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Large-scale cell flow characterizes gastrulation in animal development. In amniote gastrulation, particularly in avian gastrula, a bilateral vortex-like counter-rotating cell flow, called 'polonaise movements', appears along the midline. Here, through experimental manipulations, we addressed relationships between the polonaise movements and morphogenesis of the primitive streak, the earliest midline structure in amniotes. Suppression of the Wnt/planar cell polarity (PCP) signaling pathway maintains the polonaise movements along a deformed primitive streak. Mitotic arrest leads to diminished extension and development of the primitive streak and maintains the early phase of the polonaise movements. Ectopically induced Vg1, an axis-inducing morphogen, generates the polonaise movements, aligned to the induced midline, but disturbs the stereotypical cell flow pattern at the authentic midline. Despite the altered cell flow, induction and extension of the primitive streak are preserved along both authentic and induced midlines. Finally, we show that ectopic axis-inducing morphogen, Vg1, is capable of initiating the polonaise movements without concomitant PS extension under mitotic arrest conditions. These results are consistent with a model wherein primitive streak morphogenesis is required for the maintenance of the polonaise movements, but the polonaise movements are not necessarily responsible for primitive streak morphogenesis. Our data describe a previously undefined relationship between the large-scale cell flow and midline morphogenesis in gastrulation.

Background/Objective: A contemporary concept states that dental midline deviation towards the direction of facial flow line (FFL) can mask the compromised smile esthetics. This study aimed to identify a range of midline deviations that can be perceived towards or away from the FFL influencing smile esthetics. Materials and Methods: A cross‐sectional study was conducted using a frontal smile photograph of an adult female. The photograph was altered on Adobe Photoshop software into six different photographs by deviating the dental midlines towards and away from the FFL. A constant deviation of chin towards the left side was incorporated in all the photographs. Forty‐three laypersons (LP) and dental professionals (DPs) evaluated those photographs. Independent t‐test was used to compare the perception of dental midline deviation between LP and DPs. Simple linear regression was run to identify the factors associated with the scoring. Results: A statistically significant difference was observed for picture two with 4 mm towards FFL in the perception of midline deviation between LP and DPs. LP could not perceive the midline deviations up to 4 mm while DPs were able to perceive deviations above 2 mm. The greater the age the better the scores were and female raters had a greater inclination towards poor scores. Conclusions: From 2 to 4 mm of midline deviation towards the FFL can be tolerated by LP and DPs. Clinical Significance: These findings underscore the importance of considering facial symmetry in orthodontic and cosmetic dental treatments to optimize smile esthetics. [ABSTRACT FROM AUTHOR]

A systematic evaluation of vascular access device (VAD) selection incorporates patient, device, and infusate characteristics to ensure optimal device placement. This article explores VAD selection from the perspective of vessel health and preservation and describes VAD selection options and indications, VAD-related complications, and strategies to reduce those complications. [ABSTRACT FROM AUTHOR]

Introduction: Vascular access devices (VADs), namely peripheral VADs (PVADs) and central venous VADs (CVADs), are crucial in both intensive care unit (ICU) and non-ICU settings. However, VAD placement carries risks, notably catheter-related bloodstream infections (CRBSIs). Candida spp. is a common pathogen in CRBSIs, yet its clinical and microbiological characteristics, especially in non-ICU settings, are underexplored. Methods: We conducted a monocentric, retrospective observational study at Luigi Sacco Hospital from 1 May 2021 to 1 September 2023. We reviewed medical records of non-ICU adult patients with CVADs and PVADs. Data on demographics, clinical and laboratory results, VAD placement, and CRBSI occurrences were collected. Statistical analysis compared Candida spp. CRBSI and bacterial CRBSI groups. Results: Out of 1802 VAD placements in 1518 patients, 54 cases of CRBSI were identified, and Candida spp. was isolated in 30.9% of episodes. The prevalence of CRBSI was 3.05%, with Candida spp. accounting for 0.94%. Incidence rates were 2.35 per 1000 catheter days for CRBSI, with Candida albicans and Candida non-albicans at 0.47 and 0.26 per 1000 catheter days, respectively—patients with Candida spp. CRBSI had more frequent SARS-CoV-2 infection, COVID-19 pneumonia, and hypoalbuminemia. Conclusions: During the COVID-19 pandemic, Candida spp. was a notable cause of CRBSIs in our center, underscoring the importance of considering Candida spp. in suspected CRBSI cases, including those in non-ICU settings and in those with PVADs. [ABSTRACT FROM AUTHOR]

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Simple Summary: Diffuse midline gliomas are rare tumors of childhood characterized by a midline location, a diffuse-infiltrative growth pattern, and newly described genetic and epigenetic mutations. Since their first description at the beginning of the 20th century, they have been inoperable and carried a poor prognosis, with median survival shorter than two years. In the last decade, however, new hope is on the horizon thanks to new understanding of these tumors' biology and the development of novel, targeted therapeutics. Diffuse intrinsic pontine glioma (DIPG) was first described by Harvey Cushing, the father of modern neurosurgery, a century ago. Since then, the classification of this tumor changed significantly, as it is now part of the broader family of diffuse midline gliomas (DMGs), a heterogeneous group of tumors of midline structures encompassing the entire rostro-caudal space, from the thalamus to the spinal cord. DMGs are characterized by various epigenetic events that lead to chromatin remodeling similarities, as two decades of studies made possible by increased tissue availability showed. This new understanding of tumor (epi)biology is now driving novel clinical trials that rely on targeted agents, with finally real hopes for a change in an otherwise unforgiving prognosis. This biological discovery is being paralleled with equally exciting work in therapeutic drug delivery. Invasive and noninvasive platforms have been central to early phase clinical trials with a promising safety track record and anecdotal benefits in outcome. [ABSTRACT FROM AUTHOR]

Large-scale cell flow characterizes gastrulation in animal development. In amniote gastrulation, particularly in avian gastrula, a bilateral vortex-like counter-rotating cell flow, called ‘polonaise movements’, appears along the midline. Here, through experimental manipulations, we addressed relationships between the polonaise movements and morphogenesis of the primitive streak, the earliest midline structure in amniotes. Suppression of the Wnt/planar cell polarity (PCP) signaling pathway maintains the polonaise movements along a deformed primitive streak. Mitotic arrest leads to diminished extension and development of the primitive streak and maintains the early phase of the polonaise movements. Ectopically induced Vg1, an axis-inducing morphogen, generates the polonaise movements, aligned to the induced midline, but disturbs the stereotypical cell flow pattern at the authentic midline. Despite the altered cell flow, induction and extension of the primitive streak are preserved along both authentic and induced midlines. Finally, we show that ectopic axis-inducing morphogen, Vg1, is capable of initiating the polonaise movements without concomitant PS extension under mitotic arrest conditions. These results are consistent with a model wherein primitive streak morphogenesis is required for the maintenance of the polonaise movements, but the polonaise movements are not necessarily responsible for primitive streak morphogenesis. Our data describe a previously undefined relationship between the large-scale cell flow and midline morphogenesis in gastrulation.

Introduction: Vascular access devices (VADs), namely peripheral VADs (PVADs) and central venous VADs (CVADs), are crucial in both intensive care unit (ICU) and non-ICU settings. However, VAD placement carries risks, notably catheter-related bloodstream infections (CRBSIs). Candida spp. is a common pathogen in CRBSIs, yet its clinical and microbiological characteristics, especially in non-ICU settings, are underexplored. Methods: We conducted a monocentric, retrospective observational study at Luigi Sacco Hospital from 1 May 2021 to 1 September 2023. We reviewed medical records of non-ICU adult patients with CVADs and PVADs. Data on demographics, clinical and laboratory results, VAD placement, and CRBSI occurrences were collected. Statistical analysis compared Candida spp. CRBSI and bacterial CRBSI groups. Results: Out of 1802 VAD placements in 1518 patients, 54 cases of CRBSI were identified, and Candida spp. was isolated in 30.9% of episodes. The prevalence of CRBSI was 3.05%, with Candida spp. accounting for 0.94%. Incidence rates were 2.35 per 1000 catheter days for CRBSI, with Candida albicans and Candida non-albicans at 0.47 and 0.26 per 1000 catheter days, respectively—patients with Candida spp. CRBSI had more frequent SARS-CoV-2 infection, COVID-19 pneumonia, and hypoalbuminemia. Conclusions: During the COVID-19 pandemic, Candida spp. was a notable cause of CRBSIs in our center, underscoring the importance of considering Candida spp. in suspected CRBSI cases, including those in non-ICU settings and in those with PVADs.

INTRODUCTION: This study aims to understand the relationship between midline deviations and the inherent asymmetry that can be observed in a human face. MATERIALS AND METHODS: A cross-sectional study was conducted using a frontal smile photograph of a female which was altered on Adobe Photoshop software version 23.0 into eight different photographs by deviating the dental midlines by 2 mm, 4 mm, and 6 mm towards and away from the facial flow line (FFL). 4 mm of chin deviation was incorporated in all the pictures except for the first picture in which the midline and chin were kept symmetric. Orthodontic residents evaluated those photographs on an interrupted visual analogue scale (VAS) with 0 being the least attractive and 10 being the most. Simple linear regression was applied to observe factors associated with VAS score. RESULTS: Highest score was observed for picture with midline and chin on (MLCon) with a score of 9.4 ± 0.7, followed by picture with midline on and chin deviated (MLon) 8.7 ± 0.8. The deviations towards green zone received higher scores in comparison to deviations towards red zone. Linear regression revealed highly statistically significant differences between the constant and the rest of the pictures. CONCLUSIONS: The formation of green and red zones by the FFL influences the perception of midline deviation as judged by orthodontic residents. Midline when deviated towards the green zone, was judged to be more aesthetic than when shifted towards the red zones. [ABSTRACT FROM AUTHOR]

Introduction: Despite their precarious behavioral classification (benign and low grade on histopathology yet behaviorally malignant), great strides have been taken to improve prognostication and treatment paradigms for patients with skull base chordoma. With respect to surgical techniques, lateral transcranial (TC) approaches have traditionally been used, however endoscopic endonasal approaches (EEA) have been advocated for midline lesions. Nonetheless, due to the rarity of this pathology (0.2% of all intracranial neoplasms), investigations within the literature remain limited to small retrospective series. Furthermore, radiotherapeutic treatments investigated to date have proven largely ineffective. Methods: Accordingly, we performed a systematic review in order to profile surgical and survival outcomes for skull base chordoma. Fixed and random-effect meta-analyses were performed for categorical variables including GTR, STR, 5-year OS, 10-year OS, 5-year PFS, and 10-year PFS. Additionally, we pooled eligible studies for formal meta-analysis to compare outcomes by surgical approach (lateral versus midline). Statistical analyses were performed using R Studio 'metafor' package or Cochrane Review Manager. Furthermore, meta-analysis of pooled mortality rates and sub-analyses of operative margin and surgical complications were used to compare midline versus lateral approaches via the Mantel-Haenszel method. We considered all p-values < 0.05 to be statistically significant. Results: Following the systematic search and screen, 55 studies published between 1993 and 2022 reporting data for 2453 patients remained eligible for analysis. Sex distribution was comparable between males and females, with a slight predominance of male-identifying patients (0.5625 [95% CI: 0.5418; 0.3909]). Average age at diagnosis was 42.4 ± 12.5 years, while average age of treatment initiation was 43.0 ± 10.6 years. Overall, I2 value indicated notable heterogeneity across the 55 studies [I2 = 56.3% (95%CI: 44.0%; 65.9%)]. With respect to operative margins, the rate of GTR was 0.3323 [95% CI: 0.2824; 0.3909], I2 = 91.9% [95% CI: 90.2%; 93.4%], while the rate of STR was significantly higher at 0.5167 [95% CI: 0.4596; 0.5808], I2 = 93.1% [95% CI: 91.6%; 94.4%]. The most common complication was CSF leak (5.4%). In terms of survival outcomes, 5-year OS rate was 0.7113 [95% CI: 0.6685; 0.7568], I2 = 91.9% [95% CI: 90.0%; 93.5%]. 10-year OS rate was 0.4957 [95% CI: 0.4230; 0.5809], I2 = 92.3% [95% CI: 89.2%; 94.4%], which was comparable to the 5-year PFS rate of 0.5054 [95% CI: 0.4394; 0.5813], I2 = 84.2% [95% CI: 77.6%; 88.8%] and 10-yr PFS rate of 0.4949 [95% CI: 0.4075; 0.6010], I2 = 14.9% [95% CI: 0.0%; 87.0%]. There were 55 reported deaths for a perioperative mortality rate of 2.5%. The relative risk for mortality in the midline group versus the lateral approach group did not indicate any substantial difference in survival according to laterality of approach (-0.93 [95% CI: -1.03, -0.97], I2 = 95%, (p < 0.001). Conclusion: Overall, these results indicate good 5-year survival outcomes for patients with skull base chordoma; however, 10-year prognosis for skull base chordoma remains poor due to its radiotherapeutic resistance and high recurrence rate. Furthermore, mortality rates among patients undergoing midline versus lateral skull base approaches appear to be equivocal. [ABSTRACT FROM AUTHOR]

Epidermoid cysts (ECs) are usually small, benign, keratin-filled cysts, can be congenital or acquired and encountered anywhere in the body. EC and dermoid cyst constitute approximately 7% of all cysts in the head and neck region and tend to occur in areas of embryonic fusion. Neck masses are commonly present in children, and there is often a diagnostic dilemma clinically with common differential diagnoses of this region such as thyroglossal cyst, pre-tracheal lymph nodes, thyroid mass, EC and dermoid cyst. EC is mostly present in middle-aged males, and here, we are going to present an EC of the midline neck in an 8-year-old girl, which is not common. [ABSTRACT FROM AUTHOR]

The aim of the study was to identify the bacterial profile and antimicrobial susceptibility from surgical site cultures in queens and bitches undergoing ovariohysterectomy via ventral midline and lateral flank approaches. Healthy 22 queens and 21 bitches were assigned randomly either ventral midline or lateral flank approach for routine ovariohysterectomy. Surgical site samples were collected before the surgery and on the 1st, 2 nd, and 3 rd days after the surgery for microbiological analysis. A total of 70 different strains were isolated from 50 (29%) of 172 samples. In both queens and bitches the total number of bacteria isolated from the midline approach (n = 50) was found to be higher than in the flank approach (n = 20). The most frequently isolated bacteria were Staphylococcus intermedius group (SIG) (38.5%), followed by Enterococcus faecium (10%) and Staphylococcus lentus (8.5%). Of the isolated Staphylococcus spp. strains were positive 64% for beta-lactam resistance while 52% of that strains were also methicillin-resistant. Multidrug resistance to methicillin, beta-lactamase, and clindamycin was determined in two Staphylococcus spp. isolates. A high level of streptomycin resistance was observed in three Enterococcus faecium isolates. Overall, this study revealed that choosing the surgical site for ovariohysterectomy affected the bacterial profile and more than half of the isolates were resistant to antimicrobials. Thus, the lateral flank approach might be better than the ventral midline approach to prevent possible complications such as a surgical site infection in queens and bitches undergoing ovariohysterectomy. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma (SCC) has several variants based on its histopathological features. Nuclear protein in testis (NUT) carcinoma (NC) is a rare and aggressive variant of SCC, previously described exclusively in midline sites. The histopathological features of NC are similar to poorly differentiated carcinoma or undifferentiated carcinoma. Abrupt keratinization in an otherwise undifferentiated carcinoma is an important diagnostic clue. The confirmatory diagnosis is dependent on molecular techniques such as Immunohistochemistry, Fluorescent in situ hybridization technique or RT-PCR to detect mutations in NUT gene. It is most commonly found in middle aged, in lungs and head and neck regions. Since NC features overlap with poorly differentiated and undifferentiated carcinomas, these cases need to be suspected and evaluated for NUT gene mutations thoroughly. Due to their rarity and less known facts, NC cases are required to be reported on large scale. Here, we report a middle-aged woman with a mass on the forehead diagnosed as NC based on molecular evaluation, with a review of the literature emphasizing the rarity of NUT carcinoma and the importance of careful histopathology as well as immunohistochemistry evaluation. [ABSTRACT FROM AUTHOR]

Gegen Ende der 2. Entwicklungswoche bildet sich mit dem Entstehen des Axialfortsatzes (Initialstadium für die Chorda dorsalis) die sog. morphologische Mittellinie. Dabei unterscheiden wir nach Blechschmidt entwicklungsdynamische Prozesse nach antiapikal (kranial) für das Gesamtei und nach apikal bei der Bildung des Axialfortsatzes. Asymmetrie ist von Beginn an für alle Entwicklungsstadien das vorherrschende Prinzip. Wir unterscheiden die sog. morphologische Mittellinie, kurz Mittellinie, vom osteopathischen Konzept der sog. Midline. Towards the end of the 2nd week of development, the so-called morphological midline is formed with the emergence of the axial process (precursor of the notochord). According to Blechschmidt, for the development of the axial process, we must distinguish between developmental processes in the entire ovum that are anti-apical (cranial) and apical. Asymmetry in growth is the predominant principle from the beginning, for all stages of development. We distinguish the so-called morphological middle line, or median line, from the osteopathic concept of the so-called midline. [ABSTRACT FROM AUTHOR]

High-speed videoendoscopy is a major tool for quantitative laryngology. Glottis segmentation and glottal midline detection are crucial for computing vocal fold-specific, quantitative parameters. However, fully automated solutions show limited clinical applicability. Especially unbiased glottal midline detection remains a challenging problem. We developed a multitask deep neural network for glottis segmentation and glottal midline detection. We used techniques from pose estimation to estimate the anterior and posterior points in endoscopy images. Neural networks were set up in TensorFlow/Keras and trained and evaluated with the BAGLS dataset. We found that a dual decoder deep neural network termed GlottisNetV2 outperforms the previously proposed GlottisNet in terms of MAPE on the test dataset (1.85% to 6.3%) while converging faster. Using various hyperparameter tunings, we allow fast and directed training. Using temporal variant data on an additional data set designed for this task, we can improve the median prediction accuracy from 2.1% to 1.76% when using 12 consecutive frames and additional temporal filtering. We found that temporal glottal midline detection using a dual decoder architecture together with keypoint estimation allows accurate midline prediction. We show that our proposed architecture allows stable and reliable glottal midline predictions ready for clinical use and analysis of symmetry measures.

Introduction: Midline catheters have been reported to be an effective and safe means of providing patients with intravenous access within the hospital and community setting. With minimal experience in the introduction of a midline service across the local health network, a regional hospital pursued this task. This observational study assesses the provision of a safe clinical framework for midline insertion, and the improvement of patient care and experiences by avoiding treatment interruptions and unnecessary cannulation attempts from failed traditional peripheral vascular access devices. Methods: From the introduction of the midline service in June 2018, outcome measures of all patients who received a midline over the following two-year period were documented including rate of line success, complication rates, dwell time, and the number of insertion attempts. Results: The midline service provided 207 lines over a two-year period with a total dwell time of 1,585 days. Project goals were achieved with 85% (Aim > 85%) of all lines completing treatment prior to removal. First attempt insertion was 86% (Aim > 80%) with a maximum insertion attempt of two. Rates of line-related complications were less than 8%, with five documented cases of phlebitis (2.5%) and one deep vein thrombosis with no infections documented. Conclusion: Despite limited resources, a successful midline service was introduced. Future expansion will see an increase in insertor numbers providing improved access to the service. [ABSTRACT FROM AUTHOR]

Aim: Minimally invasive colorectal surgery reduces surgical trauma with better preservation of abdominal wall integrity, but the extraction site is still at risk of incisional hernia (IH). The aim of this study was to determine pooled incidence of IH for each type of extraction site and to compare rates of IH after midline, nonmidline and Pfannenstiel extraction. Method: A systematic review and meta‐analysis was conducted using the PRISMA guidelines. Single‐armed and multiple‐armed cohort studies and randomized controlled trials regarding minimally invasive colorectal surgery were searched from five databases. Outcomes were pooled and compared with random‐effects, inverse‐variance models. Risk of bias within the studies was assessed using the Cochrane ROBINS‐I and RoB 2 tool. Results: Thirty six studies were included, with a total 11,788 patients. The pooled extraction site IH rate was 16.0% for midline (n = 4081), 9.3% for umbilical (n = 2425), 5.2% for transverse (n = 3213), 9.4% for paramedian (n = 134) and 2.1% for Pfannenstiel (n = 1449). Nonmidline extraction (transverse and paramedian) showed significantly lower odds ratios (ORs) for IH when compared with midline extraction (including umbilical). Pfannenstiel extraction resulted in a significantly lower OR for IH compared with midline [OR 0.12 (0.50–0.30)], transverse [OR 0.25 (0.13–0.50)] and umbilical (OR 0.072 [0.033–0.16]) extraction sites. The risks of surgical site infection, seroma/haematoma or wound dehiscence were not significantly different in any of the analyses. Conclusion: Pfannenstiel extraction is the preferred method in minimally invasive colorectal surgery. In cases where Pfannenstiel extraction is not possible, surgeons should avoid specimen extraction in the midline. [ABSTRACT FROM AUTHOR]

Background The development of back pain following epidural analgesia is one reason for patient refusal of neuraxial analgesia. The primary endpoint of this study was to compare the incidence and severity of back pain following midline and paramedian epidural technique. The secondary endpoint was to identify the risk factors associated with the occurrence of back pain. Methods This prospective randomized study included 114 patients receiving thoracic epidural catheterization for pain management following upper abdominal or thoracic surgery. Patients were allocated to either the midline or the paramedian group by computer-generated randomization. An investigator who was blinded to the patient group interviewed patients at 24, and 48 h, and 3–5 days after surgery about the existence of back pain and its severity. Results The total incidence of back pain following epidural anesthesia was 23.8% in the midline group and 7.8% in the paramedian group. The numerical rating scale of back pain was not different between the two groups at 24 h and 4 days after surgery. The paramdian technique was associated with a lower incidence of back pain than the midline technique (95% confidence interval 0.05–0.74, odds ratio 0.2, P < 0.01). However, the number of attempts, surgical position, body mass index, and duration of surgery were not associated with back pain. Conclusions This study showed that the midline group of thoracic epidural analgesia demonstrated higher incidence of back pain than the paramedian group. However, the pain was mild in intensity and decreased with time in both groups.

Background Peripherally inserted central catheters (PICCs) and midlines are commonly used devices for reliable vascular access. Infection and thrombosis are the main adverse effects of these catheters. We aimed to evaluate the relative risk of complications from midlines and PICCs. Methods We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies. The primary outcomes were catheter-related bloodstream infection (CRBSI) and thrombosis. Secondary outcomes evaluated included mortality, failure to complete therapy, catheter occlusion, phlebitis, and catheter fracture. The certainty of evidence was assessed using the GRADE approach. Results Of 8368 citations identified, 20 studies met the eligibility criteria, including 1 RCT and 19 observational studies. Midline use was associated with fewer patients with CRBSI compared with PICCs (odds ratio [OR], 0.24; 95% CI, 0.15–0.38). This association was not observed when we evaluated risk per catheter. No significant association was found between catheters when evaluating risk of localized thrombosis and pulmonary embolism. A subgroup analysis based on location of thrombosis showed higher rates of superficial venous thrombosis in patients using midlines (OR, 2.30; 95% CI, 1.48–3.57). We did not identify any significant difference between midlines and PICCs for the secondary outcomes. Conclusions Our findings suggest that patients who use midlines might experience fewer CRBSIs than those who use PICCs. However, the use of midline catheters was associated with greater risk of superficial vein thrombosis. These findings can help guide future cost-benefit analyses and direct comparative RCTs to further characterize the efficacy and risks of PICCs vs midline catheters. [ABSTRACT FROM AUTHOR]

Background: Deviation of electrode array from the midline of spinal cords affects the therapeutic outcomes of C2-4 cervical spinal cord stimulation (SCS) in patients with disorders of consciousness (DOC). This study proposed the implementation of a novel C2-3 dural exposure procedure and investigated its efficacy compared to conventional surgery. Methods: Surgical and postoperative imaging data from 69 patients with DOC who underwent SCS in the lateral decubitus position were retrospectively assessed. The C2-3 dural exposure procedure was performed in 16 patients while the rest underwent conventional surgery. The incidence of electrode deviation was compared, and factors associated with the deviation were investigated. Results: The rate of complete midline coverage by the electrodes in the C2-3 dural exposure group was significantly higher than the conventional group (93.8% vs. 54.7%, p = 0.004). Exposure of the dura between C2-3 was a significant favorable factor for complete midline coverage by the electrode array (odds ratio [OR]: 0.091; 95% confidence interval [CI]: 0.011--0.757; p = 0.027). Electrode positioned ≥5 cm above the lower edge of the C2 vertebra was a significant risk factor for incomplete midline coverage (OR: 1.126; 95% CI: 1.016--1.248; p = 0.023). No difference in operation time, intraoperative bleeding, or surgical site infection was observed between the 2 groups. Conclusions: The C2-3 dural exposure procedure, performed in the lateral decubitus position, was safe and had higher complete midline coverage than conventional surgery. [ABSTRACT FROM AUTHOR]

Purpose. This study aims to compare the effect of various smile parameters (buccal corridor, gummy smile, midline to face discrepancy, with and without upper lip filling) on the perception of smile attractiveness by applying the digital modification of images judged by one hundred and eighty laypersons from different Middle East populations. Materials and Methods. A frontal photo of a woman's smile is manipulated with Photoshop to modify each smile parameter gradually into 3 grades. The total number of smiles to be assessed is 18. One hundred and eighty participants divided into 3 groups (n=60: 30 men and 30 women): Lebanese, Syrian, and Egyptian laypersons are invited to assess the smile attractiveness before and after modification In addition, each evaluator must indicate which feature she or he finds most attractive in a face. Analysis of repeated measures variances followed by univariate analyses and multiple comparisons of Bonferroni are performed. Results: Eyes and smile are the most attractive elements in the face. For midline to face discrepancy, only Lebanese laypeople and Egyptian women prefer the coincidence of the midline to face compared with other positions with significant difference (p value <0.05). For a gummy smile, women of the 3 populations and the Syrian men tolerate a 2 mm gummy smile, and Lebanese laymen dislike any gingival exposure (p value <0.05). Egyptian men demonstrate no preference (p value> 0.05). Concerning the buccal corridor, its size does not influence smile attractive (p value> 0.05). Upper lip filling affected the perception of smile aesthetics for the midline (for Syrians and Egyptians). Conclusion: Sex and culture affect the perception of the smile attractiveness for certain parameters. Alteration of the buccal corridor does not seem to influence the smile attractiveness. Upper lip filling may be advantageous in some cases and unfavorable in others. Clinical significance: Dentists should take into consideration cultural differences when restoring smile aesthetics. [ABSTRACT FROM AUTHOR]

Pediatric high-grade gliomas (pHGGs) are the leading cause of tumor-related death in children, with diffuse midline gliomas representing the worst prognoses. Despite decades of clinical trials, no effective treatment has been found, and we are in desperate need of novel therapeutics. The discovery of highly recurrent histone H3 mutations in pHGGs represents a major breakthrough in our understanding of tumor initiation and development. In this review, we summarize our current knowledge of the molecular pathology of these tumors, including their genomic/epigenetic alterations, mechanism of action, and partner mutations contributing to tumor progression.

Nuclear Protein in Testis (NUT) carcinomas are rare, extremely aggressive, poorly differentiated squamous carcinoma, characterised by the presence of NUT gene (NUTM1) rearrangement. NUT carcinoma most commonly arises in head and neck region and thorax however, they can occur in other parts of the body also. Here, we are presenting a case series of three cases of NUT carcinoma.All patients were females with disease involving head and neck region. The first case was an eight-year-old girl. The second case was a 36-year-old woman. The third case was a 61-year-old woman. Histopathology of all cases showed poorly differentiated neoplasm, comprising of sheets of monotonous cells with minimal indistinct, clear cytoplasm, round to oval nuclei with prominent nucleoli. High mitotic rate with areas of tumour necrosis were also present. Areas of abrupt keratinisation classically described in this entity were seen in two of the cases. Speckled nuclear positivity for NUT1 monoclonal antibody by immunohistochemistry, which is sensitive and specific for diagnosis was observed in all three cases. There is no definite treatment for this disease, and most patients respond poorly to conventional chemotherapy and radiation. Targeted therapy targeting the BRD4 portion of BRD4-NUT, termed BET bromodomain inhibitors, are in clinical trials. Two of our patients succumbed to disease within one year of diagnosis. Third patient is on follow-up for eleven months after diagnosis.

Background: Patients today seeking esthetic treatment are looking for enhancement of their appearance for improved quality of life. We advocate the use of the term "appearance" in conjunction with the term "esthetics" because it involves a broader assessment of the patient other than the smile. So, in orthodontic diagnosis and treatment planning we have created an approach in evaluation divided into three divisions:1 Macro Esthetics--this includes the profile, vertical facial dimensions--in other words--the face. (2)Mini Esthetics--the smile attributes--buccal corridors, smile arc, incisor display, etc. (3) Micro esthetics--the teeth and their many attributes such as contacts and connectors, embrasures, gingival shape and contour. Aim: The aim of this is to the micro esthetics in patients reporting for orthodontic treatment in Saveetha Dental College. Material and Methods: This is a retrospective clinical study carried out at Saveetha Dental College, Chennai. This study involves the assessment of micro esthetics in patients reporting for orthodontics treatment. The data were taken over a period of 2 years from June 2019 to February 2021. The sample/data were retrieved based on micro esthetics, crown length and width ratio, gingival embrasures, midline, tooth shape. Results: According to the study 66% of the individuals had different crown length and crown width ratio and 34% of individuals had the same crown length and crown width ratio. Most of the patients had midline deviations. Conclusion: Within the limits of the study most of the patients have micro esthetic assessment after orthodontic treatment. [ABSTRACT FROM AUTHOR]

Commissural axons initially respond to attractive signals at the midline, but once they cross, they become sensitive to repulsive cues. In insects and mammals, negative regulation of the surface expression of Roundabout (Robo) receptors prevents premature response to Slit. We previously identified two mammalian Nedd4 interacting proteins, Ndfip1 and Ndfip2, that act analogously to Drosophila Commissureless (Comm) to recruit mammalian Robo1 to late endosomes. However, whether Nedd4 E3 ubiquitin ligases are required for Ndfip-mediated Robo1 regulation and midline axon crossing in vivo is not known. Here, we show using in vitro biochemical techniques and genetic analysis using embryonic mice of either sex that Nedd4-1 and Nedd4-2 are specifically required for Robo1 regulation and spinal commissural axon guidance. Biochemical data indicate that Robo1, Ndfip and Nedd4 form a ternary protein complex that depends on the presence of Ndfip, and these interactions are required for Robo1 endosomal sorting, ubiquitylation and degradation. Nedd4-1 and Nedd4-2 are expressed in commissural neurons in the developing spinal cord, and conditional deletion of Nedd4-1 or Nedd4-2 results in dose-dependent defects in midline crossing. We propose that Nedd4 E3 Ubiquitin ligases and their adaptor proteins Ndfip1 and Ndfip2 constitute a vital intracellular trafficking pathway required to downregulate Robo1 and promote midline crossing of commissural axons. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect magnitude of different parameters on smile attractiveness. Materials and methods: A reference and 13 images were produced by manipulating 13 parameters. Image rating was performed with a 4‐point Likert scale from least attractive (1) to most attractive (4). Image raters included laypeople, dental students, dentists, and dental specialists. Friedman and Wilcoxon image were used for estimate of effect size. Parameters were classified into small (0.10‐ < 0.30), medium (0.30‐ < 0.5), or large (≥0.50). Results: A total of 1040 people participated with good consistency (α = 0.861), and moderate reliability (0.64–0.7). The reference image had the highest rank (laypeople:11.79, dental background: 12.55). For effect size; gingival margin level (−0.11, −0.01), teeth width proportion (−0.09, −0.10), inverted smile arch (−0.09, −0.21), commissure line cant (−0.15, −0.17) and low smile (−0.24, −0.23) had small effect size; occlusal plane cant (−0.36, −0.49), midline cant (−0.36, −0.48), and midline shift (−0.37, −0.49) had medium effect size; diastema (−0.55, −0.54) and color (−0.56, −0.56) had large effect size for the laypeople and dental groups. High smile (−0.42, −0.51), incisor edge symmetry (−0.46, −0.54) had medium effect size in laypeople group and large effect size in the dental group. Width to length tooth proportion (−0.26, −0.39) had small effect size in the laypeople group and medium effect size in the dental group. Conclusions: Smile parameters had different effect magnitude on smile attractiveness and were classified into small, medium, or large parameters. Neither laypeople nor professionals have a collective judgment on what constitutes a beautiful smile. Clinical significance: This study investigated the effect magnitudes of 13 smile parameters and presented a small, medium, and large smile parameters classification. It should provide the clinician with an insight into the expected effect each parameter has on the smile. [ABSTRACT FROM AUTHOR]

Clear aligners have been sought by patients as an aesthetic alternative to conventional orthodontic treatment. Despite the limitation that the aligner system offers, its use has improved over time. Hereby, authors discusses case of a 35-year-old female with Angle's Class I malocclusion patient with severe mandibular crowding who was treated with mandibular incisor extraction using the Invisalign system. Clinical and radiographic examination revealed skeletal Class I malocclusion, severe crowding of the lower incisors, light crowding of the upper incisors, crossbite of the mandibular right canine, a convex profile, prominent lower lip, and a Bolton discrepancy in the lower anterior region. Fourteen trays were used in the maxillary arch and 28 in the mandibular arch. Two additional refinements, one with 13 and the other with 10 trays were delivered. After 2 years and 2 months of active treatment, good posterior occlusion and alignment of the teeth with adequate occlusion function and a balanced smile were achieved. The maxillary retainer was used continuously for 1 year, and at night until now. Successful tooth alignment and space closure were maintained, and the patient was satisfied with the results on the 2 year follow-up. [ABSTRACT FROM AUTHOR]

Introduction: Venous catheters inserted in superficial femoral vein and with mid-thigh exit site have emerged as a feasible and safe technique for central or peripheral tip's venous access, especially in agitated, delirious patients. The spread of multidrug-resistant bacterial (MDR) strains is an emerging clinical problem and more and more patients are being colonized by these types of bacteria. The aim of this study is to evaluate the incidence of central line associated bloodstream infections (CLABSI) or catheter related bloodstream infections (CRBSI) in mid-thigh catheters in patients with positive rectal swabs to evaluate the safety of this procedure and the real infection risk., Methods: In this retrospective observational study, we analyzed data on patients with mid-tight catheters inserted from May 2021 to November 2022. All surveillance rectal swabs were recorded. In addition, to collect data on CLABSI and CRBSI, the results of all blood and catheter tip cultures performed during the hospital stay were acquired., Results: Six hundred two patients were enrolled, 304 patients (50.5%) had a rectal swab; 128 (42.1%) swabs were positive for MDR. Nine CLABSI (only two in patients with a positive rectal swab) and three CRBSI were detected. No statistical difference in the absolute number of CLABSI and CRBSI and in the number of infections per 1000 catheter days emerged between the overall population and patients with positive rectal swabs (respectively p  = 0.45 and p  = 0.53). Similarly, no statistical difference in the number of CLABSI and CRBSI was found among patients with a negative swab and patients with a positive one (respectively p  = 0.43 and p  = 0.51)., Conclusions: According to our data, cannulation of the superficial femoral vein represents a safe location in patients with positive rectal swabs., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Axillary vein in the brachial tract or Basilic vein in the proximal third of the arm has got usually an enough diameter to receive a catheter of 4 or 5 Fr. In this case the exit site should be too proximal to the axilla with an higher risk of infection. Pseudo-tunneling procedure can create an exit site at the middle of the arm without using tunnelers during insertion of Peripherally Inserted Central Catheters and Midlines in patients who present deep veins of the arm too small to receive a catheter to consent infusion and blood samples., Aim: The aim of this study is to present our experience with pseudo-tunneling procedure, also using a particular variation of the technique., Methods: From January 2014 to August 2022 150 Peripherally Inserted Central Catheters and 221 Midlines were insert in pediatric and adults patients with too small deep veins at the middle third of the arm with this technique by the same trained team of Vascular Access Unit at ASST Spedali Civili Hospital of Brescia., Results: All procedures were successfully performed at the first or at the second attempt. No insertion related complications were observed., Conclusions: Our data suggest pseudo-tunneling technique is a safe and effective procedure for of Peripherally Inserted Central Catheters and Midline insertion avoiding central venous catheterization even in patient with small vein at the arms., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

In both vertebrates and invertebrates, commissural neurons prevent premature responsiveness to the midline repellant Slit by downregulating surface levels of its receptor Roundabout1 (Robo1). In Drosophila , Commissureless (Comm) plays a critical role in this process; however, there is conflicting data on the underlying molecular mechanism. Here, we demonstrate that the conserved PY motifs in the cytoplasmic domain of Comm are required allow the ubiquitination and lysosomal degradation of Robo1. Disruption of these motifs prevents Comm from localizing to Lamp1 positive late endosomes and to promote axon growth across the midline in vivo . In addition, we conclusively demonstrate a role for Nedd4 in midline crossing. Genetic analysis shows that nedd4 mutations result in midline crossing defects in the Drosophila embryonic nerve cord, which can be rescued by introduction of exogenous Nedd4. Biochemical evidence shows that Nedd4 incorporates into a three-member complex with Comm and Robo1 in a PY motif-dependent manner. Finally, we present genetic evidence that Nedd4 acts with Comm in the embryonic nerve cord to downregulate Robo1 levels. Taken together, these findings demonstrate that Comm promotes midline crossing in the nerve cord by facilitating Robo1 ubiquitination by Nedd4, ultimately leading to its degradation.