Line-Field Confocal Optical Coherence Tomography Evaluation of Eyelid Skin Lesions.

BACKGROUND: Periocular malignancies may be clinically different from the examples arising at other sites, with possible delayed diagnosis and greater challenges for treatment and repair. Line-field confocal optical coherence tomography (LC-OCT) is a recently developed technique characterized by an unprecedented capacity to acquire high-definition images in vertical and horizontal modes. In this study, we aimed to investigate the LC-OCT morphological features of a series of eyelid skin lesions, correlating them to histopathological findings. METHODS: Patients with biopsy-proven equivocal skin lesion in the eyelid area, previously investigated by means of LC-OCT, were included in the study. Percentage overall agreement was estimated for LC-OCT and histopathological diagnosis for study cases. RESULTS: A total of 51 patients (28 women, 23 men; mean age 66.4 years old), for a total of 51 skin lesions, were assessed. The histopathological diagnosis consisted of 30 malignant and 21 benign tumors. Different entities were characterized by peculiar findings in LC-OCT, alike to histopathological features, allowing for an accurate "in vivo" classification in almost all cases, with a diagnostic concordance with histopathology of 92.1% (47/51). CONCLUSIONS: By integrating this new imaging technique into the assessment of suspicious tumors in this area, diagnostic accuracy may increase, improving strategies adopted in multidisciplinary meetings and patient-centered care.

Orbital Exenteration in Recurrence Cancer: 5 Years Experience.

INTRODUCTION: The purpose of this study was to assess the overall survival (OS) and disease-free survival (DFS) of patients who underwent orbital exenteration for periorbital, conjunctival, and primary intraorbital carcinomas. Additionally, we assessed the outcomes of anterior retrograde temporalis muscle flap restoration. METHODS: For all patients who had orbital exenteration in the previous five years, a non-comparative retrospective assessment of their medical records, histology, and radiographic imaging was carried out. We investigated the relationships between the various qualitative factors using Cramer's V Kaplan-Meier (KM) analysis. For each of the patient's categorical factors that were of relevance, estimates of the survival distribution were displayed, and log-rank tests were used to determine whether the survival distributions were equal. RESULTS: This study looks at 19 participants. The sample is made up of 13 men (68%) and 6 women (32%). The degree of relationship (Cramer's V index) between lymph node metastases (N) and the existence of distant metastases (M) is high, at 64%, and is statistically significant because the p-value is 0.0034 < 0.005. Lymph node metastases had a statistically significant impact on overall survival (p = 0.04 < 0.05). Thirteen of the nineteen patients tested had no palsy (68%). There was no one presenting a CSF leak. CONCLUSION: Our findings show how crucial it is to identify any lymph node involvement that orbital neoplasms may have. In patients who have received many treatments, sentinel lymph node biopsy (SLNB) may be used to determine the stage and spread of the cancer. To determine whether additional tumor characteristics may be explored, more expertise in the SLNB field for patients with orbital cancer who have received many treatments may be helpful. To prevent additional scarring and to be comparable to previous techniques for facial nerve lesions, the anterior retrograde approach and the transorbital procedure for temporal muscle flap in-setting are both effective methods.

Maximal Fusion Capacity and Efficient Replenishment of the Dense Core Vesicle Pool in Hippocampal Neurons.

Neuropeptides and neurotrophins, stored in dense core vesicles (DCVs), are together the largest currently known group of chemical signals in the brain. Exocytosis of DCVs requires high-frequency or patterned stimulation, but the determinants to reach maximal fusion capacity and for efficient replenishment of released DCVs are unknown. Here, we systematically studied fusion of DCV with single vesicle resolution on different stimulation patterns in mammalian CNS neurons. We show that tetanic stimulation trains of 50-Hz action potential (AP) bursts maximized DCV fusion, with significantly fewer fusion event during later bursts of the train. This difference was omitted by introduction of interburst intervals but did not increase total DCV fusion. Interburst intervals as short as 5 s were sufficient to restore the fusion capacity. Theta burst stimulation (TBS) triggered less DCV fusion than tetanic stimulation, but a similar fusion efficiency per AP. Prepulse stimulation did not alter this. However, low-frequency stimulation (4 Hz) intermitted with fast ripple stimulation (200 APs at 200 Hz) produced substantial DCV fusion, albeit not as much as tetanic stimulation. Finally, individual fusion events had longer durations with more intense stimulation. These data indicate that trains of 50-Hz AP stimulation patterns triggered DCV exocytosis most efficiently and more intense stimulation promotes longer DCV fusion pore openings.SIGNIFICANCE STATEMENT Neuropeptides and neurotrophins modulate multiple regulatory functions of human body like reproduction, food intake or mood. They are packed into dense core vesicles (DCVs) that undergo calcium and action potential (AP) fusion with the plasma membrane. In order to study the fusion of DCVs in vitro, techniques like perfusion with buffer containing high concentration of potassium or electric field stimulation are needed to trigger the exocytosis of DCVs. Here, we studied the relationship between DCVs fusion properties and different electric field stimulation patterns. We used six different stimulation patterns and showed that trains of 50-Hz action potential bursts triggered DCV exocytosis most efficiently and more intense stimulation promotes longer DCV fusion pore openings.

The Use of a CAD/CAM Thermoformed Splints System in Closed Reduction of Condylar Fractures.

(1) Background: Mandibular fractures are very common. Common indications of closed treatment for mandibular fractures are non-displaced or minimally displaced simple fractures in adult compliant patients with good dentition, the absence of occlusal disruption, and fractures in growing children. In closed treatment, the mandible is maintained in centric occlusion with a maxillomandibular fixation (MMF) with orthodontic elastics. Many methods of MMF have been described, often using orthodontic appliances. In recent years, CAD-CAM technology has improved many procedures used in maxillofacial surgery and orthodontics. The device we present is manufactured following a digital workflow, and was designed specifically for MMF. (2) Materials: Two patients with mandibular fractures were treated with an MMF method whose procedure comprised scanning of the dental arches, followed by construction of thermoformed splints on which buttons for the elastics and retention holes are made. The splints were fixed on the dental arches with composite resin at the level of the holes, and were kept in place for the period of healing of the fracture, with the intermaxillary elastics hooked to the buttons. (3) Results: The application time of the splints was very quick. The splints remained stable for the necessary time, without causing particular discomfort to the patients. (4) Conclusions: From our experience, this technique has proved to be reliable and reproducible and could represent a valid tool in the closed treatment of mandibular fractures.

[Acute Kidney Injury Caused by Orellanic Syndrome: Case Report].

Orellanic syndrome is caused by fungi of the Cortinarius orellanus and speciosissimus (Europe) species, Cortinarius fluorescens (South America), and Cortinarius rainierensis (North America). Orellanic syndrome is characterized by initially nonspecific symptoms such as muscle and abdominal pain, and a metallic taste sensation in the mouth. After a few days, more specific symptoms appear, such as intense thirst, headache, chills without fever, and anorexia, followed by a phase of polyuria and then of oligoanuria. Renal failure occurs in 70% of cases and is often irreversible. The clinical case involves a 52-year-old man who developed acute renal failure from Orellanic syndrome, necessitating hemodialysis.

Patient-Specific Facial Implants in Polyetheretherketone and Their Stability: A Preliminary Study.

BACKGROUND: Polyetheretherketone (PEEK) is a synthetic material with many favorable characteristics; PEEK implants are increasingly used for a variety of applications ranging from cranioplasty to orthopedic surgery and facial implants. METHODS: This study is a retrospective review of patients who underwent PEEK implant placement in our department over the last 5 years. Polyetheretherketone computer-aided design and manufacture facial implants were designed from high-resolution computed tomography (CT) scans of each patient. The implants placed were onlay implants used for facial rehabilitation purposes to correct malformative and posttraumatic malformations. RESULTS: Twenty-eight consecutive patients (11 males and 17 females) underwent PEEK implant positioning between January 2015 and December 2020. Common indications were anterior plagiocephaly, hemifacial microsomia, and residual facial imbalance after orthognathic surgery. No complications of implant breakdown, exposure, infection, or displacement were noticed during the follow-up period. During routine controls on 3 patients, we requested a craniomaxillofacial CT scan for reasons unrelated to the implanted prostheses. The CT scans were all high resolution (<1-mm slices). The CT images indicated that bone was starting to form around the implant in all 3 patients as well as in the penetrating holes that were planned in the implants. CONCLUSIONS: In our experience, computer-designed, patient-specific PEEK onlay implants are a valid option for the treatment of malformative and posttraumatic malformations. This is, to the best of our knowledge, the first clinical report on bone reaction to PEEK implantation in the maxillofacial field. Moreover, based on the signs of bone regrowth that we observed in CT controls we can presume that the design of this type of prosthesis can probably take advantage of some technical stratagems not yet codified and fully exploited. Despite our preliminary favorable results, further multicentric and comparative studies are necessary to evaluate outcomes and better understand the behavior of this promising material and thus optimize its use in craniomaxillofacial surgery.

Agrimonia: a dataset on livestock, meteorology and air quality in the Lombardy region, Italy.

The air in the Lombardy region, Italy, is one of the most polluted in Europe because of limited air circulation and high emission levels. There is a large scientific consensus that the agricultural sector has a significant impact on air quality. To support studies quantifying the role of the agricultural and livestock sectors on the Lombardy air quality, this paper presents a harmonised dataset containing daily values of air quality, weather, emissions, livestock, and land and soil use in the years 2016-2021, for the Lombardy region. The daily scale is obtained by averaging hourly data and interpolating other variables. In fact, the pollutant data come from the European Environmental Agency and the Lombardy Regional Environment Protection Agency, weather and emissions data from the European Copernicus programme, livestock data from the Italian zootechnical registry, and land and soil use data from the CORINE Land Cover project. The resulting dataset is designed to be used as is by those using air quality data for research.

Multidisciplinary ocular and periocular cancers meetings: implementation in a tertiary referral center and analysis over a 12-months period.

PURPOSE: The complexity of multimodal approaches in cancer management has lately led to the establishment of multidisciplinary tumor boards (MDTBs) to define targeted, patient-centered treatment strategies. However, few data are available regarding the application of this approach in Ocular Oncology. Hereby, the Authors analyze the implementation and outcomes of a trained MDTB in a tertiary ocular oncology referral center. METHODS: A retrospective descriptive analysis of MDTB meetings discussing patients with ocular and periocular cancers, over a 12-months period, was carried out. Data were grouped by main site involved, topics discussed and final clinical decisions therefore taken. Meetings were held by a constant 'Core team' or - when required - by a broader 'Extended team'. RESULTS: During the observational period 86 cases were discussed. In 27 patients ocular surface tissues were involved (31%), in 25 patients orbital tissues (29%), in 22 patients eyelids (26%), and in 12 patients intraocular tissues (14%). In 13 cases (15%) naïve or referred new patients, in 34 cases (40%) imaging or histopathologic reports and in 39 cases (45%) treatment plans were discussed. Regarding final decisions, a treatment plan was scheduled in 47 cases (55%) and a diagnostic ascertainment was required in 27 patients (31%); locally advanced and/or systemic diseases were referred or teamed up with other specialists in 12 cases (14%). CONCLUSIONS: Ocular Oncology multidisciplinary team, by sharing expertise of different specialists, ensures a comprehensive evaluation of patients improving the accuracy of diagnosis and staging upon which planning a proper treatment. Further studies are needed to assess if this approach may also improve the outcomes and prognosis of patients.

Our problems and observations in 3D facial implant planning.

BACKGROUND: Three-dimensional renderings of two-dimensional computed tomography data have allowed for more precise analysis in the craniofacial field. Design, engineering, architecture, and other industries have paved the way for the manipulation and printing of three-dimensional objects. The usual planning is only carried out based on the bony structures, often without taking into consideration the presence of soft tissues and soft structures. During our practice, we have found ourselves facing the challenge posed by these structures; the aim of this article is to discuss our experience in designing implants presenting our tips and tricks for a better planning leading to an easy and reliable positioning. CASE PRESENTATION: We have retrieved all patients in 5 years among those who underwent computer-aided design/computer-aided manufacturing implant placement in the last 5 years in order to review the eventual problems and the solutions found. A total number of 25 patients were retrieved and, among them, 10 patients were selected, in which planning inaccuracy caused difficulties during implant placement and which then led to induced changes during the planning of similar cases or in which the problems were noted before or during the planning which led to changes in the plan to address those problems. Six of the selected cases were polyetheretherketone facial implants for the correction of residual deformities in malformed or deformed patients. One case was a delayed orbital reconstruction with a titanium implant. Two cases were titanium functional and anatomical reconstruction of the mandible in patients with failed post-oncological reconstructions. There was 1 case with a mandibular ramus complex and hard-to-treat fracture. CONCLUSIONS: The planning of the implant mostly relies on hard tissue three-dimensional reconstruction, but it should not be limited at what is immediately evident. A surgeon's clinical experience should always guide the process, with knowledge of the patient's anatomy and evaluation of the quality and of the soft tissue response being taken into consideration. The implant should always be tailored not only based on the bone defect and evaluations but also using the patient's previewed and actual anatomy, evaluating eventual interferences and pitfalls.

Reduced dynamin-1 levels in neurons lacking MUNC18-1.

MUNC18-1 (also known as syntaxin-binding protein-1, encoded by Stxbp1) binds to syntaxin-1. Together, these proteins regulate synaptic vesicle exocytosis and have a separate role in neuronal viability. In Stxbp1 null mutant neurons, syntaxin-1 protein levels are reduced by 70%. Here, we show that dynamin-1 protein levels are reduced at least to the same extent, and transcript levels of Dnm1 (which encodes dynamin-1) are reduced by 50% in Stxbp1 null mutant brain. Several, but not all, other endocytic proteins were also found to be reduced, but to a lesser extent. The reduced dynamin-1 expression was not observed in SNAP25 null mutants or in double-null mutants of MUNC13-1 and -2 (also known as Unc13a and Unc13b, respectively), in which synaptic vesicle exocytosis is also blocked. Co-immunoprecipitation experiments demonstrated that dynamin-1 and MUNC18-1 do not bind directly. Furthermore, MUNC18-1 levels were unaltered in neurons lacking all three dynamin paralogues. Finally, overexpression of dynamin-1 was not sufficient to rescue neuronal viability in Stxbp1 null mutant neurons; thus, the reduction in dynamin-1 is not the single cause of neurodegeneration of these neurons. The reduction in levels of dynamin-1 protein and mRNA, as well as of other endocytosis proteins, in Stxbp1 null mutant neurons suggests that MUNC18-1 directly or indirectly controls expression of other presynaptic genes.

Clinical Evaluation of the Optical Filter for Autofluorescence Glasses for Oral Cancer Curing Light Exposed (GOCCLES®) in the Management of Potentially Premalignant Disorders: A Retrospective Study.

BACKGROUND: Any oral potentially malignant disorders (OPMDs) must be regularly monitored through clinical examination to detect any possible malignant transformation. Conventional intraoral exams, however, can be difficult because these conditions may resemble benign lesions. For this reason, several non-invasive diagnostic technologies have been developed to help the clinician in detecting and distinguishing between cancerous and benign lesions. Epithelial dysplasia can be considered the most important predictor of malignant evolution. Therefore, in this study we aim to evaluate the ability of an optical filter for autofluorescence Glasses for Oral Cancer Curing Light Exposed (GOCCLES®) and of toluidine blue staining in identifying dysplastic areas in patients with OPMDs. METHODS: In this retrospective study, medical records, photographs and videos of 25 patients with oral lesions were analyzed. Forty-two biopsy samples in 25 patients with OPMDs and at least one suspicious oral mucosa lesion that were evaluated in white light, autofluorescence with optical filter GOCCLES®, toluidine blue staining and then biopsied with histopathological analysis were analyzed. RESULTS: The sensitivity and specificity for the autofluorescence evaluation with GOCCLES® for identifying dysplasia or carcinoma were 66% and 48%, respectively. The positive and negative predictive values were 34% and 77%, respectively, and the accuracy was 53%. The sensitivity and specificity for toluidine blue staining were 91% and 68%, respectively. The positive and negative predictive values were 55% and 95%, respectively, and the accuracy was 75%. CONCLUSIONS: The optical filter for autofluorescence (GOCCLES®) and toluidine blue staining are simple, inexpensive, rapid and non-invasive procedures that can assist the clinician in distinguishing OPMDs from healthy mucosa but they are not able to distinguish benign and malignant lesions.

Influence of SARS-CoV-2 lockdown on the incidence of facial trauma in a tertiary care hospital in Rome, Italy.

BACKGROUND: Italy has been the first affected country in the western hemisphere by SARS-CoV-2 with over 200,000 cases during the first months of the pandemics. To control the spread of the virus, the whole country was placed under lockdown with limitations in the circulation of people and vehicles from March 2020 to the first half of the month of May. METHODS: We aimed to analyze the incidence and type of facial traumas referred to our tertiary care hospital during the months of Italy lockdown due to SARS-CoV-2 spread compared with those during the same months of 2019 to determine eventual variations in the incidence, type and causes of trauma. RESULTS: During the 2 months of COVID-19-related lockdown, a dramatic decrease in facial trauma patients was observed at our tertiary care hospital with a shift toward older age ranges. Regarding the causes of trauma, the largest percentage reduction was found in road, sports and work accidents; this percentage reduction was not found in aggressions. CONCLUSIONS: A small increase in the percentage was also found regarding surgical indications, likely because more severe cases were more prone to be referred to the hospital despite the fear of being infected.

An Orthodontic Index assessment and its relationship with total treatment time in surgery first orthognathic approach: an observational study.

BACKGROUND: The aim of this study was to highlight the connection between orthodontic difficulty before surgical treatment and in the transient malocclusion as evaluated by the mean of the of Complexity, Outcome, and Need (ICON) Score and total treatment time in surgery-first approach (SFA). METHODS: For each patient, the ICON Score was evaluated preoperatively and on the 3rd postoperative day in order to assess the orthodontic difficulty of presurgical occlusion and the transient malocclusion. RESULTS: Our group of patients at the preoperative stage showed score values between hard and very hard with only one patient scored as "easy" and nine "medium" patients. All scores lowered after surgical treatment. This confirms that the surgery first approach can change a malocclusion from not orthodontically treatable to an orthodontically treatable one. In our study, this was objectified by improvements in the ICON Score. CONCLUSIONS: In the conventional three-phase approach of orthognathic surgery the total treatment time found in literature is around 18-36 months. In our study, even the most difficult cases do not have a duration of more than 15 months This demonstrates that the surgery-first approach can reduce the total treatment time even in more severe cases.

Patient First: Surgery First and More.

INTRODUCTION: The success of surgery first approach has been defined by the number of advantages offered and is definitively determined by the satisfaction of the patients themselves. The strength of this protocol resides in its philosophy that puts the patient at the center of the whole diagnostic-therapeutic process. The compliance of the patient, its happiness and comfort are the best guarantee of a good final results. While pursuing this philosophy we have wondered whether there was way to increase the comfort of surgery first approach even more and to make it even more appealing for the patients. For these reasons, we have decided to work on a preliminary protocol in order to reduce or even eliminate the use of orthodontic braces and wires during perioperative stages. Materials and Methods: No orthodontic braces or wires are bonded on the teeth before surgery. Intraoperatory intermaxillary fixation (IMF) is carried out with the use of IMF screws which are positioned at the beginning of the operation on the edge between keratinized and nonkeratinized gingiva. Once the osteotomies are performed IMF with IMF screws is carried out on the planned occlusion with the use of surgical splints.Discussion and Conclusions: In selected cases the postsurgical orthodontic treatment can be carried out with the use of clear aligners, completely eliminating the need of braces and wires with an additional level of comfort.

Approach to Fronto-Orbital Sequelae in Anterior Synostotic Plagiocephaly: Our Flow Chart Based on Di Rocco Classification.

INTRODUCTION: Anterior synostotic plagiocephaly recognizes the synostosis of one of the hemicoronal sutures as a cause and can manifest itself with varying degrees of severity. Clinically it presents a reduction of the sagittal growth of the affected side and flattening of the frontoparietal complex. MATERIALS AND METHODS: The authors retrospectively examined our case sample dividing it into 3 groups based on the Di Rocco classification. For each category, we assessed the extent of facial alterations at the end of skeletal growth and retrospectively analyzed the surgical options aimed at correcting aesthetic and skeletal deficits. RESULTS: The authors found that predictable results could be obtained by standardizing the surgical procedure based on Di Rocco's classification groups; in particular, the authors achieved satisfactory results by assigning a specific surgical procedure to each class.

Dynamin controls neuropeptide secretion by organizing dense-core vesicle fusion sites.

Synaptic vesicles (SVs) release neurotransmitters at specialized active zones, but release sites and organizing principles for the other major secretory pathway, neuropeptide/neuromodulator release from dense-core vesicles (DCVs), remain elusive. We identify dynamins, yeast Vps1 orthologs, as DCV fusion site organizers in mammalian neurons. Genetic or pharmacological inactivation of all three dynamins strongly impaired DCV exocytosis, while SV exocytosis remained unaffected. Wild-type dynamin restored normal exocytosis but not guanosine triphosphatase-deficient or membrane-binding mutants that cause neurodevelopmental syndromes. During prolonged stimulation, repeated use of the same DCV fusion location was impaired in dynamin 1-3 triple knockout neurons. The syntaxin-1 staining efficiency, but not its expression level, was reduced. αSNAP (α-soluble N-ethylmaleimide-sensitive factor attachment protein) expression restored this. We conclude that mammalian dynamins organize DCV fusion sites, downstream of αSNAP, by regulating the equilibrium between fusogenic and non-fusogenic syntaxin-1 promoting its availability for SNARE (SNAP receptor) complex formation and DCV exocytosis.

Functional Upper Airway Space Endoscopy: A Prognostic Indicator in Obstructive Sleep Apnea Treatment with Mandibular Advancement Devices.

PURPOSE: The use of a mandibular advancement device (MAD) in the treatment of obstructive sleep apnea (OSA) is a consolidated therapy. This study aimed to evaluate the predictive value of awake upper airways (UA) functional endoscopy in identifying the outcome of MAD therapy. METHODS: This observational prospective study included 30 adult OSA patients, all patients underwent pre-treatment awake UA functional endoscopy, during the exam subjects were instructed to advance their mandible maximally, and they were divided into three different groups according to the response of the soft tissue, group A (expansion), group B (stretch), group C (unchanged). The results of this test were used in combination with other noninvasive indexes to predict the treatment outcome in terms of apnea-hypopnea index (AHI) reduction. RESULTS: We found that a substantial AHI reduction occurred in group A and group B while e slight AHI reduction was measured in group C. CONCLUSION: Based on our experience the awake UA endoscopy is a valid prognostic exam for discriminating responder and non-responder patients; in addition our results indicate the possibility of predicting a range of post-treatment AHI index values.

Quantitative analysis of dense-core vesicle fusion in rodent CNS neurons.

Neuropeptides are essential signaling molecules secreted by dense-core vesicles (DCVs). They contribute to information processing in the brain, controlling a variety of physiological conditions. Defective neuropeptide signaling is implicated in several psychiatric disorders. Here, we provide a protocol for the quantitative analysis of DCV fusion events in rodent neurons using pH-sensitive DCV fusion probes and custom-written analysis algorithms. This method can be used to study DCV fusion mechanisms and is easily adapted to investigate fusion principles of other secretory organelles. For complete details on the use and execution of this protocol, please refer to Persoon et al. (2019).

Image Captioning Using Motion-CNN with Object Detection.

Automatic image captioning has many important applications, such as the depiction of visual contents for visually impaired people or the indexing of images on the internet. Recently, deep learning-based image captioning models have been researched extensively. For caption generation, they learn the relation between image features and words included in the captions. However, image features might not be relevant for certain words such as verbs. Therefore, our earlier reported method included the use of motion features along with image features for generating captions including verbs. However, all the motion features were used. Since not all motion features contributed positively to the captioning process, unnecessary motion features decreased the captioning accuracy. As described herein, we use experiments with motion features for thorough analysis of the reasons for the decline in accuracy. We propose a novel, end-to-end trainable method for image caption generation that alleviates the decreased accuracy of caption generation. Our proposed model was evaluated using three datasets: MSR-VTT2016-Image, MSCOCO, and several copyright-free images. Results demonstrate that our proposed method improves caption generation performance.