The role of bone anabolic drugs in the management of periodontitis: a scoping review.

The aim of this scoping review was to summarise current knowledge about the effects of bone anabolic drugs on periodontitis, in order to identify new therapeutic strategies for preventing disease progression and reducing tooth loss. A technical expert panel (TEP) was established of 11 medical specialists, including periodontists and bone specialists that followed the PRISMA-ScR model to perform the scoping review and considered for eligibility both pre-clinical and clinical studies published in the English language up to September 2020. 716 items were initially found. After duplicate removal and screening of articles for eligibility criteria, 25 articles published between 2001 and 2019 were selected. Only studies concerning teriparatide, strontium ranelate, sclerostin antibodies and DKK1 antibodies met the eligibility criteria. In particular, only for teriparatide were there both clinical studies and experimental studies available, while for other bone anabolic drugs only animal studies were found. Available evidence about the use of bone anabolic drugs in periodontology demonstrates beneficial effects of these agents on biological pathways and histological parameters involved in periodontal tissue regeneration that suggest relevant clinical implications for the management of periodontitis.

New insights on metal allergy in total joint arthroplasty.

Metal allergy is an uncommon and not completely understood cause of failure in total joint arthroplasty (TJA). However, either immunopathology neither histologic studies clarified the mechanisms through which the metal ions could lead to the complications related to them. The lack of evidence around this topic also reflects the difficulties to diagnose the MRP in TJA. In fact, the diagnosis is generally based on the exclusion of other causes. Currently, skin-patch testing and lymphocyte transformation test (LTT) are being commonly used to investigate about metal hypersensitivity and a delayed type-IV hypersensitivity is the immuno-histologic response to metals involved in TJA loosening. A review of the recent publications about this topic has been made focusing on immunology, histopathology, and clinics to better understand a still debated topic in orthopedic practice.

Fault lubrication during earthquakes.

The determination of rock friction at seismic slip rates (about 1 m s(-1)) is of paramount importance in earthquake mechanics, as fault friction controls the stress drop, the mechanical work and the frictional heat generated during slip. Given the difficulty in determining friction by seismological methods, elucidating constraints are derived from experimental studies. Here we review a large set of published and unpublished experiments (∼300) performed in rotary shear apparatus at slip rates of 0.1-2.6 m s(-1). The experiments indicate a significant decrease in friction (of up to one order of magnitude), which we term fault lubrication, both for cohesive (silicate-built, quartz-built and carbonate-built) rocks and non-cohesive rocks (clay-rich, anhydrite, gypsum and dolomite gouges) typical of crustal seismogenic sources. The available mechanical work and the associated temperature rise in the slipping zone trigger a number of physicochemical processes (gelification, decarbonation and dehydration reactions, melting and so on) whose products are responsible for fault lubrication. The similarity between (1) experimental and natural fault products and (2) mechanical work measures resulting from these laboratory experiments and seismological estimates suggests that it is reasonable to extrapolate experimental data to conditions typical of earthquake nucleation depths (7-15 km). It seems that faults are lubricated during earthquakes, irrespective of the fault rock composition and of the specific weakening mechanism involved.

An empirically based steady state friction law and implications for fault stability.

Empirically based rate-and-state friction laws (RSFLs) have been proposed to model the dependence of friction forces with slip and time. The relevance of the RSFL for earthquake mechanics is that few constitutive parameters define critical conditions for fault stability (i.e., critical stiffness and frictional fault behavior). However, the RSFLs were determined from experiments conducted at subseismic slip rates (V < 1 cm/s), and their extrapolation to earthquake deformation conditions (V > 0.1 m/s) remains questionable on the basis of the experimental evidence of (1) large dynamic weakening and (2) activation of particular fault lubrication processes at seismic slip rates. Here we propose a modified RSFL (MFL) based on the review of a large published and unpublished data set of rock friction experiments performed with different testing machines. The MFL, valid at steady state conditions from subseismic to seismic slip rates (0.1 µm/s < V < 3 m/s), describes the initiation of a substantial velocity weakening in the 1-20 cm/s range resulting in a critical stiffness increase that creates a peak of potential instability in that velocity regime. The MFL leads to a new definition of fault frictional stability with implications for slip event styles and relevance for models of seismic rupture nucleation, propagation, and arrest.

Fluid pressurisation and earthquake propagation in the Hikurangi subduction zone.

In subduction zones, seismic slip at shallow crustal depths can lead to the generation of tsunamis. Large slip displacements during tsunamogenic earthquakes are attributed to the low coseismic shear strength of the fluid-saturated and non-lithified clay-rich fault rocks. However, because of experimental challenges in confining these materials, the physical processes responsible for the coseismic reduction in fault shear strength are poorly understood. Using a novel experimental setup, we measured pore fluid pressure during simulated seismic slip in clay-rich materials sampled from the deep oceanic drilling of the Papaku thrust (Hikurangi subduction zone, New Zealand). Here, we show that at seismic velocity, shear-induced dilatancy is followed by pressurisation of fluids. The thermal and mechanical pressurisation of fluids, enhanced by the low permeability of the fault, reduces the energy required to propagate earthquake rupture. We suggest that fluid-saturated clay-rich sediments, occurring at shallow depth in subduction zones, can promote earthquake rupture propagation and slip because of their low permeability and tendency to pressurise when sheared at seismic slip velocities.

Frictional Melting in Hydrothermal Fluid-Rich Faults: Field and Experimental Evidence From the Bolfín Fault Zone (Chile).

Tectonic pseudotachylytes are thought to be unique to certain water-deficient seismogenic environments and their presence is considered to be rare in the geological record. Here, we present field and experimental evidence that frictional melting can occur in hydrothermal fluid-rich faults hosted in the continental crust. Pseudotachylytes were found in the >40 km-long Bolfín Fault Zone of the Atacama Fault System, within two ca. 1 m-thick (ultra)cataclastic strands hosted in a damage-zone made of chlorite-epidote-rich hydrothermally altered tonalite. This alteration state indicates that hydrothermal fluids were active during the fault development. Pseudotachylytes, characterized by presenting amygdales, cut and are cut by chlorite-, epidote- and calcite-bearing veins. In turn, crosscutting relationship with the hydrothermal veins indicates pseudotachylytes were formed during this period of fluid activity. Rotary shear experiments conducted on bare surfaces of hydrothermally altered rocks at seismic slip velocities (3 m s-1) resulted in the production of vesiculated pseudotachylytes both at dry and water-pressurized conditions, with melt lubrication as the primary mechanism for fault dynamic weakening. The presented evidence challenges the common hypothesis that pseudotachylytes are limited to fluid-deficient environments, and gives insights into the ancient seismic activity of the system. Both field observations and experimental evidence, indicate that pseudotachylytes may easily be produced in hydrothermal environments, and could be a common co-seismic fault product. Consequently, melt lubrication could be considered one of the most efficient seismic dynamic weakening mechanisms in crystalline basement rocks of the continental crust.

Effects of saliva substitutes on oral status in patients with Type 2 diabetes.

AIMS: To assess oral status in a sample of Type 2 diabetic patients before and after therapy with saliva substitutes and oral status in a control group of diabetic patients who were not given saliva substitutes. METHODS: Salivary flow rate was determined in 134 patients (mean age 47.9 ± 2.9 years) with Type 2 diabetes. Mean salivary rate was significantly low compared with a healthy control group. The sample of 134 patients was randomly divided into two groups of 67 people each. One group was given immunologically active salivary substitutes for 6 months, the other group was given nothing. Each patient of the two groups underwent a dental and periodontal examination at the beginning of the study and 6 months later. RESULTS: As regards carious teeth and teeth loss, there was no statistical difference between the first group after 6 months of treatment with salivary substitutes and the control group (P>0.01). Salivary substitutes did not significantly reduce the periodontal disease (P>0.01). In the group treated with salivary substitutes, after 6 months of therapy, the average dental plaque index decreased from 2.3 ± 0.73 to 1.6 ± 0.56, patients with gingivitis decreased from 66 to 43% and patients with positive yeast counts decreased from 60 to 37%. These differences were statistically significant (P<0.01). CONCLUSIONS: In Type 2 diabetes, in the case of hyposalivation, a therapy with immunologically active saliva substitutes can be of help in reducing the amount of plaque, gingivitis and positive yeast counts.

Subseismic to Seismic Slip in Smectite Clay Nanofoliation.

Smectite clays are the main constituent of slipping zones found in subduction zone faults at shallow depth (e.g., <1-km depth in the Japan Trench) and in the decollements of large landslides (e.g., 1963 landslide, Vajont, Italy). Therefore, deformation processes in smectite clays may control the mechanical behavior from slow creep to fast accelerations and slip during earthquakes and landslides. Here, we use (1) laboratory experiments to investigate the mechanical behavior of partly water-saturated smectite-rich gouges sheared from subseismic to seismic slip rates V and (2) nanoscale microscopy to study the gouge fabric. At all slip rates, deformation localizes in volumes of the gouge layer that contain a "nanofoliation" consisting of anastomosing smectite crystals. "Seismic" nanofoliations produced at V = 0.01, 0.1, and 1.3 m/s are similar to "subseismic" nanofoliations obtained at V = 10-5 m/s. This similarity suggests that frictional slip along water-lubricated smectite grain boundaries and basal planes may occur from subseismic to seismic slip rates in natural smectite-rich faults. Thus, if water is available along smectite grain boundaries and basal planes, nanofoliations can develop from slow to fast slip rates. Still, when nanofoliations are found highly localized in a volume, they can be diagnostic of slip that occurred at rates equal or larger than 0.01 m/s. In such a case, they could be markers of past seismic events when found in natural fault rocks.

Mechanical behaviour of fluid-lubricated faults.

Fluids are pervasive in fault zones cutting the Earth's crust; however, the effect of fluid viscosity on fault mechanics is mainly conjectured by theoretical models. We present friction experiments performed on both dry and fluid-permeated silicate and carbonate bearing-rocks, at normal effective stresses up to 20 MPa, with a slip-rate ranging between 10 µm/s and 1 m/s. Four different fluid viscosities were tested. We show that both static and dynamic friction coefficients decrease with viscosity and that dynamic friction depends on the dimensionless Sommerfeld number (S) as predicted by the elastohydrodynamic-lubrication theory (EHD).Under favourable conditions (depending on the fluid viscosity (η), co-seismic slip-rate (V), fault geometry (L/H02) and earthquake nucleation depth (∝σeff)), EHD might be an effective weakening mechanism during natural and induced earthquakes. However, at seismic slip-rate, the slip weakening distance (Dc) increases markedly for a range of fluid viscosities expected in the Earth, potentially favouring slow-slip rather than rupture propagation for small to moderate earthquakes.

Two-stage reimplantation in periprosthetic knee infection.

OBJECTIVE: The increasing number of total knee arthroplasties performed yearly worldwide has resulted in a concomitant rise in bacterial infections. Two-stage reimplantation has been reported as the most successful method of treating periprosthetic knee infections. The purpose of this study was to describe all the phases of the two-stage reimplantation and to review the literature regarding the topic. MATERIALS AND METHODS: Most significant and recent papers about the management of periprosthetic knee infection through a two-stage reimplantation protocol were carefully analysed and reviewed. Our personal experience, previously published, with two-stage-reimplantation protocol was also briefly reported. RESULTS: Two-stage reimplantation has been reported as the most successful method of treating periprosthetic knee infections. The strategy of using an antibiotic-loaded cement spacer and intravenous antibiotics with delayed exchange arthroplasty is actually considered the state-of-the-art, with a reported success rate of 88-96%. The two-stage protocol has been reported as a viable option also for patients with a periprosthetic knee infection by multidrug-resistant organisms. On the other hand, open debridement with polyethylene exchange and single-stage reimplantation have been reported effective only in selective case series involving acute infections by low-virulence organisms. CONCLUSIONS: The strategy that involves the use of cement spacer, intravenous antibiotic therapy, and successive revision total knee implantation is nowadays considered the gold standard for the management of the periprosthetic knee infection. This treatment is actually considered the first choice not only for chronic but also for acute infections, especially in the presence of resistant bacteria.

Reduced intensity allogeneic umbilical cord blood transplantation in children and adolescent recipients with malignant and non-malignant diseases.

There is a significant amount of morbidity and mortality following myeloablative umbilical cord blood transplantation (UCBT). Reduced intensity (RI) conditioning offers an alternative to myeloablative conditioning before UCBT. We investigated RI-UCBT in 21 children and adolescents with malignant (n=14), and non-malignant diseases (n=7). RI conditioning consisted of fludarabine (150-180 mg/m2) with either busulfan (< or = 8 mg/kg)+rabbit antithymocyte globulin (R-ATG; n=16) or cyclophosphamide+R-ATG+/-etoposide (n=5). Human leukocyte antigen match: 4/6 (n=13), 5/6 (n=5) and 6/6 (n=3). The median total nucleated cell and CD34+ cell dose per kilogram were 3.58 x 10(7) and 2.54 x 10(5), respectively. The median time for neutrophil and platelet engraftment was 17.5 and 52 days, respectively. There were six primary graft failures (chronic myelogenous leukemia (CML), beta-thalassemia, hemophagocytic lymphohistiocytosis (HLH) and myelodysplastic syndrome (MDS)). The probability of developing grade II to grade IV acute graft-versus-host disease (GVHD) and chronic GVHD was 28.6 and 16.7%, respectively. Incidence of transplant-related mortality (TRM) was 14%. The 5 years overall survival (OS) in all patients was 59.8%. The 5 years OS for patients with average versus poor-risk malignancy was 77.8 versus 22.2% (P=0.03). RI-UCBT may result in graft failure in specific high-risk chemo-naïve patients (CML, beta-thalassemia, HLH and MDS), but in more heavily pretreated pediatric and adolescent recipients results in rapid engraftment and may be associated with decreased severe GVHD and TRM.

Long-term adherence to first-line highly active antiretroviral therapy in a hospital-based cohort: predictors and impact on virologic response and relapse.

A high level of adherence to highly active antiretroviral therapy (HAART) is essential to minimize the risk of treatment failure and HIV disease progression. This cohort study evaluated the prevalence and predictors of long-term adherence with first-line HAART in a hospital-based unselected sample of HIV patients from central Italy, and examined the association between adherence and virological response or relapse. Between July 1996 and June 2004, 171 patients (67.3% males; mean age, 41.2 years) were followed for at least 24 weeks and up to 8 years. Adherence was measured by patient self-reports and confirmed using pharmacy records. The prevalence of high-level adherence (>or=90%) at 6 months was 88.3%; slightly less than 80% at 12 months. The incidence of adherence failure in the sample remained fairly stable until 24 months of follow-up, then it declined about 5% every 6 months. Cox analysis showed that compared to single/separated patients, homeless and married persons were, respectively, 1.95 times more likely and two times less likely to experience adherence failure (p < 0.05). The adjusted risk of adherence failure among patients who did not suffer drug-related toxicity was 0.57 (p < 0.05). Medication adherence was significantly associated with shorter time to virological response and longer time to relapse. Adherents were 1.69 times more likely to achieve viral suppression and nine times less likely to experience relapse than nonadherents (p < 0.01). Efforts at improving adherence should be prolonged for at least 24 months. A protective role of marriage for adherence failure is promising but requires confirmation in further research, that should also clarify the exact mechanisms determining the association.

G: Fracture energy, friction and dissipation in earthquakes.

Recent estimates of fracture energy G' in earthquakes show a power-law dependence with slip u which can be summarized as G' ∝ ua where a is a positive real slightly larger than one. For cracks with sliding friction, fracture energy can be equated to Gf : the post-failure integral of the dynamic weakening curve. If the dominant dissipative process in earthquakes is friction, G' and Gf should be comparable and show a similar scaling with slip. We test this hypothesis by analyzing experiments performed on various cohesive and non-cohesive rock types, under wet and dry conditions, with imposed deformation typical of seismic slip (normal stress of tens of MPa, target slip velocity > 1 m/s and fast accelerations ≈ 6.5 m/s2). The resulting fracture energy Gf is similar to the seismological estimates, with Gf and G' being comparable over most of the slip range. However, Gf appears to saturate after several meters of slip, while in most of the reported earthquake sequences, G' appears to increase further and surpasses Gf at large magnitudes. We analyze several possible causes of such discrepancy, in particular, additional off-fault damage in large natural earthquakes.

Cerebral malaria. A disseminated vasculomyelinopathy.

Neuropathologic examination of 19 fatal cases of cerebral malaria and a review of the literature showed that the epidemiologic, clinical, and pathologic features of this entity suggest consideration of cerebral malaria as a form of disseminated vasculomyelinopathy, a hyperegic reaction of the CNS to the antigenic challenge of Plasmodium falciparum infection. Experimental evidence also substantiates this view The initial event seems to be vasculopathy, with alteration of the endothelial permeability, followed by brain edema, perivascular infiltrates and ring hemorrhages, perivascular demyelination, and gliosis (malarial granuloma) in the late stages. This chain of events could be interrupted early in its course by corticosteroids. Parenteral dexamethasone should then be seriously considered at the first signs of involvement of the CNS during P falciparum malaria along with the standard forms of antimalarial therapy.

Neuroparalytic accidents of antirabies vaccination with suckling mouse brain vaccine. Clinical and pathologic study of 21 cases.

Twenty-one cases of neuroparalytic accidents of rabies vaccination (with suckling mouse brain vaccine), 11 of them fatal, were observed, occurring predominantly in men; the mean age of the patients was 29 years. On the average, 13 doses of the vaccine were used. Only three patients received less than seven doses. The mean latent period was 14 days (range, 4 to 24 days). In 16 patients (76%), a Guillain-Barré syndrome occurred that was moderate in three, severe in seven, and fatal in six. Pathologically, this was shown to be a typical polyradiculoneuritis. Five patients had fatal involvement of the central nervous system. Three had an acute disseminated perivenous leukoencephalopathy, with concurrent rabies encephalitis in one case. One patient had a perivenous myeloradiculopathy and one a chronic encephalomyelopathy of six years' duration with demyelinating plaques in the periventricular white matter, cerebellum, and spinal cord. Since the reduction of postexposure rabies vaccination to seven doses, no new cases have been observed in Colombia.

Herpetic brainstem encephalitis.

A fatal case of brainstem encephalitis presented as an acute lateral medullary syndrome. Pathologic examination showed a focal encephalitis along the roots and the intramedullary portion of the right vagus and glossopharyngeal nerves. Herpesvirus particles were demonstrated by electronmicroscopy of formol-fixed material. This is the second known case of herpetic brainstem encephalitis confirmed by postmortem examination and the only one in which the infection was limited to the brainstem. This case and a review of previously reported cases suggest that the viral infection could proceed to the brainstem through the vagus and glossopharyngeal nerves, probably from a source of latent herpetic infection in the respective ganglia.

A gene family encoding heterogeneous histone H1 proteins in Trypanosoma cruzi.

A gene family encoding a set of histone H1 proteins in Trypanosoma cruzi is described. The sequence of 3 genomic and 4 cDNA clones revealed the presence of several motifs characteristic of histone H1, although heterogeneity at the polypeptide level was evident. The clones encode histone H1 proteins of an unusually small size (74-97 amino acids), which lack the globular domain found in histone H1 of higher eukaryotes. All histone H1 mRNAs from T. cruzi are polyadenylated, although no typical polyadenylation signal was found. Furthermore, the genes encoding the histone H1 proteins in T. cruzi are found in a tandem array containing 15-20 gene copies per haploid genome. This tandem array is located on a large chromosome of 2.2 Mb.

Outcomes of unrelated cord blood transplantation in pediatric recipients.

We report results of unrelated cord blood transplants (UCBT) in 29 pediatric recipients in one center and the risk factors associated with survival. Median age: 9 years (0.5-20); diagnosis: ALL (9), AML (4), CML (1), HD (3), HLH (1), NHL (3), NBL (2); B-thal (1), FA (1), FEL (1), Krabbe (1), WAS (1), SAA (1); median follow-up: 11 months; conditioning: total body irradiation (TBI)-ablative (14), chemotherapy-ablative (6) and reduced intensity chemotherapy (9); GVHD prophylaxis: MMF/FK506 (18), cyclosporin A (CsA)+steroids+/-MMF (7) or CsA+methotrexate (MTX) (4); median total nucleated cells (TNC): 3.8 x 10(7)/kg (1.1-11); median CD34+: 2.3 x 10(5)/kg (0.2-9.9); and HLA match: 2 (6/6), 5 (5/6), 22 (4/6). Neutrophil engraftment by cumulative incidence curves 63% (median 28 (95% confidence interval (CI) 18-32)). Probability of >/=grade II acute graft-versus-host disease (aGVHD) by day +60 27%, >/=grade III aGVHD 20% and chronic graft-versus-host disease 3%. Estimated 1-year overall survival (OS) 46% (95% CI 30-71) and standard risk 60% (95% CI 29-100%). Variables associated with improved survival by multivariate analysis include non-TBI-ablative conditioning (P=0.024), CD34+/kg (P=0.038) and gender (P=0.048). These results suggest that CD34/kg cell dose and non-TBI-ablative conditioning may be important variables influencing OS following UCBT in pediatric recipients. Given the small number of patients, these results should be viewed cautiously.

A pilot study of reduced intensity conditioning and allogeneic stem cell transplantation from unrelated cord blood and matched family donors in children and adolescent recipients.

Reduced intensity (RI) allogeneic stem cell transplantation (AlloSCT) was initially demonstrated in adults following HLA-matched family and unrelated adult donor AlloSCT. There is little information about RI AlloSCT in children. We report results of a pilot study of RI AlloSCT in 21 recipients (< or =21 years). Age: median 13 (0.5-21) years, 8F:13M, 14 unrelated cord blood units (UCB) (10 4/6, 4 5/6), two related BM (6/6, 5/6), four related PBSC (2 6/6, 2 5/6), and one related BM+PBSC (6/6). RI: fludarabine, busulfan (n=14); fludarabine, cyclophosphamide (n=4); fludarabine, melphalan (n=1); total body irradiation, fludarabine, cyclophosphamide (n=1); or fludarabine, cyclophosphamide, and etoposide (n=1). Graft-versus-host disease prophylaxis: FK506 0.03 mg/kg/day and mycophenolate mofetil 15 mg/kg/q 12 h. UCB median nuc/kg and CD34/kg was 4.3 x 10(7)/kg (0.9-10.8) and 1.9 x 10(5)/kg (0.3-6.9), and related BM/PBSC median nuc/kg and CD34/kg was 8.3 x 10(8) (4.7-18.9) and 5.0 x 10(6)/kg (4.6-6.4). Maximal chimerism following unrelated cord blood transplantation, 100% x 7, 98% x 1, 95% x 2, 55% x 1, and 0% x 3; related PBSC/BM, 100% x 5, 65% x 1, and 55% x 1. Graft failure occurred in 5/21 (24%). In summary, RI AlloSCT in children is feasible and tolerable (< or =25% GF) and results in > or =85% of recipients initially achieving > or =50% donor chimerism.

Primary angiitis of the central nervous system: report of five biopsy-confirmed cases from Colombia.

INTRODUCTION: Primary (isolated) angiitis of the central nervous system (PACNS) is a rare cause of cerebrovascular disease (CVD), and few leptomeningeal and brain biopsy (LBB)-confirmed cases have been reported from South America. METHODS: We retrospectively reviewed charts of patients with diagnosis of cerebral angiitis admitted between March 1991 and July 2001 to a single university hospital in Medellin, Colombia. Patients with definitive diagnosis of PACNS by Alrawi et al.'s LBB criteria were selected. We excluded other causes of cerebral angiitis as well as cases without LBB confirmation. RESULTS: We report five patients, four men and one woman, with a mean age at onset of 24.4 years, and an average disease progression of 12.4 days. Four presented with headache and motor weakness, three had seizures, and two had alterations of consciousness. Cerebral MRI was abnormal in all five cases; brain CT in four, and cerebral angiography in two. The cerebrospinal fluid (CSF) was abnormal in two patients. Leptomeningeal and brain biopsies revealed mononuclear infiltration in the wall of small blood vessels in all. Three had concurrent meningeal and cerebral involvement, two had necrotizing angiitis, and one had vascular and encephalitic lesions. All received only steroid treatment; the 1-year follow-up revealed good prognosis without relapses. CONCLUSION: We report five biopsy-proven cases of PACNS from Colombia associated with neurological and neuroimaging abnormalities; these patients presented a mild inflammatory disease that was correlated with few CSF abnormalities and good response to single steroid treatment without relapses. Leptomeningeal and brain biopsy is mandatory for a definitive diagnosis.