenty-two HSCT-CNs returned a completed questionnaire, and 90% of HSCT units were involved to some degree in both patient and donor care. Responses indicated that the provision of information to potential donors prior to HLA tests was insufficient, while donors were given a medical consultation only during the pre-donation workup. Questions were raised about the consent and voluntary status of RDs. None of the HSCT teams organised a post-donation consultation, while 57% provided follow-up by phone or via a questionnaire. Our results draw attention to the conflict of interest experienced by HSCT-CNs when caring simultaneously for patients and donors. The specific psychosocial difficulties associated with becoming an RD are also highlighted. French HSCT-CNs' perceptions of related donation reveal many ethical and clinical problems that have yet to be fully explored. Data on this topic remain scarce, and our pilot study may contribute to the current debate on the organisation of RD care.

Randomized noninferiority field trial comparing 2 first-generation cephalosporin products at dry off in quarters receiving an internal teat sealant in dairy cows.

The study objective was to compare 2 commercial dry cow mastitis products at the quarter level, with concurrent internal teat sealant application, evaluating the cure risk difference, odds of a cure, odds of a new intramammary infection (NIMI) during the dry period, and risk for a clinical mastitis (CM) case between calving and 60d in milk (DIM). A total of 590 cows (2,360 quarters) from 8 commercial dairy herds in Italy were enrolled and randomized to 1 of the 2 treatments at dry off: Cefovet A (CF; 250mg of cephazoline; Merial Italia SpA, Milan, Italy), and Cepravin (CP; 250mg of cephalonium dehydrate MSD Animal Health Srl, Segrate, Italy). Quarter milk samples were collected before dry cow therapy treatment at dry off, 2 to 9 DIM, and 10 to 17 DIM. Quarter milk samples from CM cases were collected during the first 60 DIM. Noninferiority analysis was used to evaluate the effect of treatment on the risk difference of a bacteriological cure during the dry period, the primary outcome. The odds of cure, developing a NIMI during the dry period, and the risk of a CM event within 60 DIM were evaluated with multivariable logistic regression and hazard analysis, respectively. The overall crude quarter-level prevalence of NIMI at dry off was 15.3%. The most common pathogen isolated from milk samples at dry-off was coagulase-negative staphylococci. Noninferiority analysis showed no effect of treatment on the risk difference for a cure between dry off and both postpartum samples, difference was 0.013. The least squares means from the multivariable model evaluating the odds of cure was 94% for CF and 95%for CP. We observed no effect of treatment on the odds for the presence of a NIMI at 2 to 9 DIM (least squares means: CF=0.09 and CP=0.07), nor did we note a difference in risk of experiencing a CM event between calving and 60 DIM (hazard ratio=0.8). In conclusion, no difference was observed between the 2 products evaluated when assessing the aforementioned outcomes in quarters also receiving an internal teat sealant.

Microbiological Quality of the Water used in Agriculture in Sardinia.

BACKGROUND: The microbiological quality of the water used in irrigation is crucial for the safety of products, such as fruit and vegetables, especially when destined to be consumed raw. However, the microbiological quality of this water is not defined at a community regulatory level or at a national level. METHODS: With our present work, we wanted to investigate the microbiological quality of the water used for crop irrigation in various Sardinian provinces. Since in most fields the irrigation water is filtered to remove any impurities, the sample was processed twice - both before and after the filtering process. Furthermore, with the purpose of hypothesising the potential health risks attributable to the consumption of crops from the tested fields, samples of horticultural product were collect. Any eventual seasonal differences in the values of microbial concentration were assessed. Microorganism faecal contamination indicators (Escherichia coli, total coliform and faecal streptococci), but even the presence of the opportunistic pathogen such as Pseudomonas aeruginosa were researched in irrigation water. Total mesophilic counts (TMC) were assessed at 36°C and 22°C. On horticultural products we researched both the indicators of process parameters, such as Escherichia coli, Total mesophilic counts at 30°C, Enterobacteriaceae, Total Psychrophilic counts and Pseudomonas aeruginosa, and pathogens, such as Salmonella spp, Listeria monocytogenes and Yersinia enterocolitica. RESULTS: The number of target microorganisms, when present in irrigation water, was very limited: Escherichia coli, total coliform and faecal streptococci, were detected respectively in 48% and 67% of the water samples tested with average concentration values of 0.9, 1.2 and 1.4 log respectively. In fresh vegetable products, the total mesophilic counts (TMC) were found to have average values of 6.6x107 CFU/g. The average values of Enterobacteriaceae totalled 6.1x105 CFU/g; Escherichia coli was detected in only one sample (curly endive) with a value of 180 CFU/g. CONCLUSION: The data highlights the high quality of the water and how this contributed to achieving satisfactory quality on prime material. However the use of filters, to eliminate impurities, and reservoirs, may represent a crucial issue, if not managed correctly.

Incidence and risk factors for hemorrhagic cystitis in unmanipulated haploidentical transplant recipients.

BACKGROUND: Hemorrhagic cystitis (HC) is a common complication after hematopoietic allogeneic stem cell transplantation (HSCT) associated with intensity of the conditioning regimen, cyclophosphamide (Cy) therapy, and BK polyomavirus (BKPyV) infection. METHODS: We analyzed 33 consecutive haploidentical (haplo) HSCT recipients transplanted for hematologic diseases. Eleven patients had a previous transplant. Median follow-up was 11 months. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine + mycophenolate mofetil and post-HSCT Cy. RESULTS: Thirty-two of 33 patients achieved neutrophil recovery. Cumulative incidence (CI) of platelet recovery was 65%. CI grade II-IV acute GVHD was 44%. Twenty patients developed HC in a median time of 38 days. CI of HC at day 180 was 62%. BKPyV was positive in blood and urine of 91% of patients at HC onset. HC resolved in 18/20 patients. Factors associated with HC were previous transplant (P = 0.01) and occurrence of cytomegalovirus reactivation before HC (P = 0.05). Grade II-IV acute GVHD was not associated with HC (P = 0.62). CI of day 180 viral infections was 73%. Two-year overall survival (OS) was 50%; HC did not impact OS (P = 0.29). CONCLUSION: The incidence of HC after haplo with post-HSCT Cy is high and is associated with morbidity, especially in high-risk patients such as those with a previous transplant history and with impaired immune reconstitution.

Fresh or frozen grafts for allogeneic stem cell transplantation: conceptual considerations and a survey on the practice during the COVID-19 pandemic from the EBMT Infectious Diseases Working Party (IDWP) and Cellular Therapy & Immunobiology Working Party (CTIWP).

The COVID-19 pandemic has had a significant impact on medical practices, including the delivery of allogeneic hematopoietic cell transplantation (HCT). In response, transplant centers have made changes to their procedures, including an increased use of cryopreservation for allogeneic haematopoietic progenitor cell (HPC) grafts. The use of cryopreserved grafts for allogeneic HCT has been reviewed and analysed in terms of potential benefits and drawbacks based on existing data on impact on cell subsets, hematological recovery, and clinical outcomes of approximately 2000 patients from different studies. A survey of European Society for Blood and Marrow Transplantation centers was also conducted to assess changes in practice during the pandemic and any unnecessary burdens on HPC donors. Before the pandemic, only 7.4% of transplant centers were routinely cryopreserving HPC products, but this percentage increased to 90% during the pandemic. The results of this review and survey suggest that cryopreservation of HPC grafts is a viable option for allogeneic HCT in certain situations, but further research is needed to determine long-term effects and ethical discussions are required to balance the needs of donors and patients when using frozen allografts.

Clinical applicability of Quantiferon-TB-Gold testing in psoriasis patients during long-term anti-TNF-alpha treatment: a prospective, observational study.

BACKGROUND: Psoriasis patients who are treated with tumour necrosis factor (TNF)-alpha antagonists are at increased risk of reactivation of latent tuberculosis infection (LTBI) and should be adequately screened and monitored during active treatment. OBJECTIVES: To evaluate in a prospective study, the performance of Quantiferon-TB-Gold in tube (QFT) in vitro assay compared to the conventional tuberculin skin test (TST) in detecting LTBI among a cohort of non-BCG-vaccinated patients with moderate-to-severe psoriasis during long-term treatment (12 months) with TNF-alpha antagonists. METHODS: A total of 50 patients underwent QFT and TST testing at baseline and after 6 and 12 months of continuous anti-TNF-alpha treatment. Diagnosis of LTBI was made on the basis of a positive QFT result and negative chest-radiographic and microbiological assays. Patients with LTBI were subjected to standard isoniazid chemoprophylaxis and after 1 month, they resumed anti-TNF-alpha treatment with subsequent QFT and TST testing after 6 months. In all the cases, a follow-up period of 12 months was observed. RESULTS: During the 12-month-study period, 14% of patients presented a QFT conversion. During active anti-TNF-alpha treatment, a QFT conversion was observed in 10% of patients (five cases). Agreement between QFT and TST was moderate (κ=0.408) at screening, good (κ=0.734) after 6 months and fair (κ=0.328) after 12 months of treatment. A total of 18% of patients presented a positive, discordant TST during the study period. CONCLUSIONS: A single-test QFT-based screening strategy for LTBI in psoriasis patients receiving long-term anti-TNF-alpha treatment could reduce the incidence of false-positive LTBI cases, preventing unnecessary TB chemoprophylaxis.

Microsurgical excision without fusion as a safe option for resection of synovial cyst of the lumbar spine: long-term follow-up in mono-institutional experience.

Spinal synovial cysts are cystic dilatations of the synovial membrane that may arise at all levels of the spine. We describe our experience, paying attention to diagnosis, surgical treatment, and long-term follow-up. Between 1995 and 2007, 18 patients were surgically treated. Of these, three patients were excluded from the study because they presented spinal instability at pre-operative assessment. All patients were evaluated pre-operatively with CT, MRI, and dynamic X-rays, and underwent surgery for removal of the cyst by hemilaminectomy and partial arthrectomy. All patients were evaluated with early MRI and had a minimum 2-year follow-up by dynamic X-rays. None of the patients required instrumented fusion due to the absence of radiological signs of instability on the pre-operative dynamic tests. In all patients, there was an immediate resolution of the symptoms, with evidence of complete removal of the cysts on post-operative MRI. At 2-year follow-up, all patients underwent dynamic X-rays and responded to a questionnaire for evaluation of outcome. None of them showed signs of relapse. The gold standard for treatment is surgery, even though other conservative treatment regimens have been proposed. Correct surgical strategy relies on pre-operative assessment of biomechanical stability for deciding whether patients need instrumented fusion during cyst removal. Patients with no instability signs are suitable for hemilaminectomy with partial arthrectomy, preserving 2/3 of the medial portion of the articular facet, because this represents a valid option of treatment with a low risk of complications and a low rate of relapse.

Outcomes, infections, and immune reconstitution after double cord blood transplantation in patients with high-risk hematological diseases.

Double unrelated cord blood transplant (dUCBT) has been used to circumvent cell dose limitation of single UCBT; however, few data are available describing outcomes, infectious disease, and immune recovery. We analyzed 35 consecutive dUCBT recipients with high-risk malignant disorders (n=21) and bone marrow failure syndromes (n=14). Median follow-up was 32 months. Conditioning regimen was myeloablative in 14 and reduced intensity in 21 patients. Median infused nucleated cell dose was 4 × 10(7) /kg. Median time to absolute neutrophil count >0.5 × 10(9) /L was 25 days. Cumulative incidence (CI) of acute grade II-IV graft-versus-host disease was 47%. Estimated overall survival at 2 years was 48%. CI of first viral infections at 1 year was 92%. We observed 49 viral infections in 30 patients, 34 bacterial infections in 19 patients, and 16 fungal or parasitic infections in 12 patients. Lymphocyte subset analyses were performed at 3, 6, 9, and >12 months after dUCBT. Decreased T-cell and B-cell counts with expansion of natural killer cells were observed until 9 months post transplantation. Recovery of thymopoiesis measured by T-cell receptor excision circles was impaired until 9 months after dUCBT, when the appearance of new thymic precursors was observed. Delayed immune recovery and high incidence of infectious complications were observed after dUCBT in patients with high-risk hematological diseases.

Five-year outcome of stand-alone fusion using carbon cages in cervical disc arthrosis.

From January 1, 2001 to December 31, 2003, in the Neurosurgery Department of Rome University o "Sapienza," 167 patients underwent anterior surgery for cervical spondylodiscoarthrosis. The levels treated by the anterior stand-alone technique were: C3-C4 (11%), C4-C5 (19%), C5-C6 (40%), and C6-C7 (30%). All patients underwent left anterior presternocleidomastoid-precarotid approach, microdiscectomy, and interbody fusion using a carbon fiber cage filled with hydroxyapatite. All patients were discharged within 48 h after surgery with cervical orthosis. In one case, a hematoma of the surgical site occurred within 12 h of surgery; for this reason the patient underwent surgical revision and was discharged 4 days later. All patients have worn cervical orthosis for a mean period of 7 weeks and underwent radiological follow-up with cervical RX at 1 and 3 months after surgery. All patients underwent follow-up from 54 to 90 months after surgery, and all of them underwent cervical RX, cervical CT scans for the estimate of fusion, and evaluation of neurological status using VAS and NDI. Of 167 patients, 132 were cooperative for this study, 18 were non-cooperative, and 17 died. The estimation of fusion made by cervical CT scans with sagittal reconstruction showed complete osteointegration of the cage in 115 patients (87.1%), while it showed pseudoarthrosis in 17 patients (12.9%). In 24 patients, we observed adjacent segment degeneration, and 13 of these underwent new surgical procedures in this institute or in another hospital. Clinical evaluation with VAS and NDI showed a good outcome, with poorest benefit in patients over 60 years. The clinical analysis showed a good fusion rate in according with literature, 13% of non-fusion rate without clinical evidence and 20% of ASDegeneration but only 10% had required new surgery. We also observed that patients over 60 years of age had less satisfactory outcome, probably related with the evolution of pathophysiological degeneration of the cervical spine. In the opinion, pseudoarthrosis is caused by malpositioning of the carbon fiber cage.

The use of platelet gel in postero-lateral fusion: preliminary results in a series of 14 cases.

Over the last few years, some hemocomponents have been used advantageously in clinical neurosurgical practice, not systemically via transfusion but topically as a sealant (fibrin glue). This has diverted the attention of many authors to the role of platelets in the healing process. The combination of hyper-concentrated platelets and fibrin glue (fibrinogen, XIII factor, fibronectin) with activated thrombin produces a platelet gel that can be easily applied to "difficult" wounds. This topical use of hemocomponents has gained an important role in regenerative medicine. The authors have considered the possibility of using a preparation with a high autologous platelet concentration applied in addition to autologous bone during vertebral postero-lateral fusion. The aim of the procedure is to induce a higher rate of vertebral fusion. Between November 2007 and November 2008, 14 patients (9 men and 5 women, mean age 58.9) underwent laminectomy, vertebral stabilization and postero-lateral fusion. The number of vertebral levels involved in stabilization was: 1 in 2 patients, 2 in 5 patients, 3 in 5 patients, 4 in 1 patient and 5 in 1 patient. Platelet gel was obtained by taking 16 ml of peripheral venous blood from the patient. For this procedure two patented test tubes were used for each patient, with a capacity of 8 m each. These make up the REGEN-THT(®) (Thrombocyte Harvesting Tube) system that makes it possible to obtain 8 ml of autologous platelet gel in 40-45 min. The addition of Ca gluconate and ethanol at 95% makes it possible to obtain a preparation of plasma rich in platelets and activated thrombin with a platelet concentration five times superior to the haematic one. The platelet gel is combined with fragments of autologous bone and synthetic bone during surgical operation. To allow a comparative assessment of the degree of fusion achieved with and without application of the platelet preparation in each patient, it was arbitrarily decided to use it in only one half of the operative field. All patients underwent serial CT scans 3 and 6 months after surgery as well as plain X-rays to evaluate bone fusion. The reconstructed CT images, especially in sagittal and axial planes, permitted an evaluation of the degree of vertebral fusion and "bone growth". The fusion rate was calculated measuring the increment of bone density on CT images, by means of an evaluation of the ROI (HU) in the newly formed bone, and comparing bone density within the bone callus formed by autologous and synthetic bone alone in the one to which the platelet preparation had been added. A good rate of fusion was observed in all patients. Furthermore, a comparative analysis of ROI at 3 and 6 months after surgery demonstrated a high increase in the fusion rate during the first 3 months after surgery. After 6 months the differences in ROI between the two sides had balanced out. However, at 6-month follow-up examination, bone density in the half of the surgical field in which platelet gel had been added to autologous-heterologous bone was higher in comparison to the contralateral one. Bony neoformation after posterior-lateral arthrodesis is well-evident 3 months after surgery and usually continues gradually for the following 18-24 months. The autologous platelet preparation used seems to accelerate bony deposition and to promote tissue healing, increasing bone density at the level of posterior-lateral arthrodesis. Moreover, this preparation has low production costs and is easy to apply.

Immunohistochemical and biochemical assay of versican in human sound predentine/dentine matrix.

Aim of this study was to investigate the distribution of versican proteoglycan within the human dentine organic matrix by means of a correlative immunohistochemical analysis with field emission in-lens scanning electron microscope (FEI-SEM), transmission electron microscope (TEM), fluorescence microscope (FM) and biochemical assay. Specimens containing dentine and predentine were obtained from non carious human teeth and divided in three groups: 1) FEI-SEM group: sections were exposed to a pre-embedding immunohistochemical procedure; 2) TEM group: specimens were fixed, demineralised, embedded and submitted to a post-embedding immunohistochemical procedure; 3) FM group: sections mineralised and submitted to a pre-embedding immunohistochemical procedure with fluorescence labelling. Specimens were exposed to two different antibodies to assay distribution of versican fragments and whole versican molecule.Western Blotting analysis of dentine and pulp extracts was also performed. The correlative FEI-SEM,TEM and FM analysis revealed positive immunoreaction for versican fragments both in predentine and dentine, while few gold particles identifying the whole versican molecule were found in predentine only under TEM. No labelling of versican whole molecule was detected by FEI-SEM and FM analysis. The immunoblotting analysis confirmed the morphological findings. This study suggests that in fully developed human teeth versican fragments are significant constituents of the human dentine and predentine organic matrix, while versican whole molecule can be visualised in scarce amount within predentine only. The role of versican fragments within human dentine organic matrix should be further elucidated.

Histomorphometric evaluation of implant design as a key factor in peri-implant bone response: a preliminary study in a dog model.

AIM: Primary implant stability as the establishment of a direct bone-to-implant contact (BIC) plays a major role in long-term successful implant osseointegration. Numerous factors influencing this initial stability have been studied. This preliminary in vivo study on a dog lower jaw aimed to investigate the hypothesis that primary implant stability in low density bone may be influenced by implant design. METHODS: The authors compared two different implant designs with regard to their immediate quantitative relation to host bone (BIC% and gap area, GA%). The screw-shaped implants, manufactured by Or-Vit (Castelmaggiore-Bologna, Italy), exhibited similar microroughness surface and two different thread pitches: ''narrow-pitch'' implants (NP) and ''wide-pitch'' implants (WP) with a 0.5 mm and 1.5 mm thread pitch respectively. Implants were placed in dog jaw after complete osseous healing of the extractive sockets, according to a delayed implantation procedure. Five hours after surgery the animal was sacrificed. Radiographic, histological, morphometric and ultrastructural analysis were performed. RESULTS: An inverse relation existed among the two parameters BIC and GA: GA, as a region with high osteogenetic potentiality, appeared wider in WP implants; BIC, as the expression of primary mechanical stability, was higher in NP implants. CONCLUSION: Based on this results, we could assume that NP implants might be the clinical choice in case of immediate loading.This single case study might be considered a starting point for further long term in vivo investigations aiming to establish the implant design that best favours osseointegration at different bone quality sites.

"Klingon headache" - a case report of mimic new daily persistent headache associated to primary essential cutis verticis gyrata.

BACKGROUND: Primary essential cutis verticis gyrata is a condition that usually affects healthy subjects associated to convoluted folds and furrows formed from thickened skin of the scalp resembling cerebriform pattern. CASE: we describe a case of association between primary essential cutis verticis gyrata and new daily persistent headache. DISCUSSION/CONCLUSIONS: In our knowledge this is the first description of new daily persistent headache associated with primary essential cutis verticis gyrata. We think that primary essential cutis verticis gyrata could be considered as a possible trigger factor, never described before, for the development of new daily persistent headache.

Determining the time of death by morphological and immunohistochemical evaluation of collagen fibers in postmortem gingival tissues.

The estimation of the post mortem interval (PMI) is still one of the most challenging variables to determine and the different approaches currently used in its estimation generally yield to large post mortem windows. In the present study we combined morphological and immunohistochemical analysis in order to reach a more detailed knowledge on tissue organization and degradation after death. Ultrastructural cellular changes and the extracellular matrix of gingival tissues, collected at different post mortem intervals, were observed by a Transmission Electron Microscopy (TEM), in combination with the immunohistochemical detection of extracellular matrix proteins (i.e. collagen type I and collagen type III) as potential post mortem biochemical markers. The final goal was to find a correlation between morphological modifications, biomarkers expression and the time of death. Samples of gingival tissues obtained from 10 cadavers at different post mortem intervals (short post mortem interval, 1-3 days; mid post mortem interval, 4-6 days; long post mortem interval, 7-9 days) were processed for light microscopy and TEM and they were also immunostained with anti-collagen type I and type III antibodies. Results showed gradual degradation of extracellular matrix in the suboral connective tissue in relation to the different time of death. Moreover PMI was related to an increase of nuclear chromatin condensation and cytoplasmic vacuolization both in epithelial and connective tissues. In conclusion, in addition to traditional forensic approaches to estimate PMI, the combined analyses of cellular morphology, ultrastructure and immunohistochemical expression of collagen proteins allow to better infer the PMI.