Dem-Aging: autophagy-related pathologies and the "two faces of dementia".

Neuronal ceroid lipofuscinosis (NCL) is an umbrella term referring to the most frequent childhood-onset neurodegenerative diseases, which are also the main cause of childhood dementia. Although the molecular mechanisms underlying the NCLs remain elusive, evidence is increasingly pointing to shared disease pathways and common clinical features across the disease forms. The characterization of pathological mechanisms, disease modifiers, and biomarkers might facilitate the development of treatment strategies.The DEM-AGING project aims to define molecular signatures in NCL and expedite biomarker discovery with a view to identifying novel targets for monitoring disease status and progression and accelerating clinical trial readiness in this field. In this study, we fused multiomic assessments in established NCL models with similar data on the more common late-onset neurodegenerative conditions in order to test the hypothesis of shared molecular fingerprints critical to the underlying pathological mechanisms. Our aim, ultimately, is to combine data analysis, cell models, and omic strategies in an effort to trace new routes to therapies that might readily be applied in the most common forms of dementia.

Calcitonin levels in autoimmune atrophic gastritis-related hypergastrinemia.

PURPOSE: Calcitonin (Ct) is currently the most sensitive biochemical marker of C-cell disease (medullary thyroid cancer [MTC] and C-cell hyperplasia), but its specificity is relatively low. Our aim was to examine whether autoimmune atrophic gastritis (AAG) and chronic hypergastrinemia, with or without chronic autoimmune thyroiditis (AT), are conditions associated with increased Ct levels. METHODS: Three groups of patients were consecutively enrolled in this  multicentric study: group A consisted of patients with histologically-proven AAG (n = 13; 2 males, 11 females); group B fulfilled the criteria for group A but also had AT (n = 92; 15 males, 77 females); and group C included patients with AT and without AAG (n = 37; 6 males, 31 females). RESULTS: Median Ct levels did not differ between the three groups. Ct levels were undetectable in: 8/13 cases (61.5%) in group A, 70/92 (76.1%) in group B, and 27/37 (73.0%) in group C. They were detectable but ≤ 10 ng/L in 4/13 (30.8%), 20/92 (21.7%) and 7/37 (18.9%) cases, respectively; and they were > 10 ng/L in 1/13 (7.7%), 2/92 (2.2%) and 3/37 (8.1%) cases, respectively (P = 0.5). Only three patients had high Ct levels (> 10 ng/L) and high gastrin levels and had an MTC. There was no correlation between Ct and gastrin levels (P = 0.353, r = 0.0785). CONCLUSIONS: High gastrin levels in patients with AAG do not explain any hypercalcitoninemia, regardless of whether patients have AT or not. This makes it mandatory to complete the diagnostic process to rule out MTC in patients with high Ct levels and AAG.

Autofluorescence of parathyroid glands during endocrine surgery with minimally invasive technique.

PURPOSE: Accidental injury to the parathyroid glands (PTGs) is common during thyroid and parathyroid surgery. To overcome the limitation of naked eye in identifying the PTGs, intraoperative autofluorescence imaging has been embraced by an increasing number of surgeons. The aim of our study was to describe the technique and assess its utility in clinical practice. METHODS: Near-infrared (NIR) autofluorescence imaging was carried out during open parathyroid and thyroid surgery in 25 patients (NIR group), while other 26 patients underwent traditional PTG detection based on naked eye alone (NO-NIR group). Primary variables assessed for correlation between traditional approach and autofluorescence were number of PTGs identified and incidence of postoperative hypoparathyroidism (hypoPT). RESULTS: 81.9% of PTGs were detected by means of fluorescence imaging and 74.5% with visual inspection alone, with an average of 2.72 PTGs visualized per patient using NIR imaging versus approximately 2.4 per patient using naked eye (p = 0.38). Considering only the more complex total thyroidectomies (TTs), the difference was almost statistically significant (p = 0.06). Although not statistically significant, the observed postoperative hypoPT rate was lower in the NIR group. CONCLUSION: Despite the limitations and technical aspects still to be investigated, fluorescence seems to reduce this complication rate by improving the intraoperative detection of the PTGs.

Maxillary sinusitis caused by retained dental impression material: An unusual case report and literature review.

Surgical procedures in posterior area of maxillary might cause an oroantral communication and iatrogenic sinusitis. An undetected oroantral communication can cause the penetration of foreign bodies, such as dental impression materials, in the maxillary sinus, thereby contributing to persistent sinusitis. Given the occurrence of a very rare clinical and medicolegal case of persistent and drug-resistant sinusitis due to radiologically undetected fragments of silicone paste for dental impression in the maxillary antrum, a literature review was pursued through sensitive keywords in relevant databases for health sciences. All retrieved articles were considered and data about the kind of impression materials thrusted into the maxillary sinus, the diagnostic issues, the reported range of symptoms, and the occurrence of medicolegal issues were analyzed. The diagnosis resulted to be quite challenging and belatedly especially in case of healed oroantral communication and when the material retained in the maxillary sinus has similar radiodensity compared to the surrounding normal or inflammatory tissues. The case was then discussed in comparison with the reviewed literature for both clinical and medicolegal issues. Hints were provided to professionals to face the challenging diagnosis in similar rare cases and to avoid the possible related litigation.

Comparative surface detail reproduction for elastomeric impression materials: Study on reproducibility performance.

For dental impression of a prepared tooth, the goal is a void-free negative representation from which an accurate cast of a tooth and its surrounding tissue can be reproduced. This in-vitro study assessed and compared the reproduction accuracies of surface detail obtained with three different dental elastomeric impression materials: vinyl polysiloxane (VPS), vinyl polyether silicone (VPES), and polyether (PE). A stainless-steel model with two abutments was used, with impressions taken 10 times for each material, for 20 abutment impressions per group, using a two-phase, one-step technique (heavy body/light body). The impressions were removed and assessed for numbers of enclosed voids and open voids visible on the surface. The defect frequency was 95% for impressions with the VPS and VPES materials, and 30% for the PE material. No significant differences were seen for number of impressions with defects for VPS versus VPES. Significant differences were seen for VPS and VPES versus the PE material (P <.05). No significant differences were seen for the defect type distributions across these three impression materials. The PE impression material showed better accuracy for reproduction of surface detail of these dental impressions compared to the VPS and VPES impression materials.

Missed opportunities to prevent mother-to-child transmission of HIV in Italy.

OBJECTIVES: Vertical transmission of HIV can be effectively controlled through antenatal screening, antiretroviral treatment and the services provided during and after childbirth for mother and newborn. In Italy, the National Health Service guarantees universal access to prenatal care for all women, including women with HIV infection. Despite this, children are diagnosed with HIV infection every year. The aim of the study was to identify missed opportunities for prevention of mother-to-child transmission of HIV. METHODS: The Italian Register for HIV Infection in Children, which was started in 1985 and involves 106 hospitals throughout the country, collects data on all new cases of HIV infection in children. For this analysis, we reviewed the database for the period 2005 to 2015. RESULTS: We found 79 HIV-1-infected children newly diagnosed after birth in Italy. Thirty-two of the mothers were Italian. During the pregnancy, only 15 of 19 women with a known HIV diagnosis were treated with antiretroviral treatment, while, of 34 women who had received an HIV diagnosis before labour began, only 23 delivered by caesarean section and 17 received intrapartum prophylaxis. In 25 mothers, HIV infection was diagnosed during pregnancy or in the peripartum period. Thirty-one newborns received antiretroviral prophylaxis and 39 received infant formula. CONCLUSIONS: We found an unacceptable number of missed opportunities to prevent mother-to-child transmission (MCTC). Eliminating HIV MTCT is a universal World Health Organization goal. Elucidating organization failures in Italy over the past decade should help to improve early diagnosis and to reach the zero transmission target in newborns.

Soft tissue augmentation by means of silicon expanders prior to bone volume increase: a case series.

In guided bone regeneration (GBR) interventions, the incorrect manipulation of the soft tissues may lead to exposure of graft due to insufficient amount of tissue needed for a free-tension flap closure. The aim of this investigation was to evaluate the clinical and radiographical effectiveness of soft tissue augmentation in aesthetic areas. A total of 6 patients were treated in the Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio" of Chieti-Pescara, with a radiographical follow-up at 1 year from the loading. At the follow up, no soft tissue dehiscence was observed This study presented an innovative approach for soft tissue augmentation prior to bone regeneration in aesthetic areas. Augmentation of soft tissue with a silicon expander device before bone regeneration is a simple technique and also allows to obtain greater bone tissue in selective cases.

Testing the efficacy and efficiency of a single "universal warming protocol" for vitrified human embryos: prospective randomized controlled trial and retrospective longitudinal cohort study.

PURPOSE: To study the efficacy and efficiency of a "universal warming protocol" for vitrified human embryos, based on subsequent steps with 1 and 0.5 M concentration of extracellular cryoprotectant (ECCP). METHOD: Two studies on patients undergoing fertility treatments via ICSI: a prospective randomized controlled trial (RCT) and a retrospective cohort study (CS). SETTING: Private assisted reproductive (AR) center. RCT: duration 01/03/2017-01/10/2017; 315 embryos at blastocyst stage obtained from 169 patients. Each patient's embryos were first randomized for vitrification with two different kits: Vitrification Kit (Kitazato, Japan) and Sage Vitrification Kit (Origio, Denmark). The embryos were randomly warmed with either Kitazato (K) or Sage (S) warming kits, specifically: group A (KK), group B (KS), group C (SK), and group D (SS). PRIMARY OUTCOME MEASURE: survival rate (number of embryos surviving per number of embryos warmed). Secondary: implantation rate (number of embryos implanted per number of embryos transferred). CS: duration 01/01/2013-31/12/2015 embryos from patients' own oocytes; 10/04/2015-31/07/2017 embryos from donors' oocytes. A total of 1055 embryos vitrified at cleavage stage obtained from 631 warming cycles: 847 of these obtained from patients' own oocytes, 208 egg-donation-derived embryos. Each patient's embryos were vitrified and warmed in various combinations of three different vitrification/warming kits: Kitazato (K), Sage (S), or made in-house in our laboratory (H). Vitrification/warming kits from different manufacturers are routinely used in our AR center, and the warming procedures are randomly performed with any available kit on a "first-in-first-out" basis, irrespective of the kit used for vitrification. Group names: KK, KS, SK, SS, SH, HK, HS, HH (embryos from patients' own oocytes); eKK, eKS, eSK, eSS (egg-donation-derived embryos). RESULTS: Cryo-survival rates were comparable in all study groups. RCT. Group A 99.0% (96/97), group B 98.8% (83/84), group C 98.4% (61/62), and group D 98.6% (71/72). CS. Embryos from patients' own oocytes: KK 96.4% (54/56), KS 100.0% (13/13), SK 98.8% (80/81), SS 97.2% (174/179), SH 97.6% (40/41), HK 95.2% (20/21), HS 99.5% (187/188), and HH 97.4% (261/268). Egg-donation-derived embryos: eKK 100.0% (91/91), eKS 98.4% (60/61), eSK 100.0% (26/26), and eSS 96.7 (29/30). Implantation was generally comparable in all study groups-exceptions were in CS: KS vs. SK (P = 0.049), SS (P = 0.012), HS (P = 0.010), HH (P = 0.025); and SH vs. SS (P = 0.042), HS (P = 0.035). CONCLUSION: Worldwide, millions of embryos have been cryopreserved using different vitrification kits; these studies establish that it is possible to combine different kits for vitrification and warming using a universal warming protocol. This can optimize costs, simplify lab routines, and favor embryo exchange between IVF centers. RCT REGISTRATION NUMBER: ISRCTN12342851.

Scanning electron microscopy and microbiological approaches for the evaluation of salivary microorganisms behaviour on anatase titanium surfaces: In vitro study.

Implantology research framed the implant surface as a key element for a good and sustainable osseointegration of an implant fixture. The aim of this study was to analyze the antibacterial properties of anatase-coated titanium healing screws through microbiological and scanning electron microscopy. The comparison of the bacterial colonies growth between the anatase-coated titanium healing screws and non-coated titanium healing screws showed comparable antibacterial properties, without significant statistical differences. The scanning electron microscopy observations confirmed the microbiological study. These data, also considering previous reports on the positive effects on osteoblasts genetic expressions, might suggest a use of the anatase-coated titanium healing screws to preserve the tissues surrounding implants from microbial attacks.

Anti-inflammatory steroid use in impacted third molar surgery: a systematic review.

Oral surgery procedures involve traumatization of mucosal and bony tissues, and lengthy interventions can lead to inflammatory post-operative sequelae. In the bony tissues in particular, the inflammatory processes can affect healing. Modern drug therapies provide valid support for lowering the risk of occurrence of post-operative inflammatory signs. The two main types of agents used are nonsteroidal anti-inflammatory drugs and/or corticosteroids, which act on two different molecular pathways in the inflammatiory process. The aim of this systematic review is to examine the different corticosteroids used in oral surgery procedures, their indications for use, and their route of administration, to provide the clinician with a useful scheme for correct pharmacological management of post-operative inflammation. To identify studies eligible for inclusion in this systematic review, we performed a literature search up to April 2017 of the electronic databases, considering published papers from 2007 to 2017. The search terms included steroids, third molar, oral surgery, RCT [randomized controlled trial], human, and clinical trial. Only articles in English language were considered.

The effects of surgical preparation techniques and implant macro-geometry on primary stability: An in vitro study.

BACKGROUND: The attainment of a good primary stability is a necessary condition to ensure the success of osseointegration in implantology. In type IV cancellous bone, however, it is possible that a reduced primary stability can lead to an increased rate of failure. The aim of this study was therefore to determine, with the help of the resonance frequency (Osstell mentor), which technique of implant site preparation (piezo surgery, conventional, under-preparation, bone compaction, osteodistraction) and macro-geometry is able to improve implant stability in type IV cancellous bone. MATERIAL AND METHODS: 10 pig ribs were prepared with a surgical pre-drilled guide, calibrated for a correct implant positioning. On each rib, 5 implant sites (one for each technique) were prepared. Successively, 50 conical implants (Tekka Global D) were inserted and measured with the resonance frequency to evaluate the primary stability. Data collected were analyzed by analysis of variance (ANOVA) to test whether the Implant Stability Quotient (ISQ) values of the five techniques were significantly different. RESULTS: The results showed that no significant differences among the ISQ values of the five techniques used were found. Also, no significant differences in the macro-geometry of the two types of compared implants were observed. However, the macro-geometry of Tekka implants, characterized by a double condensing thread, seems to provide greater ISQ values than those of single thread implants when using the same technique. CONCLUSIONS: In light of these preliminary data, it is conceivable that in cases of reduced stability, such as those occurring with a type IV bone, all means ameliorating the primary stability and accelerating the osseointegration can be utilized.

Radiofrequency ablation for benign thyroid nodules.

Benign thyroid nodules are an extremely common occurrence. Radiofrequency ablation (RFA) is gaining ground as an effective technique for their treatment, in case they become symptomatic. Here we review what are the current indications to RFA, its outcomes in terms of efficacy, tolerability, and cost, and also how it compares to the other conventional and experimental treatment modalities for benign thyroid nodules. Moreover, we will also address the issue of treating with this technique patients with cardiac pacemakers (PM) or implantable cardioverter-defibrillators (ICD), as it is a rather frequent occurrence that has never been addressed in detail in the literature.

Cone beam computed tomography investigation of the antral artery anastomosis in a population of Central Italy.

BACKGROUND: The arterial vascular supply of maxillary sinus has to be considered in all the surgical procedures where it is involved. In particular, the intraosseous anastomosis between the posterior superior alveolar artery and the infraorbital artery branches in the bony canal can be tricky to a not well aware clinician. The aim of this study is to investigate the arterial blood supply of the maxillary sinus to give clinicians the basis for a better understanding of vascular complications that can derive from surgical procedures at this level. MATERIALS AND METHODS: One hundred cone beam computed tomography were analysed by the Imaging software for three-dimensional images, i-Dixel 2.0. The parameters considered have been the presence (i), the calibre (ii), the dorso-ventral length (iii) and the cranio-caudal distance (iv). The data have been processed with means, standard deviations and verified by T-Student test. RESULTS: The statistical outputs showed that the 38% of samples presented the intraosseous anastomosis. Those anastomosis resulted long in dorso-ventral way both on left (12.55 ± 4.3 mm) and right side (12.4 ± 4.3 mm). The mean cranio- -caudal distance resulted 15.71 ± 5.08 mm on the left and 14.73 ± 4.74 mm on right side. The calibre measurements resulted quite big as well: 1.68 ± 0.3 mm on the left and 1.54 ± 0.38 mm on the right. The differences between the right and left sides were found not statistically significant. CONCLUSIONS: This in vivo investigation shows how a knowledge of the maxillary sinus vascularisation is essential during the programming surgical phase in order to prevent blood complications during the operations involving this region. (.

The process of mineralisation in the development of human tooth.

AIM: Tooth development and mineralisation are processes that derive from different tissues interactions, in particular ectodermal and mesenchymal layers. These interactions are responsible for the formation of unique structures with a particular chemical composition. Despite differences, mineralised tissues are similar and they derive by highly concerted extracellular processes that involve matrix proteins, proteases, and mineral ion fluxes that collectively regulate the nucleation, growth and organisation of forming mineral crystals. This review aims at explaining mineralisation, its stages and when damage occurs and alters the hard tissues structure.

Cross-sex hormone therapy for gender dysphoria.

PURPOSE: Gender identity is the sense one has of being male or female. Gender dysphoria (GD) refers to the distress caused by the incongruence between gender identity and biological sex in gender-nonconforming individuals. Cross-sex hormone therapy (CHT) aims at easing GD, improving well-being, and quality of life of gender-nonconforming individuals. This can be achieved by inducing and maintaining the desired-sex characteristics in accordance with the specific aspirations and expectations of each individual. Nevertheless, CHT can be associated with potentially serious long-term complications. METHODS: Here, we review when, how, and how long to prescribe CHT to adult transsexuals as well as what to expect and monitor once it has been initiated. RESULTS: In recent years, transsexualism has become more and more recognized and depathologized. To manage GD, National and International Standards of Care have been established. Nevertheless, the needs of transgender patients can still be ignored or dismissed. Moreover, some questions remain unanswered because of the lack of specific retrospective or prospective studies on CHT. CONCLUSION: Education and culturally sensitive training must be supplied to healthcare professionals to overcome the existing issues on GD management and change the perspectives of transsexual people.

Isolated axillary nodal swelling and cancer of unknown primary.

INTRODUCTION: The literature reports rare cases of isolated axillary lymph node metastasis from cancer of unknown primary (CUP). The authors reviewed the prevalence and outcome of patients with isolated axillary nodal swelling suspicious for malignancy affected or not by isolated axillary node metastasis from CUP. MATERIALS AND METHODS: The authors collected data about 65 patients presented with isolated axillary lymph node swelling who underwent axillary lymph node excisional biopsy for malignancy suspicion, between January 2005 and December 2011, in the absence of any specific diagnosis. RESULTS: Histological examination revealed a metastatic infiltration by an occult solid cancer in 16 cases (24%), ten of which were occult breast cancers. Histological patterns and molecular markers allowed in all cases of occult cancer a probable identification of the primary tumor site, while a definitive diagnosis was possible only in the 56.25% of cases (9/16). The prognosis of these patients was very poor with a five-year overall survival of 28%, and thus very similar to patients affected by Stage IV overt breast cancer. CONCLUSIONS: Among occult malignancies presenting with sole axillary lymph node metastasis, breast cancer remains the more probable primary cancer, but many other sites should be taken into consideration by negative breast imaging. Positron-emission tomography computed tomography (PET-CT) resulted helpful in the primary site detection, but has nonetheless a margin of failure. Occult breast cancers behave very similar to Stage IV overt breast cancers, and should be treated accordingly.

Laparoscopic peritoneal lavage for perforated colonic diverticulitis: a definitive treatment? Retrospective analysis of 63 cases.

BACKGROUND: The ideal treatment of perforated diverticulitis and the indications for elective colon resection remain controversial. Considering the significant morbidity and mortality rates related to traditional resection, efforts have been made to reduce the invasiveness of surgery in recent decades. Laparoscopic peritoneal lavage has emerged as an effective alternative option. We retrospectively investigated the effectiveness of laparoscopic peritoneal lavage for perforated diverticulitis and the possibility that it could be a definitive treatment. METHODS: We included patients treated with laparoscopic peritoneal lavage for perforated diverticulitis. The inclusion criteria were all emergency patients with generalized peritonitis due to Hinchey III perforated diverticulitis and some cases of Hinchey II and IV. RESULTS: Sixty-three patients were treated with laparoscopic peritoneal lavage. Six patients (9.5 %) had Hinchey II diverticulitis; 54 patients (85.7 %) had Hinchey III; and three patients (4.8 %) had Hinchey IV. The mean operative time was 87.3 min (±25.4 min), and the overall morbidity rate was 14.3 %. One patient died because of pulmonary embolism, and there were six early reinterventions because of treatment failure. Delayed colon resection was performed in four of the remaining 57 patients (7 %) because of recurrent diverticulitis. In the other 53 patients (93 %), we saw no recurrence of diverticulitis and no intervention was performed after a median follow-up period of 54 months (interquartile range 27-98 months). CONCLUSIONS: Laparoscopic peritoneal lavage for perforated diverticulitis can be considered a safe and effective alternative to traditional surgical resection, and using this approach, most elective colon resection might be avoided.

A specific Toll-like receptor profile on T lymphocytes and values of monocytes correlate with bacterial, fungal, and cytomegalovirus infections in the early period of allogeneic stem cell transplantation.

BACKGROUND: Bacterial, fungal, and viral infections often affect non-relapse mortality after allogeneic stem cell transplantation (alloSCT). Recovery from infections depends on a balanced integration between innate and adaptive immune responses. In this complex interplay, a key role is played by Toll-like receptors (TLRs), which are sensors of pathogen-associated molecular patterns. To our knowledge, no previous study deals with both expression and function of all human TLRs together, in relation to infections in the setting of alloSCT. METHODS: We prospectively evaluated 9 TLRs by flow cytometry on T lymphocytes and monocytes of 35 patients in relation to infectious events from day +30 to day +120. Tumor necrois factor-alpha, interleukin-4, interferon-gamma, and monocyte chemoattractant protein-1 induction upon TLR activation was assessed by enzyme-linked immunosorbent assay on cell supernatants. RESULTS: In multivariate Cox regression analysis, levels of TLR-9 expression on T lymphocytes (P = 0.01) and values of natural killer cells (P = 0.01) correlated negatively with bacterial infections, whereas cytomegalovirus (CMV) infection resulted as a positive predictor. We observed a trend for negative correlation between TLR-7 levels on T lymphocytes and fungal infections (P = 0.07). Values of monocytes were negatively associated with CMV infection (P = 0.03), whereas levels of TLR-5 on T lymphocytes were positive predictors (P = 0.01). Age (P = 0.03) and bacterial infections (P = 0.006) negatively influenced overall survival. Monocyte values were positive predictors of survival (P = 0.003). CONCLUSIONS: Bacterial, fungal, and CMV infections were associated with a different expression of some TLRs on T lymphocytes. The protective role of TLR-7 and TLR-9 seemed dominant over other TLRs involved in recognizing fungi and bacteria. We also observed an atypical involvement of TLR-5 in CMV infection. The dominant and atypical role of some TLRs could depend on their pleiotropic functions and the changing inflammatory environment of transplanted patients. A specific TLR profile and an adequate count of monocytes could improve survival, promoting an effective control of infections, and balanced immune responses. If our findings will be confirmed by further studies, these immunological variables could be useful as parameters to predict susceptibility to infections.