Synaptophysin is a selective marker for axons in human cutaneous end organ complexes.

BACKGROUND: Small clear synaptic-like vesicles fill axon terminals of mechanoreceptors. Their functional significance is controversial and probably includes release of neurotransmitters from afferent axon terminals. Synaptophysin, a major protein of the synaptic vesicle membrane, is present in presynaptic endings of the central and peripheral nervous systems. It is also expressed in mechanosensory neurons which extend into skin forming sensory corpuscles. Nevertheless, synaptophysin occurrence in these structures has never been investigated. METHODS: Here we used immunohistochemistry to detect synaptophysin in adult human dorsal root ganglia, cutaneous Meissner and Pacinian corpuscles and Merkel cell-neurite complexes from foetal to elderly period. Moreover, we analyzed whether synaptophysin co-localizes with the mechano-gated protein PIEZO2. RESULTS: Synaptophysin immunoreactivity was observed in primary sensory neurons (36 ± 6%) covering the entire soma size ranges. Axons of Meissner's and Pacinian corpuscles were positive for synaptophysin from 36 and 12 weeks of estimated gestational age respectively, to 72 years old. Synaptophysin was also detected in Merkel cells (from 14 weeks of estimated gestational age to old age). Additionally in adult skin, synaptophysin and PIEZO2 co-localized in the axon of Meissner and Pacinian corpuscles, Merkel cells as well as in some axons of Merkel cell-neurite complexes. CONCLUSION: Present results demonstrate that a subpopulation of primary sensory neurons and their axon terminals forming cutaneous sensory corpuscles contain synaptophysin, a typical presynaptic vesicle protein. Although the functional relevance of these findings is unknown it might be related to neurotransmission mechanisms linked to mechanotransduction.

In Vitro Development of a New Sponge-Based Delivery System for Intracanal Antimicrobial Administration in Endodontic Treatment.

This study aimed to evaluate the in vitro performance of collagen-based sponges as a drug delivery system for intracanal antimicrobial administration. Four groups of loaded collagen-based sponges (A, 0.3% w/v amoxicillin trihydrate: potassium clavulanate (4:1); B, 0.03% w/v chlorhexidine gluconate [CHX]; C, 0.3% w/v amoxicillin trihydrate: potassium clavulanate (4:1) and 0.03% w/v CHX; D, 1% w/v amoxicillin trihydrate: potassium clavulanate (4:1) and 0.03% w/v CHX) were designed. Release kinetics were tested in vitro on cultures in Petri dishes, and the effect on bacterial biofilms was studied ex vivo on 114 extracted human single-rooted teeth. Biofilm formation was tested by scanning electron microscopy (SEM). Collagen sponges containing amoxicillin and chlorhexidine showed a time-sustained antimicrobial effect in vitro and were also able to destroy mature biofilms ex vivo. This datum was validated by means of SEM-based study of E. faecalis and S. aureus biofilms.

A Case Report of Malignant Eccrine Porocarcinoma Involving the Palm Requiring Surgical Excision and Free Flap Reconstruction.

BACKGROUND Eccrine porocarcinoma (EPC) was first described in 1963 as an epidermotropic eccrine carcinoma. Fifty years later, its etiology remains poorly understood. The infrequent nature of this disease merits further inquiry into its etiology, presentation, and standards of management. Furthermore, the propensity for metastasis, which may be as high as 31% on presentation, increases the importance of investigating this rare disease. CASE REPORT The patient was a 63-year-old mechanic who presented with the lesion as a chronic wound following a chemical exposure. The lesion involved the ulnar aspect of his right palm and had concern for extension to the underlying tendons. He underwent a wide excision extending from the wrist to the proximal interphalangeal joint, preserving the ulnar neurovascular bundle. The hand was reconstructed with an anterolateral thigh fascia perforator flap and a skin graft. He had an excellent functional and cosmetic recovery. Unfortunately, he developed metastases to the lymph nodes, necessitating an axillary lymphadenectomy followed by adjuvant chemoradiation using concurrent cisplatin and docetaxel with radiation for 6 weeks. Follow-up at 18 months found no recurrence. CONCLUSIONS Cases of EPC presenting in the fingers have been managed with amputation of the involved phalanges; however, in addition to obtaining complete excision with negative margins, surgeons who deal with tumors of the hand must also consider the goals of limb preservation, functional preservation, and functional reconstruction. Options for reconstruction following excision include primary closure, dermal regeneration templates, skin grafts, flaps, and free-tissue transfer, depending on what tissue types are needed.

Functional Outcomes Regarding Facial Artery Musculomucosal Flap for Reconstruction of Partial Glossectomy Defects.

BACKGROUND: The surgical management and reconstruction after ablation of squamous cell carcinoma of the oral tongue and floor of mouth are quite challenging. If not reconstructed properly, the deficits resulting from the extirpation of even relatively small (T1 and T2) tumors of the tongue can impact speech and deglutition via tongue tethering and poor anterolateral mobility. Functional outcome studies regarding the utility of the pedicled facial artery musculamucosal (FAMM) flap for reconstruction of partial glossectomy defects are limited. METHODS: This is a retrospective single institutional study of patients who underwent FAMM flap reconstruction for oral cavity defects resulting from partial glossectomy (2009-2013). Follow-up data included postoperative complications, defect size, operative time, and subjective functional results (tongue mobility, speech, and swallowing capabilities).The MD Anderson Dysphagia Inventory and a limited self-assessment of speech were sent to all living patients in this initial tongue cancer cohort to assess aspects of functional status. RESULTS: Of the 21 patients studied in this initial FAMM flap cohort, 18 are currently living. The MD Anderson Dysphagia Inventory and a limited self-assessment survey of speech were sent to these individuals 6 months after treatment completion. Eight patients (44%) returned completed questionnaires. All of the respondents disagreed or strongly disagreed with the statement that they felt excluded from others because of their eating habits, 6 of the 8 of the respondents stated that they disagreed or strongly disagreed with the statement that they have to limit their food intake, and none felt that others were irritated by their eating habits. All felt that their speech was either good, very good, or excellent. No surveyed patient reported having job difficulty because of their speech. CONCLUSIONS: The FAMM flap is a reliable alternative for reconstruction of small oral tongue defects without functional deficits and a great alternative to free flap reconstruction of medium-sized defects. The encouragement of patient functional outcome studies and longitudinal follow-up studies need to be conducted in efforts to best tailor a reconstruction plan for patients with oral tongue cancers.

Entrapment Neuropathy Causing Persistent Headache Symptoms after Nonsurgical Rhinoplasty.

The frequency of nonsurgical rhinoplasty has increased in recent years. The occurrence of headaches or migraine symptoms, and their treatment following nonsurgical rhinoplasty, have been scarcely described in the literature. Here, we present a patient who presented with subjective complaints of a new onset headache immediately after nonsurgical rhinoplasty, with subsequent reversal of her symptoms using hylauronidase. Furthermore, a literature review was conducted to establish a possible anatomical pathophysiologic mechanism of these symptoms seen in this patient. METHODS: A case report of a patient who developed persistent headache symptoms after nonsurgical rhinoplasty, with reversal of symptoms using hylaronidase, is described. A literature review of studies on patients developing headaches or migraine-like symptoms after nonsurgical rhinoplasty was conducted, along with a review of the anatomic causes of migraines. RESULTS: Of the 147 relevant citations identified in our search, only 1 individual case report describes a patient who developed a migraine headache after undergoing a nonsurgical rhinoplasty via an injection of hyaluronic acid filler. This was promptly resolved with the utilization of a hyaluronidase injection. The majority of the relevant articles in our search focused on the alarming and most feared complication of vascular compromise of the nasal tissue and intravascular embolization. Within the literature, there was no case series of nonsurgical-rhinoplasty-induced migraines taking into account our inclusion criteria. CONCLUSIONS: This article demonstrates the paucity of literature regarding nonsurgical-rhinoplasty-induced headaches. Although a causation effect cannot be linked, our study highlights a rare phenomenon associated with this ever-increasing aesthetic procedure.

An update on X-Linked agammaglobulinaemia: clinical manifestations and management.

PURPOSE OF REVIEW: X-linked agammaglobulinaemia (XLA) is a congenital defect of development of B lymphocytes leading to agammaglobulinaemia. It was one of the first primary immunodeficiencies described, but treatment has remained relatively unchanged over the last 60 years. This summary aims to outline the current outcomes, treatments and future research areas for XLA. RECENT FINDINGS: Immunoglobulin therapy lacks IgA and IgM, placing patients at theoretical risk of experiencing recurrent respiratory tract infections and developing bronchiectasis despite best current therapy. Recent cohort studies from Italy and the USA conform that bronchiectasis remains a major burden for this group despite best current efforts. However, gene therapy offers a potential cure for these patients with proven proof of concept murine models. SUMMARY: The potential limitations of current immunoglobulin therapy appear to be confirmed by recent cohort studies, and therefore further work in the development of gene therapy is warranted. Until this is available, clinicians should strive to reduce the diagnostic delay, regularly monitor for lung disease and individualize target immunoglobulin doses to reduce infection rates for their patients.

Re-excision Rate after Partial Mastectomy in Oncoplastic Breast-Conserving Surgery: A Single-Institutional Experience and Review of the Literature.

BACKGROUND: Applying oncoplastic techniques to breast conservation therapy is believed to improve cosmetic and oncologic outcomes, compared with standard breast conservation therapy alone. This study aimed to perform a comprehensive review of the literature comparing outcomes of oncoplastic breast conservation therapy (BCT + R) with that of standard breast conservation therapy alone (BCT). A secondary objective was to compare these results to outcomes after oncoplastic breast conservation therapy performed at our institution (BCT + r). METHODS: A literature search was performed in PubMed using key words, "oncoplastic," "partial breast reconstruction," and "breast conservation therapy." Case reports, case series, and studies with fewer than 10 patients and studies that did not report re-excision rates were excluded. A retrospective chart review was performed from 2011 to 2017 of all cases of oncoplastic breast conservation therapy performed at our institution by a single 2-surgeon team consisting of 1 breast surgeon and 1 plastic surgeon. Outcomes were assessed by comparing re-excision rates between the 3 comparison groups (BCT, BCT + R, BCT + r). RESULTS: The BCT group was made of 5965 patients (22 articles), and the BCT + R group comprised 2564 patients (41 articles). Re-excision rates in the BCT + R group were lower (4.0%) than the BCT group (17.2%, P = 0.0001). One hundred seventy-two patients comprised the BCT + r group and underwent oncoplastic breast conservation therapy during the study period at our institution. The re-excision rate in the BCT + r group was 1.7% and was significantly lower than the BCT group (P = 0.0001) and lower but not significantly different from the BCT + R group (P = 0.2113). CONCLUSIONS: Oncoplastic breast conservation therapy leads to lower re-excision rates compared with standard breast conservation therapy. Oncoplastic breast conservation therapy may improve oncologic outcomes compared with standard breast conservation therapy by allowing for more extensive resection without compromising aesthetic results.

Buccal Fat Pad Excision: Proceed with Caution.

BACKGROUND: Buccal fat pad excision is offered as a means of obtaining a more aesthetic midface. This procedure has been documented in the form of countless videos on Instagram and other social media platforms with no long-term patient follow-up. We performed a retrospective analysis of published data regarding buccal fat pad excision and sought to better elucidate pitfalls regarding this underreported procedure. METHODS: A literature search was conducted in October 2017 through the PUBMED database regarding the utility of buccal fat pad excision in the setting of aesthetic improvement of the midface. Reference articles were screened to obtain relevant studies. A total of 121 citations were identified in the search but after eliminating duplicate studies and abstracts and utilizing predefined inclusion/exclusion criteria only 11 articles were satisfactory. None of these articles demonstrated any long-term patient follow-up. RESULTS: Out of the 121 relevant citations identified, only 2 studies published describe a case series of > 5 patients regarding cheek or midface sculpturing with buccal fat pad excision for aesthetic purposes, the total sample size between these 2 studies was 53 patients. Neither of the studies had follow-up regarding patient satisfaction or related outcomes. CONCLUSIONS: Buccal fat pad resection as an aesthetic improvement of the midface has been described, but follow-up regarding loss of subcutaneous fat with aging and late secondary deformities have not been published in the literature. Further research in long-term patient follow-up including patient satisfaction and the encouragement of reporting postoperative complications is warranted.

Phosphorylation of the neurogenic transcription factor SOX11 on serine 133 modulates neuronal morphogenesis.

The intellectual disability gene, Sox11, encodes for a critical neurodevelopmental transcription factor with functions in precursor survival, neuronal fate determination, migration and morphogenesis. The mechanisms regulating SOX11's activity remain largely unknown. Mass spectrometric analysis uncovered that SOX11 can be post-translationally modified by phosphorylation. Here, we report that phosphorylatable serines surrounding the high-mobility group box modulate SOX11's transcriptional activity. Through Mass Spectrometry (MS), co-immunoprecipitation assays and in vitro phosphorylation assays followed by MS we verified that protein kinase A (PKA) interacts with SOX11 and phosphorylates it on S133. In vivo replacement of SoxC factors in developing adult-generated hippocampal neurons with SOX11 S133 phospho-mutants indicated that phosphorylation on S133 modulates dendrite development of adult-born dentate granule neurons, while reporter assays suggested that S133 phosphorylation fine-tunes the activation of select target genes. These data provide novel insight into the control of the critical neurodevelopmental regulator SOX11 and imply SOX11 as a mediator of PKA-regulated neuronal development.

Phosphorylation Modulates the Subcellular Localization of SOX11.

SOX11 is a key Transcription Factor (TF) in the regulation of embryonic and adult neurogenesis, whose mutation has recently been linked to an intellectual disability syndrome in humans. SOX11's transient activity during neurogenesis is critical to ensure the precise execution of the neurogenic program. Here, we report that SOX11 displays differential subcellular localizations during the course of neurogenesis. Western-Blot analysis of embryonic mouse brain lysates indicated that SOX11 is post-translationally modified by phosphorylation. Using Mass Spectrometry, we found 10 serine residues in the SOX11 protein that are putatively phosphorylated. Systematic analysis of phospho-mutant SOX11 resulted in the identification of the S30 residue, whose phosphorylation promotes nuclear over cytoplasmic localization of SOX11. Collectively, these findings uncover phosphorylation as a novel layer of regulation of the intellectual disability gene Sox11.

Prevalence of Premolars with Dens Evaginatus in a Taiwanese and Spanish Population and Related Complications of the Fracture of its Tubercle.

OBJECTIVE: Dens evaginatus (DE) is an odontogenic developmental anomaly that can be defined as a supernumerary tubercle structure that extends from the occlusal surface of the affected tooth. Tubercular fracture or attrition of the tubercle, invaded by pulp tissue, may cause various pulpal diseases, such as pulpitis, pulp necrosis, and periapical periodontitis. This study aimed to determine the prevalence of premolars with DE in Taiwanese and Spanish study populations and to report associated dental complications. METHODS: This study was based on the clinical examination of volunteers of Spanish and Taiwanese origin, recruited among the undergraduate dentistry students at CEU-Cardenal Herrera University, Valencia, Spain. Informed consents were obtained from students identified with DE. Additional examinations were performed, including vitality test, percussion, palpation, and radiographs, to diagnosis the status of the pulp and periapical tissue. RESULTS: The prevalence of DE among Taiwanese students was 4.08%, compared to 0% in the Spanish Caucasian group. In the Taiwanese group, the occurrence of DE in premolars was more common in the mandibular (78.9%) compared to the maxillar region (21.1%). In 84% of the cases, DE-affected teeth were found bilaterally. The mandibular second premolar was the most commonly involved tooth (57.8%). When investigating the complications related to DE among six affected Taiwanese students, it was found that two teeth (10.5%) had received pulp treatment, one of them prior to complete root formation. CONCLUSION: DE appears to be more prevalent in people of Mongoloid origin and rare in those of Caucasian origin. The wear or fracture of DE may affect pulpal tissue, leading to incomplete root growth.

Congenital pleural effusions: 15 years single-centre experience from North-East England.

AIM: The aim of this study is to add to the scant literature on congenital pleural effusions to aid counselling and clinical management decisions. METHODS: Retrospective case series of 15 years of congenital pleural effusions resulting in live birth in a single tertiary foetal medicine/neonatal centre in North East England. RESULTS: Data were available for 21 infants. Mortality rates were 43% overall. All spontaneous resolution occurred within 9 d, and active management was used where effusions persisted beyond this. CONCLUSION: Prematurity was associated with a poor prognosis. Resolution without active management occurred before day 10 and active strategies should be considered by this time.

Automated thin-film microextraction coupled to a flow-through cell: somewhere in between passive and active sampling.

A prototype for the automated thin-film microextraction of pharmaceuticals from aqueous solutions has been developed and is presented here for the first time. With a software-controlled setup, extraction methods for ivermectin and iohexol have been developed. The widely used antiparasitic agent ivermectin is non-polar and has a high tendency to sorb to surfaces. In contrast to this, the nonionic but polar iodinated X-ray contrast agent iohexol is freely water soluble. With these two substances, a wide range of polarity is covered. Sorption kinetics and thermodynamics of ivermectin and iohexol were studied. With the presented passive sampling approach, it was possible to extract up to 96.2% ivermectin with a C18-phase within 1 h and up to 74.6% of iohexol with a PS-DVB phase within 36 h out of water. Using abamectin as internal standard, it was possible to quantitatively follow dissipation of ivermectin in a simulated surface water experiment. Predominantly, the newly developed prototype can be used for automated and time-resolved extraction of xenobiotics from waterbodies under field conditions, for the extraction of substances under laboratory conditions as an alternative to the elaborate solid-phase extraction, and for the automated control of chemical reaction kinetics.

Management of large class II lesions in molars: how to restore and when to perform surgical crown lengthening?

The restoration of endodontic tooth is always a challenge for the clinician, not only due to excessive loss of tooth structure but also invasion of the biological width due to large decayed lesions. In this paper, the 7 most common clinical scenarios in molars with class II lesions ever deeper were examined. This includes both the type of restoration (direct or indirect) and the management of the cavity margin, such as the need for deep margin elevation (DME) or crown lengthening. It is necessary to have the DME when the healthy tooth remnant is in the sulcus or at the epithelium level. For caries that reaches the connective tissue or the bone crest, crown lengthening is required. Endocrowns are a good treatment option in the endodontically treated tooth when the loss of structure is advanced.

Trends in Breast Reconstruction by Ethnicity: An Institutional Review Centered on the Treatment of an Urban Population.

Previous studies have investigated reconstructive decisions after mastectomy and such studies document a preference among African American women for autologous tissue-based procedures and among Latin American women for implant-based reconstructions, however, there is a paucity of studies evaluating the current relationship between ethnicity and reconstructive preferences. This institutional review provides a unique, up-to-date evaluation of an understudied urban population composed of majority ethnic minority patients and explores reconstructive trends. Consecutive breast reconstruction patients were entered into a prospectively maintained database at the University of Illinois at Chicago and affiliate hospitals between July 2010 and October 2013. Demographics and oncologic characteristics including tumor stage, pathology, BRCA status, and adjuvant treatment were reviewed, and reconstructive trends were assessed by racial group with a focus on reconstructive procedure, mastectomy volume, and implant characteristics. Statistical analysis was performed using SAS (version 9.2). One-hundred and sixty breast reconstructions were performed in 105 women; of which 50 per cent were African American, 26 per cent Hispanic, 22 per cent Caucasian, and 2 per cent Asian. Age, tumor stage, prevalence of triple negative disease, chemotherapy, and radiation treatment was comparable between groups. Rates of obesity, hypertension, and diabetes mellitus were slightly higher in African American and Hispanic cohorts, with more African American patients having one or more of these comorbidities as compared with the Caucasian and Hispanic cohorts (P = 0.047). Despite comparable positive BRCA testing rates, significant differences were seen in the percentage of bilateral mastectomy; 68 per cent African American, 48 per cent Caucasian, and 30 per cent Hispanic (P = 0.004). Hispanics predominantly underwent flap-based reconstruction (56%), while African American (74%) and Caucasian (60%) patients had a preference toward tissue expander reconstruction (P = 0.04 across all groups). African American and Hispanic presented with increased mastectomy weights and thus required higher implant volumes as compared with Caucasians that approached significance (P = 0.06 and P = 0.06). Implant size utilization followed a unimodal distribution for Caucasians, peaking at 500 cc; while African American and Hispanic demonstrated a bimodal distribution, peaking once at 550 cc and again at the max implant volume of 800 cc. This study of a large proportion of minority patients in an urban geographic setting offers an evolving understanding of breast reconstruction patterns. The data demonstrated unique findings of increased rates of bilateral implant-based reconstruction in African American women and unilateral flap-based reconstructions in Hispanic patients. Reconstructive decision-making seems to be greatly influenced by cultural and geographically driven preferences.

Respiratory Health and Related Quality of Life in Patients with Congenital Agammaglobulinemia in the Northern Region of the UK.

INTRODUCTION: Patients with congenital agammaglobulinemia, characterized by a defect in B lymphocyte differentiation causing B alymphocytosis, require life-long IgG replacement. There is scant literature regarding the effectiveness of IgG treatment at preventing mucosal (particularly sinopulmonary tract) infection and whether current management adequately restores "normal" health and quality of life (QoL). We aimed to document infective episodes pre- and post-commencing IgG replacement, determine any change in lung function and structure and assess respiratory status and QoL in a cohort of patients treated in Newcastle. METHODS: Clinical data were extracted from medical records of 15 patients identified from the immunology database, focusing on infective episodes, serial chest CT and spirometry results. Thirteen patients completed a selection of standardized and validated questionnaires assessing physical health, respiratory health and QoL. RESULTS: Pediatric patients on IgG therapy suffered fewer infections per patient year (0.74) than adults (2.13). 6/14 patients showed deteriorating respiratory status despite adequate therapy. Health questionnaires revealed a significant burden of respiratory disease on a patient's life. CONCLUSION: Clinical data showed patients with congenital agammaglobulinemia receiving immunoglobulin therapy retained a higher than average infection rate, most of which affected mucosal barriers. Most patients self-reported worse respiratory symptoms, a lower respiratory-related QoL and a lower general health QoL relative to a healthy population. Most participants had progressive structural lung damage and decreased lung function. These results suggest that current management is not entirely effective at preventing deterioration of respiratory health or restoring QoL.

Autologous staged fat tissue transfer in post-traumatic lower extremity reconstruction.

Autologous fat tissue transfer for aesthetic reconstruction has been described in the literature for soft tissue damage as early as 1893. One area that has yet to be described is the role of fat grafting in post-traumatic lower extremity injuries. In this case report, we present a patient who had significant injury to her right lower extremity and presented for reconstruction. The patient is a 52-year-old female who presented to clinic after a right lower extremity traumatic injury that required multiple re-operations, which lead to dense scarring and volume loss along the extremity inferior to the knee joint. The patient received two staged autologous fat injections and reported positive outcomes. Our case report demonstrates the utility of fat transfer in reconstruction of the lower extremity in staged fashion. Further research in the refinement of this technique and patient follow-up will lead to better graft survival and reconstructive outcomes.

Toxoplasma gondii in horse meat intended for human consumption in Romania.

The prevalence of Toxoplasma gondii, an economically important zoonotic protozoan, was investigated in horses slaughtered for export and human consumption in the North of Romania. Pairs of samples, sera and heart tissues, were collected from 82 slaughtered horses. Examination of horse sera by ELISA at a dilution of 1:10, and by modified agglutination test (MAT) at a dilution of 1:6, revealed that 32 (39%) and 31(37.8%) horses, respectively, had antibodies against T. gondii. Using polymerase chain reaction (PCR) analysis, T. gondii DNA was not found in any heart sample collected from horses. By bioassay in mice, we obtained viable isolates of T. gondii from two of ten horses determined to be strongly positive by serological assay/ELISA. The prevalence estimated in horses highlighted the potential risk for human contamination by consumption of raw or undercooked meat.