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This study aims to shed light on the transformative potential of artificial intelligence (AI) in the early detection and risk assessment of non-communicable diseases (NCDs). Bibliometric analysis. Articles related to AI in early identification and risk evaluation of NCDs from 2000 to 2024 were retrieved from the Scopus database. This comprehensive bibliometric study focuses on a single database, Scopus and employs narrative synthesis for concise yet informative summaries. Microsoft Excel V.365 and VOSviewer software (V.1.6.20) were used to summarise bibliometric features. The study retrieved 1745 relevant articles, with a notable surge in research activity in recent years. Core journals included Scientific Reports and IEEE Access, and core institutions included the Harvard Medical School and the Ministry of Education of the People's Republic of China, while core countries comprised China, the USA, India, the UK and Saudi Arabia. Citation trends indicated substantial growth and recognition of AI's impact on NCDs management. Frequent author keywords identified key research hotspots, including specific NCDs like Alzheimer's disease and diabetes. Risk assessment studies demonstrated improved predictions for heart failure, cardiovascular risk, breast cancer, diabetes and inflammatory bowel disease. Our findings highlight the increasing role of AI in early detection and risk prediction of NCDs, emphasising its widening research impact and future clinical potential. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired treatable autoimmune disorder. Due to limited availability and affordability of IV immunoglobulins and therapeutic plasma exchange in Pakistan, oral immunosuppressive drugs (ISDs) are used despite limited role in literature. The study aimed to determine the response to ISDs in CIDP patients by assessing the frequency of remission, reduction of disability using a neuropathy related disability score called Inflammatory Neuropathy Cause and Treatment score (or INCAT score), as well as reduction in steroid maintenance dose. The retrospective observational study of six months duration (May to October, 2020) was carried out in Aga Khan University Hospital, Karachi, Pakistan. Medical record of all the patients with idiopathic CIDP taking oral ISDs in last five years was selected which included bio-data, clinical signs and symptoms, medication details, and INCAT scores. Descriptive statistics were described i.e. frequency, percentages, mean/standard deviation using Microsoft Excel v.2021. Out of thirteen patients, Azathioprine was used in nine, Mycophenolate mofetil in two and Cyclosporine in two, with remission (INCAT score improvement ≥ 1) achieved in eight, one and zero patients respectively. Duration of ISDs ranged from three to twenty-four months (average 15.8 months). Patients with monoclonal paraproteinemia and prior exposure to ISDs had a poor response to the introduction of subsequent ISDs. The study describes preliminary experience of the potential role of relatively cheaper and more convenient oral ISDs (especially Azathioprine) as an alternative or sparing agent to first line agents for CIDP and sets the stage for larger scale studies and randomized controlled trials. The aim of this study was to identify and appraise the bibliometric properties of top 100 most-cited articles on regenerative periodontics surgery (RPS). The bibliometric research technique was conducted using a dataset comprising the 100 highly cited articles obtained from Elsevier's Scopus database on RPS. Information regarding the growth of articles by year, number of citations, citations per year, study design, study field, modalities, journals, authors, and countries were extracted for each article. Microsoft Excel (v.16) was utilized for data evaluation and tabulation. These articles on RPS were published over a span of 45 years, from 1975 to 2019, with citation metrics ranging from 144 to 820. Out of the 422 participating authors, 82% contributed to a single article. The 100 most cited articles on RPS were published in 45 years from 1975 to 2019 and number of citations ranged from 144 to 820. Out of the 422 participating authors, 82% contributed in a single article.. The study design with the highest number of cited articles was laboratory/animal studies. Others/not specified was the preferred modality, followed by infrabony modality. The Journal of Periodontology published about one-fourth of the articles, with W. V. Giannobile emerging as the most productive author. Among the 100 most-cited articles on RPS, authors from 25 different countries contributed, with the United States producing half of the articles (n = 51). Bibliometric investigation revealed that the most cited papers published before 2000 had higher citation counts due to their longer period of exposure. The ratio of authors per article increased after the year 2000. Infrabony emerges as a trending topic in RPS, with laboratory/animal studies, clinical trials, and literature reviews being the most frequently employed study designs. To study the impact of reorganization of European hospitals during the most severe phase of the SARS-CoV-2 pandemic on standards of care and early outcomes in patients with periprosthetic fractures. We reviewed available data collected from 14 hospitals in Northern Italy during the quarantine period between March 9 and May 4, 2020. The study included all patients admitted to emergency departments with periprosthetic fractures and scheduled for surgery within a 2-month period. Periprosthetic fractures were classified according to the Uniform Classification System (UCS). Distribution normality was tested using the Kolmogorov-Smirnov test. Accordingly, data were described as non-parametric. Statistical analysis was performed using the Microsoft Excel v. 16.0. In total, 1390 patients admitted to the Department of Orthopedics and Traumatology for emergency care throughout the follow-up period including 38 (2.7%) ones with periprosthetic fractures. There were 12 (31.5%) men and 26 (68.5%) women. Mean age was 81 years (range 70-96). Screening for SARS-CoV-2 by swab was performed in 23 out of 38 patients (60.5%) at admission. It was positive in 2 (5.3%) cases. Three out of thirty-eight patients (7.9%) were diagnosed with COVID-19 due to clinical signs. Of these, 2 patients were diagnosed with COVID-19 before surgery, 3 patients - after surgery. Although the study period coincided with quarantine, the number of admissions for periprosthetic fractures (3%) was similar to that in 2019 and accounted for 3% of the total number of visits to the traumatology and orthopedics departments. The study revealed no obvious changes in hospitalizations for periprosthetic fractures despite social restrictions during the first wave of the COVID-19 pandemic. In emergency, hospitals were still able to provide standard care for patients with periprosthetic fractures despite significant amount of resources redirected for the pandemic. Влияние реорганизации европейских больниц во время наиболее тяжелой фазы пандемии SARS-CoV-2 на стандарты оказания помощи и ранние результаты лечения пациентов с &#x43f

Following Nonablative fractional Fraxel laser (NAFL), a well-established treatment for skin rejuvenation, immediate post-procedural care is essential to address any potential complications and accelerate the healing process. To evaluate the efficacy and patient satisfaction of a topical skincare regimen containing vitamin C, vitamin E, and ferulic acid-CE Ferulic serum (CEF) following NAFL treatment in the Chinese population. In this randomized, investigator-blinded, split-face, controlled trial, patients with mild-to-moderate facial photodamage were randomized to receive CEF treatment on one side of the face and normal saline (NS) on the other side immediately after the NAFL procedure and daily during the 7-day follow-up. The primary endpoint was the change from baseline in erythema score on Day 7, with key secondary endpoints including changes from baseline in erythema index (EI), melanin index (MI), transepidermal water loss, skin hydration, skin sebum content, scabbing, edema, overall patient satisfaction, and post-procedure pain. In total, 50 patients (female 45/50) were enrolled in this study, with a mean age of 31.6 years. The mean change from baseline in erythema score was significantly lower on the CEF side than on the NS side on Day 7 post-NAFL treatment (0.04 ± 0.40 vs. 0.18 ± 0.48, p = 0.011). The CEF side also exhibited improved changes in EI, MI, and skin hydration, as well as higher overall satisfaction and less pain compared with the NS side. Applying CEF after NAFL treatment reduced erythema progression, maintained skin hydration, and promoted the healing process compared with NS. Chinese Clinical Trial Registry: ChiCTR2300069246. Multicentric Castleman's disease (MCD) with cutaneous involvement has rarely been discussed in dermatologic literature, with few reports. Cutaneous lesions in MCD may induce deep scars, causing a significant impact in the daily life of the patients. The treatment of Castleman's disease (CD) is usually a challenge, especially in case of cutaneous involvement. We report the case of a 35-year-old Caucasian man with a 3-year-old history of MCD with cutaneous involvement that we treated with a combined therapy characterized by siltuximab and 1,927 nm fractional laser. The patient showed a therapeutic response, characterized by a reduction of systemic symptoms and cutaneous manifestations. We believe that the combination of siltuximab and 1,927 nm fractional laser might have a synergistic beneficial role in patients with cutaneous iMCD and maximize esthetic outcomes. Anyway, additional evidence is needed to validate our findings. Microbotox technique, intradermal injection of microdroplets of botulinum toxin, is a favorable rejuvenation approach in subjects who prefer more natural appearance. To determine the best injection techniques (dosage, concentration, as well as number and location of injection points), efficacy and side effects of this innovative technique for facial rejuvenation. We conducted a search in Pubmed, Embase, Web of Science, and Google Scholar databases from conception until October 2021 with keywords "microbotox" OR "mesobotox" OR "intradermal injection" AND "botulinum toxin" AND "rejuvenation" AND "wrinkle" AND "face-lift." Twenty articles were included in this review article. Different types of formulation including onabotulinum toxin A (OBA), abobotulinum toxin A (ABO), and incobotulinum toxin A (IBA) were used. The most used concentrations were 10-20 u/cc of OBA. Number of injection points varied from 4 (forehead and periorbital areas) to 999 (entire face) with 2 mm to 2 cm apart. Adjuvant treatment modalities were cross-linked hyaluronic acid, intense pulsed laser, and Fraxel laser. Most studies reported the initial results appeared after 5-14 days of procedure, lasting for nearly 3-6 months. Microbotox is an efficient and attractive method for facial rejuvenation, mid-lower face-lifting, and fine wrinkles reduction in forehead, periocular, and cheek regions, especially in younger-aged subjects. Furthermore, it is a suitable treatment for neck rejuvenation and recontouring of lower mandibular border, particularly in older subjects with marked skin laxity. The Fraxel Dual laser system (Solta Medical, Inc., Bothell, WA) contains a 1,550 and 1,927 nm wavelength single handpiece with different indications for each wavelength. To discuss treatment setting recommendations and best practices for select on-label and investigational applications of the 1,550 and 1,927 nm dual laser system. Eight board-certified dermatologists with 10 or more years of experience with the 1,550 and 1,927 nm laser system completed an online survey about their clinical experience with the system and then participated in a roundtable to share clinical perspectives and best practices for using the laser system. For all Fitzpatrick skin types, treatment recommendations were described for selected approved indications for the 1,550 and 1,927 nm laser system, including both lasers in combination. Treatment recommendations were also reached for investigational applications with the 1,550 nm laser and 1,927 nm laser. Best practices for using the lasers during the treatment session to achieve optimal outcomes and decrease the post-treatment recovery time were compiled. The 1,550 and 1,927 nm dual laser system is effective for a wide range of aesthetic and therapeutic applications, on and off the face and across all Fitzpatrick skin types. Following our survey, we can appreciate that a variety of laser platforms exist to rejuvenate the skin by resurfacing the outer layer of the skin as well as heating the lower layers of the dermis. Based on reliable clinical effectiveness and a limited side effect profile, we can confirm that nonablative fractionated technologies greatly improve the appearance of lentigines, rhytids; eliminate sun damage, attenuate scarring due to acne and other causes; and treat hyperpigmentation. The Fraxel (Solta Medical) laser system delivers pulses across a wide range of density and energy levels. We determined that when increasing the pulse energy this led to an increase in thermolysis microzone depth and width without damaging the surrounding tissue. Due to its performance and various clinical applications, Fraxel laser can be optimally considered to be the gold standard for skin rejuvenation. Sebaceous hyperplasia (SH) is a common skin presentation in adults. Due to their unwanted yellow papular appearance, patients may desire their removal. Although several treatment modalities have been reported, the full range and efficacy of options are unclear. To determine the efficacy of laser modalities in the treatment of SH. The authors will also specifically assess the efficacy, recurrence rate and side effect profile of SH treatment with Er:YAG wavelength using a variable long pulsed (VLP) Er:YAG laser (SP Dynamis Fotona laser, Ljubljana, Slovenia) Methods & Materials: A comprehensive literature search was performed through PubMed, EMBASE, and Web of Science, using the search terms [(sebaceous hyperplasia)] and [(laser[s], Er:Yag, Er:Glass, Fraxel, CO2, PDL, Pulse dye laser, Diode, Xe-Cl, Excimer, Argon, KTP, Ruby, Alexandrite or Nd:YAG)]. The search yielded a total of 119 results and 8 were identified as relevant to this reviewResults: Pulse dye laser (PDL) provides a wide range of treatment results from complete reduction to flattening of the SH without significant adverse events; recurrence rates were unreported. Short PDL showed faster treatment response than long PDL. CO2 laser can produce considerable positive cosmetic outcomes with marked clinical improvement without any recurrence, but significant adverse effects have been reported. The 1450-nm diode laser has been described to produce good (75%) clinical improvement and lesion shrinkage ranging from 50% to greater than 75% without lasting adverse effects. In

Facial aging involves not only soft tissue laxity but also progressive bony resorption, particularly in the maxilla and mandible. Current non-invasive aesthetic modalities primarily target soft tissues, neglecting skeletal changes that contribute to volume loss and structural descent. To propose the hypothetical role of multiwavelength diode laser (MWDL) in stimulating osteogenesis via controlled thermal delivery to the periosteum, offering a novel, non-invasive strategy for counteracting facial bone resorption. This clinical commentary discusses MWDL's mechanism-targeting the periosteal layer using 755, 808, and 1064 nm wavelengths (N.CORE 3D (previous version of Fortra), Classys Inc., Seoul) to deliver 43°C-46°C heat. A case study of a 70-year-old female receiving 16 sessions over 4 years was included. Cortical bone thickness was measured pre- and post-treatment using dental radiographs. Modest increases in cortical bone thickness were observed: from 3.4 to 3.51 mm (left) and from 3.14 to 3.37 mm (right), suggesting possible periosteal osteogenic stimulation. MWDL may represent a promising adjunct to soft tissue rejuvenation by addressing age-related skeletal decline. While early findings are encouraging, controlled trials are needed to validate efficacy, optimise protocols, and define long-term safety.

Acne scarring can impact patients negatively psychosocially. Picosecond lasers and radiofrequency microneedling may be used to improve this condition. To evaluate the efficacy and safety of combination treatment with a picosecond 755-nm Alexandrite laser (PSAL; Picosure Pro; Cynosure, Westford, MA) with diffractive lens array and a radiofrequency microneedling device (RFM; Potenza; Cynosure) for treating facial atrophic acne scars. This was a prospective, single-center, evaluator-blinded, split-face, randomized clinical trial. Twenty subjects with moderate to severe atrophic facial acne scarring were randomized to have one facial half treatment with PSAL followed by full-face treatment with RFM. Subjects received 4 treatments at 4-week intervals. The blinded Investigator's échelle d'évaluation clinique des cicatrices d'acné (ECCA) acne grading, Physician Global Aesthetic Improvement Scale (PGAIS), and Subject Global Aesthetic Improvement Scale (SGAIS) did not show a significant difference between the facial half treated with RFM only and the half treated with RFM and PSAL at interval time points. However, there was significant improvement in ECCA, PGAIS, and SGAIS for both groups over study duration. Both RFM and PSAL appear safe and may be effective for acne scarring treatment, but larger trials are required to confirm superiority or synergy. Studies using a 755 nm picosecond laser with a focus lens array have been reported to be effective for facial wrinkles and pigmentation. This study reports the safety and efficacy using a shorter interval of 2-3 weeks between treatments. Nineteen female subjects and one male subject, primarily Fitzpatrick skin types II and III (one skin type I), who had mild to moderate wrinkles and sun-induced pigmentation were enrolled and treated using the 755 nm PicoSure Laser with focus lens array. The skin was cleansed then wiped with an alcohol wipe prior to treatment. Lidocaine 30% ointment and/or forced air cooling could be used to increase subject comfort. Adjacent pulses, with minimal overlap (10% or less), were delivered to the full face. Subjects received four treatments, performed at 2-3-week intervals. The laser energy used was 0.71 J/cm2 . The physician administered 3-7 passes with an average total of 6,253 pulses per treatment. Follow-up visits occurred at 1 and 3 months post-last treatment at which the physician scored satisfaction and improvement and subjects scored satisfaction and likelihood to recommend to others. The most common side effects were mild swelling, pain, redness, and crusting, most of which subsided within hours of the treatment, with the latest resolving within 48 hours. This is similar to a previous reported study (Weiss et al. ASLMS 2015) where treatments were performed every 6 weeks with side effects resolving within 24 hours. At the 1 and 3 month follow-up visits, 94% (n = 19) and 93% (n = 15) of subjects scored themselves as satisfied or extremely satisfied with their overall results and 81% and 93% were likely to recommend the treatment based on global assessment, respectively. The treating physician was satisfied with 93% of subject's overall results. Three blinded evaluators were able to correctly identify the baseline from post-treatment photographs in 77% of the subjects at the 1 month follow-up and 69% of the subjects at the 3 month follow-up, on average. The average treatment pain score was 4.2 on a 1-10 scale. A compressed treatment interval expedites results without increasing side effects and resulted in a high physician and subject satisfaction rate. Lasers Surg. Med. 48:723-726, 2016. © 2016 Wiley Periodicals, Inc. The use of picosecond lasers to remove tattoos has greatly improved due to the long-standing outcomes of nanosecond lasers, both clinically and histologically. The first aesthetic picosecond laser available for this use was the PicoSure(®) laser system (755/532 nm). Now that a vast amount of research on its use has been conducted, we performed a comprehensive review of the literature to validate the continued application of the PicoSure(®) laser system for tattoo removal. A PubMed search was conducted using the term "picosecond" combined with "laser", "dermatology", and "laser tattoo removal". A total of 13 articles were identified, and ten of these met the inclusion criteria for this review. The majority of studies showed that picosecond lasers are an effective and safe treatment mode for the removal of tattoo pigments. Several studies also indicated potential novel applications of picosecond lasers in the removal of various tattoo pigments (eg, black, red, and yellow). Adverse effects were generally mild, such as transient hypopigmentation or blister formation, and were rarely more serious, such as scarring and/or textural change. Advancements in laser technologies and their application in cutaneous medicine have revolutionized the field of laser surgery. Computational modeling provides evidence that the optimal pulse durations for tattoo ink removal are in the picosecond domain. It is recommended that the PicoSure(®) laser system continue to be used for safe and effective tattoo removal, including for red and yellow pigments.

Optimizing oxygenation for patients necessitates a delicate balance between sufficient oxygen delivery and mitigating the potential hazards of hyperoxemia. We hypothesized that integrating Oxygen Reserve Index (ORi) monitoring would effectively reduce intraoperative hyperoxemia compared to reliance solely on pulse oximetry. This single-center randomized controlled trial included multiple trauma patients with ASA class 3 or higher undergoing general anesthesia. FiO2 adjustments to 0.5 started at T0 with arterial blood gas analysis (ABGA) every 30-minutes. Patients were randomized into Group O (ORi monitoring) and Group N (pulse oximetry). In Group O, FiO2 was reduced if ORi > 0.05; unchanged if ORi was 0-0.05. Group N decreased FiO2 if SpO2 was 100%, unchanged if SpO2 was < 99%, and increased FiO2 by 0.05 until SpO2 reached 95% or above. 54 participants were randomized, and 51 analyzed. Group O demonstrated a significantly higher percentage of normoxemia (80 ≤ PaO2 < 120 mmHg) (64.4% vs. 40.4%, P = 0.002) across 181 ABGAs. Although baseline PaO2 (T1) values were comparable within moderate hyperoxemia, at T2, only Group O achieved normoxemia, with consistently lower PaO2 values at T2, T3, and T4 compared to Group N. ORi values in Group O consistently trended lower from T1 to T4. The positive correlation between PaO2 and ORi was reaffirmed, establishing cut-off values for PaO2 ≥ 120mmHg and ≥ 150mmHg at 0.06 and 0.22, respectively. Simultaneous ORi and pulse oximetry reduce intraoperative hyperoxemia through safe and meticulous protocol adherence in patients. Previous study in human subjects has documented biomechanical and neurophysiological responses to impulsive spinal manipulative thrusts, but very little is known about the neuromechanical effects of varying thrust force-time profiles. Ten adolescent Merino sheep were anesthetized and posteroanterior mechanical thrusts were applied to the L3 spinous process using a computer-controlled, mechanical testing apparatus. Three variable pulse durations (10, 100, 200 ms, force = 80 N) and three variable force amplitudes (20, 40, 60 N, pulse duration = 100 ms) were examined for their effect on lumbar motion response (L3 displacement, L1, L2 acceleration) and normalized multifidus electromyographic response (L3, L4) using a repeated measures analysis of variance. Increasing L3 posteroanterior force amplitude resulted in a fourfold linear increase in L3 posteroanterior vertebral displacement (p < 0.001) and adjacent segment (L1, L2) posteroanterior acceleration response (p < 0.001). L3 displacement was linearly correlated (p < 0.001) to the acceleration response over the 20-80 N force range (100 ms). At constant force, 10 ms thrusts resulted in nearly fivefold lower L3 displacements and significantly increased segmental (L2) acceleration responses compared to the 100 ms (19%, p = 0.005) and 200 ms (16%, p = 0.023) thrusts. Normalized electromyographic responses increased linearly with increasing force amplitude at higher amplitudes and were appreciably affected by mechanical excitation pulse duration. Changes in the biomechanical and neuromuscular response of the ovine lumbar spine were observed in response to changes in the force-time characteristics of the spinal manipulative thrusts and may be an underlying mechanism in related clinical outcomes.

Background and Objectives: Conventional methods for removing cemented fixed prosthetic restorations (FPRs) are unreliable and lead to unsatisfactory outcomes. At their best, they allow the tooth to be saved at the expense of a laborious process that also wears down rotating tools and handpieces and occasionally results in abutment fractures. Restorations are nearly never reusable in any of these situations. Erbium-doped yttrium-aluminum-garnet (Er:YAG) and erbium-chromium yttrium-scandium-gallium-garnet (Er,Cr:YSGG) lasers casafely and effectively remove FPRs, according to scientific studiesre. This study sets out to examine the impact of Er:YAG laser radiation on the debonding of different ceramic restorations, comparing the behavior of various ceramic prosthetic restoration types under laser radiation action and evaluating the integrity of prosthetic restorations and dental surfaces exposed to laser radiation. Materials and Methods: The study included a total of 16 removed teeth, each prepared on opposite surfaces as abutments.y. Based on the previously defined groups, four types of ceramic restorations were included in the study: feldspathic (F), lithium disilicates (LD), layered zirconia (LZ), and monolithic zirconia (MZ). The thickness of the prosthetic restorations was measured at three points, and two different materials were used for cementation. The Er:YAG Fotona StarWalker MaQX laser was used to debond the ceramic FPR at a distance of 10 mm using an R14 sapphire tip with 275 mJ, 20 Hz, 5.5 W, with air cooling (setting 1 of 9) and water. After debonding, the debonded surface was visualized under electron microscopy. Results: A total of 23 ceramic FPRs were debonded, of which 12 were intact and the others fractured into two or three pieces. The electron microscopy images showed that debonding took place without causing any harm to the tooth structure. The various restoration types had the following success rates: 100% for the LZ and F groups, 87% for the LD group, and 0% for the MZ group. In terms of cement type, debonding ceramic FPRs cemented with RELYX was successful 75% of the time, compared to Variolink DC's 69% success rate. Conclusions: In summary, the majority of ceramic prosthetic restorations can be successfully and conservatively debonded with Er:YAG radiation.

Recurrent ERBB2-mutations have been recently documented in a small group of hybrid neurofibroma/schwannoma peripheral nerve sheath tumors (PNST) in patients with presumed sporadic schwannomatosis. Prompted by two cases of plexiform neurofibromas harboring Epidermal Growth Factor Receptor 2 (ERBB2) hot spot mutations, but lacking germline alterations, we sought to investigate the clinicopathologic features of PNST demonstrating this genetic alteration. ERBB2-mutant PNST cases were selected from the institutional molecular database, using a matched tumor-normal targeted DNA sequencing panel. Clinical history, radiologic findings and follow-up information were retrieved from chart review. Pathologic features, genomic and germline findings were reviewed. We identified 5 patients, all except one were females, with a median age of 34 years (range: 24-40). All revealed multiple PNSTs with a segmental distribution by imaging, including pelvis (n=2), upper limb (n=2), and stomach (n=1). None of the patients had family history or displayed clinical features of NF1, except for one patient with faded café-au-lait macules. All excised lesions were neurofibromas, including plexiform (n=4), intraneural with Schwann cell micronodules (n=2), and diffuse (n=1) subtypes. None of the cases showed features of schwannoma. All cases harbored ERBB2 kinase domain mutations (exon 19, n=3, exon 20, n=2, exon 21, n=1). One additional case had two concurrent ERBB2 mutations in exons 20 and 21. By germline testing, only one patient showed pathogenic variants (MUTYH mutation). None showed germline or somatic alterations in NF1, NF2, SMARCB1, LZTR1 or chromosome 22q loss. Patients had stable disease with no significant radiologic progression or malignant transformation; one being enrolled on a HER2-inhibitor trial for 7 years due to unresectable disease with satisfactory disease control. PNST harboring oncogenic ERBB2 mutations are multifocal, spanning various neurofibroma variants, including plexiform type, in the absence of clinical or germline evidence of syndromic disease. Our findings suggest ERBB2 mutations may represent an alternative mechanism driving neurofibroma genesis, with potential therapeutic implications. This chapter traces the evolution of intraventricular hemorrhage in the premature infant highlighting the importance of the germinal matrix, a critical role for cerebral blood flow perturbations in the genesis of hemorrhage, clinical factors that increase bleeding risk, and potential preventative strategies. In the 1970's a neuropathological study demonstrated capillary rupture within the germinal matrix as the source of hemorrhage; loss of cerebral autoregulation in the sick infant was demonstrated. In 1980's the introduction of cranial ultrasound facilitated diagnosis of hemorrhage. Experimental and clinical studies demonstrated the importance of intravascular perturbations in provoking hemorrhage. Specifically, the association of cerebral blood flow velocity fluctuations and subsequent hemorrhage was demonstrated. Surfactant introduction was not associated with a reduction in hemorrhage. In the 1990's antenatal steroids use to accelerate lung development was recommended; this was associated with an unanticipated reduction in hemorrhage. Early indomethacin administration was associated with a reduction of severe hemorrhage. What is the relationship between constitutive CD138 expression in the endometrium and the reproductive tract microbiota composition? The presence of CD138+ cells in endometrial stroma is cycle-dependent and associated with impaired luteal phase endometrial timing but not altered vaginal or endometrial microbial composition. CD138-diagnosed chronic endometritis (CE) is associated with adverse reproductive outcomes including recurrent pregnancy loss (RPL) in uncontrolled studies. However, CD138 is constitutively expressed in the endometrium, potentially confounding the reported associations between CE, adverse endometrial function, and early pregnancy loss. Translational cohort study of a subset of 103 samples derived from 737 women embedded within the CERM trial, a double-blinded, randomized interventional trial evaluating the impact of pre-pregnancy antibiotic treatment for CE in RPL patients. Women aged ≥18 to <42 years, with a history of two or more first-trimester consecutive miscarriages were recruited from specialist RPL clinics. Endometrial biopsies, vaginal, ectocervical, and endometrial swabs were obtained 10 ± 4 days following a positive home ovulation test. Additional samples, including proliferative endometrium, were obtained from the Tommy's National Reproductive Health Biobank. Endometrial biopsies were processed for CD138 expression analysis and immunohistochemistry (IHC), histological dating based on Noyes' criteria, and molecular timing analysis. Metataxonomic profiling of microbiota was performed by sequencing of bacterial 16S ribosomal RNA genes alongside cytokine analysis. IHC revealed three patterns of CD138 immunoreactivity: predominantly membranous punctate staining, predominantly diffuse staining, and a mixed pattern. CD138 is constitutively expressed on the basolateral membrane of glandular epithelial cells and a subset of non-immune stromal cells. Stromal expression was very high (>200 CD138-positive stromal cells/10 mm2) in 26 out of 27 proliferative endometrial samples. While CD138 immunoreactivity in the stroma declines markedly following ovulation (Mann-Whitney U-test; P < 0.005), gene expression analysis demonstrated a reduction in SDC1 expression encoding CD138/syndecan-1, across the menstrual cycle. When compared to CD138-negative samples, conspicuous diffuse staining in the stromal compartment was associated with significantly earlier endometrial histological dating (P < 0.01) and lower molecular timing ratios (P < 0.01). Poor correlation between CD138 and immunoreactivity was demonstrated. Sequencing of paired vaginal and ectocervical swabs and endometrial Tao brush samples collected from 114 patients demonstrated tightly interconnected microbial composition throughout the reproductive tract. No significant difference in vaginal, ectocervical, or endometrial community state type with CD138 expression was demonstrated. Analysis of supernatants of vaginal and ectocervical swabs and Tao Brush revealed an inverse correlation between the severity of stromal CD138 immunoreactivity in endometrial stroma and secreted levels of IL-10, TNF-α, and VEGF (q < 0.05). Microbial and Metataxonomic raw data are available in the European Nucleotide Archive (Projects PRJEB83331 and PRJEB83332). This study relied on patient-reported ovulation-based timing. This was, however, associated with the provision of validated ovulation tests. In addition, the study is limited by lack of collection of data on the underlying fertility-related co-morbidities due to exclusion of known contributory co-morbidities at the point of recruitment. This study challenges the purported relationship between CD138+ CE and the pathophysiology of CE-associated RPL. The findings indicate endometrial CD138 levels are non-immune and non-bacterial driven and are associated with endometrial immaturity. CD138-based CE testing and treatment should not be performed outside of a research context. Funding was provided by the Efficacy and Mechanism Evaluation (EME) Programme a National Institute for Health and Care Research and Medical Research Council partnership (17/60/22). Further funding was from Tommy's National Centre for Miscarriage Research, and the Imperial National Institute for Health and Care Research Biomedical Research Centre Pregnancy and Prematurity Theme. G.D.S.C. is supported by the Genesis Research Trust. All authors report no direct conflict of interest. ISRCTN23947730. In recent years, interest has grown in clarifying t