Locally renewing resident synovial macrophages provide a protective barrier for the joint.

Macrophages are considered to contribute to chronic inflammatory diseases such as rheumatoid arthritis1. However, both the exact origin and the role of macrophages in inflammatory joint disease remain unclear. Here we use fate-mapping approaches in conjunction with three-dimensional light-sheet fluorescence microscopy and single-cell RNA sequencing to perform a comprehensive spatiotemporal analysis of the composition, origin and differentiation of subsets of macrophages within healthy and inflamed joints, and study the roles of these macrophages during arthritis. We find that dynamic membrane-like structures, consisting of a distinct population of CX3CR1+ tissue-resident macrophages, form an internal immunological barrier at the synovial lining and physically seclude the joint. These barrier-forming macrophages display features that are otherwise typical of epithelial cells, and maintain their numbers through a pool of locally proliferating CX3CR1- mononuclear cells that are embedded into the synovial tissue. Unlike recruited monocyte-derived macrophages, which actively contribute to joint inflammation, these epithelial-like CX3CR1+ lining macrophages restrict the inflammatory reaction by providing a tight-junction-mediated shield for intra-articular structures. Our data reveal an unexpected functional diversification among synovial macrophages and have important implications for the general role of macrophages in health and disease.

Evaluation of hard palate and cleft morphology in neonates with Pierre Robin Sequence and Cleft Palate Only.

OBJECTIVES: This study aimed to establish a fully digital measurement protocol for standardizing the description of hard palate and cleft morphology in neonates with an isolated cleft palate (CPO) and Pierre Robin sequence (PRS). MATERIALS AND METHODS: A total of 20 digitized plaster models of neonates with CPO and 20 digitized plaster models of neonates with PRS were retrospectively investigated. For the control group, the hard palate was segmented from 21 pre-existing 1.5 T MRI datasets of neonates and exported as an STL file. The digital models were marked with predefined reference points by three raters. Distance, angular, and area measurements were performed using Blender and MeshLab. RESULTS: Neonates with CPO (20.20 ± 2.33 mm) and PRS (21.41 ± 1.81 mm) had a significantly shorter hard palate than the control group (23.44 ± 2.24 mm) (CPO vs. control: P < .001; PRS vs. control: P = .014). Notably, neonates with PRS (33.05 ± 1.95 mm) demonstrated a significantly wider intertuberosity distance than those with CPO (30.52 ± 2.28 mm) (P = .012). Furthermore, there were also significant differences measured between the cleft and control groups (25.22 ± 2.50 mm) (P < .001). CONCLUSIONS: The data from this study demonstrate the feasibility of using MRI datasets to generate digital models of the hard palate. The presence of a cleft palate leads to pronounced adaptations of the total palatal surface area, dorsal width, and length of the hard palate. Mandibular retrognathia and altered tongue position in PRS, as opposed to CPO, might further impact palatal morphology and intertuberosity distance.

New Insights Into the Anatomy of the Eyelashes With Regard to Ethnic Differences Against a Clinical Background.

BACKGROUND: To investigate the root depth, root angle, and light and scanning electron microscopical anatomy of human eyelashes relevant to eyelash ablation. METHODS: Eyelash root depth, the angle between eyelash root and skin epithelium, spatial relationship, and scanning electron microscopical features of the eyelashes were studied on 4 upper and 4 lower eyelids of Caucasian (n = 4) and Indian (n = 4) cadaver heads according to a set protocol. RESULTS: There were significant differences in the mean eyelash root depth between Indians (2.3 ± 0.38 mm) and Caucasians (1.9 ± 0.26 mm; p = 0.007), as well as between upper eyelids and lower eyelids (1.9 ± 0.2 mm vs. 1.8 ± 0.1 mm). The mean angle between the lash follicle root and the skin epithelium was 75 ± 11 degrees and similar in both ethnic groups. The eyelash bulb was located close to the tarsal plate and meibomian glands and formed an angle of less than 15 degrees with the eyelash root. Scanning electron microscopy studies revealed that the eyelash bulb was 202 ± 12 µm wide in Indians and 170.6 ± 16.8 µm wide in Caucasian eyelids ( p = 0.08). The eyelashes were placed more closely in Indian eyelids than in Caucasian eyelids ( p = 0.03). The width of the cuticle layer varied between the hair shaft and the inner eyelid segment. CONCLUSIONS: There are differences in eyelash root depth, inter-eyelash distance, and cuticle thickness between Indian and Caucasian eyelids. The oblique orientation of the eyelash root and close proximity of the eyelash bulb to the tarsal plate should be kept in mind while doing the electroepilation procedure.

Dacryolithogenesis or Dacryolithiasis-The Story So Far.

The term dacryoliths refers to the concretions found within the lacrimal system. When the term dacryoliths is unspecified, it usually refers to the noninfectious dacryoliths commonly isolated from the lacrimal sac and the nasolacrimal duct. More often, they are diagnosed incidentally during a dacryocystorhinostomy, and the reported incidence among all dacryocystorhinostomy surgeries is 5.7% to as high as 18%. Dacryolithiasis is a complex process occurring within the lacrimal system, and current evidence suggests a multifactorial etiology. The sequence of events can be summarized broadly into 4 stages: stage of susceptibility, stage of initiation/trigger, stage of development, and stage of maintenance. The triggering event is the breach of the lacrimal sac or nasolacrimal duct epithelium, resulting in microtrauma with blood leakage. The blood clots act as a nidus for subsequent sequential laying of mucopeptides, cellular debris present locally, debris washed from the ocular surface, and extraneous agents in tears. This process is aided by altered rheology and composition of the tear film. After the formation of dacryoliths, extracellular neutrophil traps usually form on the surface, which help to maintain the dacryoliths (which do not dissolve). This review highlights and discusses the possible sequence of events during dacryolithiasis.

Feasibility of 3 Tesla MRI for the assessment of mid-palatal suture maturation: a retrospective pilot study.

The maxilla occupies a key position in dentofacial orthopaedics, since its transversal development can be directly influenced by orthodontic therapy. The maturation stages of the mid-palatal suture, which are obtained from cone-beam computed tomography images (CBCT), present an addition to clinical decision-making in transversal discrepancies of the upper jaw. In an endeavour to reduce ionizing radiation in adolescents and young adults, who are particularly susceptible to long term stochastic irradiation effects, we investigated the feasibility of 3 Tesla (3T) MRI in detecting the maturation stages of the mid-palatal suture. A collective of 30 patients aged 24-93 years with routine neck MRI at 3T, underwent an additional three-dimensional isotropic T1 weighted study sequence of the midface. Image evaluation was performed on axial, multi-planar formatted reconstructions of the dataset aligned to the midline axis of the palate, and curved reconstructions aligned to the concavity of the palate. Inverted images helped to achieve an image impression similar to the well-known CBCT appearance. All datasets were reviewed by three readers and mid-palatal maturation was scored twice according to Angelieri et al. Intra- and inter-rater agreement were evaluated to measure the robustness of the images for clinical evaluation. 3T MRI deemed reliable for the assessment of mid-palatal suture maturation and hence for the appraisal of the hard palate and its adjacent sutures. The data of this pilot study display the feasibility of non-ionizing cross-sectional MRI for the determination of sutural maturation stages. These findings underline the potential of MRI for orthodontic treatment planning, further contributing to the avoidance of unnecessary radiation doses.

Thermosensitive TRP Channels Are Functionally Expressed and Influence the Lipogenesis in Human Meibomian Gland Cells.

While the involvement of thermosensitive transient receptor potential channels (TRPs) in dry eye disease (DED) has been known for years, their expression in the meibomian gland (MG) has never been investigated. This study aims to show their expression and involvement in the lipogenesis of the MG, providing a possible new drug target in the treatment of DED. Our RT-PCR, Western blot and immunofluorescence analysis showed the expression of TRPV1, TRPV3, TRPV4 and TRPM8 in the MG at the gene and the protein level. RT-PCR also showed gene expression of TRPV2 but not TRPA1. Calcium imaging and planar patch-clamping performed on an immortalized human meibomian gland epithelial cell line (hMGECs) demonstrated increasing whole-cell currents after the application of capsaicin (TRPV1) or icilin (TRPM8). Decreasing whole-cell currents could be registered after the application of AMG9810 (TRPV1) or AMTB (TRPM8). Oil red O staining on hMGECs showed an increase in lipid expression after TRPV1 activation and a decrease after TRPM8 activation. We conclude that thermo-TRPs are expressed at the gene and the protein level in MGs. Moreover, TRPV1 and TRPM8's functional expression and their contribution to their lipid expression could be demonstrated. Therefore, TRPs are potential drug targets and their clinical relevance in the therapy of meibomian gland dysfunction requires further investigation.

Comparative Characterization of Human Meibomian Glands, Free Sebaceous Glands, and Hair-Associated Sebaceous Glands Based on Biomarkers, Analysis of Secretion Composition, and Gland Morphology.

Meibomian gland dysfunction (MGD) is one of the main causes of dry eye disease. To better understand the physiological functions of human meibomian glands (MGs), the present study compared MGs with free sebaceous glands (SGs) and hair-associated SGs of humans using morphological, immunohistochemical, and liquid chromatography-mass spectrometry (LCMS)-based lipidomic approaches. Eyelids with MGs, nostrils, lips, and external auditory canals with free SGs, and scalp with hair-associated SGs of body donors were probed with antibodies against cytokeratins (CK) 1, 8, 10, and 14, stem cell markers keratin 15 and N-cadherin, cell-cell contact markers desmoglein 1 (Dsg1), desmocollin 3 (Dsc3), desmoplakin (Dp), plakoglobin (Pg), and E-cadherin, and the tight junction protein claudin 5. In addition, Oil Red O staining (ORO) was performed in cryosections. Secretions of MGs as well as of SGs of nostrils, external auditory canals, and scalps were collected from healthy volunteers, analyzed by LCMS, and the data were processed using various multivariate statistical analysis approaches. Serial sections of MGs, free SGs, and hair-associated SGs were 3D reconstructed and compared. CK1 was expressed differently in hair-associated SGs than in MGs and other free SGs. The expression levels of CK8, CK10, and CK14 in MGs were different from those in hair-associated SGs and other free SGs. KRT15 was expressed differently in hair-associated SGs, whereas N-cadherin was expressed equally in all types of glands. The cell-cell contact markers Dsg1, Dp, Dsc3, Pg, and E-cadherin revealed no differences. ORO staining showed that lipids in MGs were more highly dispersed and had larger lipid droplets than lipids in other free SGs. Hair-associated SGs had a smaller number of lipid droplets. LCMS revealed that the lipid composition of meibum was distinctively different from that of the sebum of the nostrils, external auditory canals, and scalp. The 3D reconstructions of the different glands revealed different morphologies of the SGs compared with MGs which are by far the largest type of glands. In humans, MGs differ in their morphology and secretory composition and show major differences from free and hair-associated SGs. The composition of meibum differs significantly from that of sebum from free SGs and from hair-associated SGs. Therefore, the MG can be considered as a highly specialized type of holocrine gland that exhibits all the histological characteristics of SGs, but is significantly different from them in terms of morphology and lipid composition.

Historical Profiling of Dry Eye Patients - Potential Trigger Factors and Comorbidities.

PURPOSE: Dry eye syndrome (DES) is one of the most common diseases of the ocular surface. Affected persons suffer from different subjective complaints, with sometimes severe impairment in the quality of life. The aetiology and pathogenesis are multifactorial, multifaceted, and not yet fully understood. The present study is intended to provide deeper insights into possible triggering factors and correlating comorbidities. MATERIALS AND METHODS: In German ophthalmological practices, 306 persons (174 women, 132 men, age: 18 - 87 years) were interviewed by questionnaire on concomitant diseases and possible further triggering factors. DES was diagnosed by an ophthalmologist in 170 cases. The statistical comparative analysis between persons with and without DES was carried out using the chi-squared test (SPSS statistical software). RESULTS: DES occurred with significantly (p < 0.05) increased frequency in women over 40 years of age, as well as in persons exposed to screen work, air conditioning, persons with chronic ocular inflammation, myomas (hysterectomy), dry skin, arterial hypertonicity in need of medication, cardiac arrhythmias, fatty liver, gastric ulcer, appendicitis, cholecystectomy, depression, hyperlipidaemia, hyperuricaemia, osteoporosis, and nephrolithiasis. CONCLUSION: Some of the known comorbidities and DES risk factors, e.g., computer work or depression, were confirmed. In contrast, the higher prevalence of hyperlipidaemia, hyperuricaemia, osteoporosis, nephrolithiasis, and fibroids among DES patients has not previously been reported. Additional studies should be performed on causal connections between DES and specific comorbidities.

Transcutaneous (External) Dacryocystorhinostomy with Reconstruction of the Ductus nasolacrimalis. / Transkutane (externe) Dakryozystorhinostomie mit Rekonstruktion des Ductus nasolacrimalis.

BACKGROUND: Dacryocystorhinostomy (DCR) is regarded as the gold standard for the treatment of chronic dacryocystitis (CDC). Different modifications of the surgical procedure have been developed over the years. METHODS: Patients with CDC due to postsaccal lacrimal stenosis and under treatment with DCR have been included in this retrospective study. Two groups of different surgical procedures were analysed: firstly DCR without reconstruction of the ductus nasolacrimalis (DNL, group 1) and secondly patients with reopening the DNL (group 2). Criteria for success were absence of permanent epiphora, absence of inflammation of the lacrimal sac (functional success), and no recurrent surgery with free patency of the lacrimal duct (anatomical success). This was obtained by questionnaire after a follow-up of at least 12 months. The impact of gender, ectasia of the lacrimal sac, dacryoliths, and prior lacrimal surgeries was analysed. RESULTS: Overall, 248 surgeries were enrolled in this trial. Mean age in group 1 was 68 years (range: 22 to 92 years) and gender ratio was 3.2 to 1 (female : male). In that group, 68 operations could be followed up. In group 2, 62 operations on patients of a mean age of 63 years (range: 24 to 89 years) and a gender ratio of 2.9 to 1 (female : male) were observed. Complete success occurred in 75.0% in group 1 and 75.8% in group 2. Recurrent operations were necessary in one case of group 2 (1.6%) and 4 cases of group 1 (5.9%). Gender (group 1 p = 1; group 2 p = 0.115; between groups p = 0.511), ectasia of the lacrimal sac (group 1 p = 0.877; group 2 p = 0.674; between groups p = 0.878), dacryolith (group 1 p = 1; group 2 p = 0.465; between groups p = 1), and prior lacrimal surgery (group 1 p = 0.092; group 2 p = 0.051; between groups p = 0.520) did not influence the success rates in each group or between groups. Significantly more dacryoliths were found during operations of group 2 (p = 0.010). CONCLUSION: Reconstruction of the DNL during DCR is a possible and easy modification, with a slightly better success rate in curing CDC. Intraoperatively, dacryoliths might not be apparent remain in the deeper parts of the lacrimal ducts. Therefore, these segments should be inspected during surgery.

"Flexures and bends of the large intestine: Current terminology and a suggestion to simplify it".

There are a number of inconsistencies in the description of the bends of the colon down to the anus. This is historically based on the fact that anatomists saw the colon in its position in the abdominal cavity down to the pelvis and thus from the "outside" and also described it in this way. This view is still useful in clinical practice today (e.g. for the abdominal surgeons). For the greater part of clinicians, however, the view has shifted due to modern endoscopy. This allows examiners to see the terminal section of the intestine and the colon from the "inside". To accommodate both "ways of looking" in terms of modern medicine, we have been guided by today's clinical needs, and here we attempt to reconcile these with the historically evolved anatomical terms to create a nomenclature that meets all the needs of students, anatomists and clinicians looking at the large intestine from the inside and outside. With this in mind, we propose to speak of colic flexures (right colic flexure = RCF = hepatic flexure, flexura coli sinistra; left colic flexure = LCF = splenic flexure, flexura coli dextra; descending-sigmoid flexure = DSF; sigmoid-rectum flexure = SRF) for the colon (colon). For the rectum (rectum), we suggest the term bend (superior, intermediate and inferior) when viewed in the frontal plane, the term curvature (sacral curvature; anorectal curvature = perineal curvature) when viewed in the sagittal plane.

The accessory heads of the quadriceps femoris muscle may affect the layering of the quadriceps tendon and potential graft harvest lengths.

PURPOSE: The aim of the study was to assess the quadriceps femoris system for the presence of additional layers. METHODS: One hundred and twenty-eight lower limbs fixed in 10% formalin were examined. RESULTS: Five types of quadriceps tendon layering were found based on the accessory heads of the quadriceps muscle. Type I (55%)-represented by four heads and four layers, and it was something new because standard orthopaedic textbooks described quadriceps tendon as a structure composed of only three layers. Type II (27.4%)-the first four layers were the same as in Type 1, but the accessory tendon of the fifth head of the quadriceps femoris muscle had the deepest attachments. Type III (10.9%)-this type included 6 heads of quadriceps femoris. It consisted of five layers. Type IV (3.1%)-this type included 7 quadriceps femoris heads. This type consisted of only four layers. Type V (3.1%)-this type included 8 heads of the quadriceps femoris heads. This type consist of 5 layers. CONCLUSION: The findings of this study provide a detailed anatomy of the quadriceps tendon including the accessory tendons of the accessory heads of the quadriceps tendon. The accessory heads of the quadriceps femoris muscle contribute to the layering of the quadriceps tendon. The second conclusion of this study is the development of safe distances depending on the types. Not all types are perfect for harvesting-Type IV seems to be the safest type, in turn Type V the most dangerous.

Impact of different cephalometric skeletal configurations on anatomic midface parameters in adults.

OBJECTIVES: Skull morphology and growth patterns are essential for orthodontic treatment, impacting clinical decision making. We aimed to determine the association of different cephalometric skeletal configurations on midface parameters as measured in 3D CT datasets. MATERIALS AND METHODS: After sample size calculation, a total of 240 fully dentulous patients between 20 and 79 years of age (mean age: 42 ± 15), who had received a CT of the skull within the scope of trauma diagnosis or intracranial bleeding, were retrospectively selected. On the basis of cephalometric analysis, using MPR reconstructions, patients were subdivided into three different vertical skull configurations (brachyfacial, mesofacial, dolichofacial) and the respective skeletal Class I, II, and III relationships. Anatomic parameters were measured using a three-dimensional post-processing console: the thickness of the maxillary and palatine bones as well as the alveolar crest, maxillary body and sutural length, width and height of the hard palate, maxillary facial wall thickness, and masseter muscle thickness and length. RESULTS: Individuals with brachyfacial configurations had a significantly increased palatal and alveolar ridge thicknesses compared to those with dolichofacial- or mesofacial configurations. Brachyfacial configurations presented a significantly increased length and thickness of the masseter muscle (4.599 cm; 1.526 cm) than mesofacial (4.431 cm; 1.466 cm) and dolichofacial configurations (4.405 cm; 1.397 cm) (p < 0.001). Individuals with a skeletal Class III had a significantly shorter palatal length (5.313 cm) than those with Class I (5.406 cm) and Class II (5.404 cm) (p < 0.01). Sutural length was also significantly shorter in Class III (p < 0.05). CONCLUSIONS: Skeletal configurations have an impact on parameters of the bony skull. Also, measurable adaptations of the muscular phenotype could result. CLINICAL RELEVANCE: The association between viscerocranial morphology and midface anatomy might be beneficial for tailoring orthodontic appliances to individual anatomy and planning cortically anchored orthodontic appliances.

C1q/TNF-Related Proteins 1, 6 and 8 Are Involved in Corneal Epithelial Wound Closure by Targeting Relaxin Receptor RXFP1 In Vitro.

Inadequate wound healing of ocular surface injuries can lead to permanent visual impairment. The relaxin ligand-receptor system has been demonstrated to promote corneal wound healing through increased cell migration and modulation of extracellular matrix formation. Recently, C1q/tumor necrosis factor-related protein (CTRP) 8 was identified as a novel interaction partner of relaxin receptor RXFP1. Additional data also suggest a role for CTRP1 and CTRP6 in RXFP1-mediated cAMP signaling. However, the role of CTRP1, CTRP6 and CTRP8 at the ocular surface remains unclear. In this study, we investigated the effects of CTRP1, CTRP6, and CTRP8 on epithelial ocular surface wound closure and their dependence on the RXFP1 receptor pathway. CTRP1, CTRP6, and CTRP8 expression was analyzed by RT-PCR and immunohistochemistry in human tissues and cell lines derived from the ocular surface and lacrimal apparatus. In vitro ocular surface wound modeling was performed using scratch assays. We analyzed the effects of recombinant CTRP1, CTRP6, and CTRP8 on cell proliferation and migration in human corneal and conjunctival epithelial cell lines. Dependence on RXFP1 signaling was established by inhibiting ligand binding to RXFP1 using a specific anti-RXFP1 antibody. We detected the expression of CTRP1, CTRP6, and CTRP8 in human tissue samples of the cornea, conjunctiva, meibomian gland, efferent tear ducts, and lacrimal gland, as well as in human corneal, conjunctival, and meibomian gland epithelial cell lines. Scratch assays revealed a dose-dependent increase in the closure rate of surface defects in human corneal epithelial cells after treatment with CTRP1, CTRP6, and CTRP8, but not in conjunctival epithelial cells. Inhibition of RXFP1 fully attenuated the effect of CTRP8 on the closure rate of surface defects in human corneal epithelial cells, whereas the CTRP1 and CTRP6 effects were not completely suppressed. Conclusions: Our findings demonstrate a novel role for CTRP1, CTRP6, and CTRP8 in corneal epithelial wound closure and suggest an involvement of the relaxin receptor RXFP1 signaling pathway. This could be a first step toward new approaches for pharmacological and therapeutic intervention.

Tff3 Deficiency Differentially Affects the Morphology of Male and Female Intestines in a Long-Term High-Fat-Diet-Fed Mouse Model.

Trefoil factor family protein 3 (Tff3) protects the gastrointestinal mucosa and has a complex mode of action in different tissues. Here, we aimed to determine the effect of Tff3 deficiency on intestinal tissues in a long-term high-fat-diet (HFD)-fed model. A novel congenic strain without additional metabolically relevant mutations (Tff3-/-/C57Bl6NCrl strain, male and female) was used. Wild type (Wt) and Tff3-deficient mice of both sexes were fed a HFD for 36 weeks. Long-term feeding of a HFD induces different effects on the intestinal structure of Tff3-deficient male and female mice. For the first time, we found sex-specific differences in duodenal morphology. HFD feeding reduced microvilli height in Tff3-deficient females compared to that in Wt females, suggesting a possible effect on microvillar actin filament dynamics. These changes could not be attributed to genes involved in ER and oxidative stress, apoptosis, or inflammation. Tff3-deficient males exhibited a reduced cecal crypt depth compared to that of Wt males, but this was not the case in females. Microbiome-related short-chain fatty acid content was not affected by Tff3 deficiency in HFD-fed male or female mice. Sex-related differences due to Tff3 deficiency imply the need to consider both sexes in future studies on the role of Tff in intestinal function.

Standardized statement for the ethical use of human cadaveric tissues in anatomy research papers: Recommendations from Anatomical Journal Editors-in-Chief.

Human cadaveric donors are essential for research in the anatomical sciences. However, many research papers in the anatomical sciences often omit a statement regarding the ethical use of the donor cadavers or, as no current standardized versions exist, use language that is extremely varied. To rectify this issue, 22 editors-in-chief of anatomical journals, representing 17 different countries, developed standardized and simplified language that can be used by authors of studies that use human cadaveric tissues. The goal of these editor recommendations is to standardize the writing approach by which the ethical use of cadaveric donors is acknowledged in anatomical studies that use donor human cadavers. Such sections in anatomical papers will help elevate our discipline and promote standardized language use in others non anatomy journals and also other media outlets that use cadaveric tissues.

TRPC Channels in the Physiology and Pathophysiology of the Renal Tubular System: What Do We Know?

The study of transient receptor potential (TRP) channels has dramatically increased during the past few years. TRP channels function as sensors and effectors in the cellular adaptation to environmental changes. Here, we review literature investigating the physiological and pathophysiological roles of TRPC channels in the renal tubular system with a focus on TRPC3 and TRPC6. TRPC3 plays a key role in Ca2+ homeostasis and is involved in transcellular Ca2+ reabsorption in the proximal tubule and the collecting duct. TRPC3 also conveys the osmosensitivity of principal cells of the collecting duct and is implicated in vasopressin-induced membrane translocation of AQP-2. Autosomal dominant polycystic kidney disease (ADPKD) can often be attributed to mutations of the PKD2 gene. TRPC3 is supposed to have a detrimental role in ADPKD-like conditions. The tubule-specific physiological functions of TRPC6 have not yet been entirely elucidated. Its pathophysiological role in ischemia-reperfusion injuries is a subject of debate. However, TRPC6 seems to be involved in tumorigenesis of renal cell carcinoma. In summary, TRPC channels are relevant in multiples conditions of the renal tubular system. There is a need to further elucidate their pathophysiology to better understand certain renal disorders and ultimately create new therapeutic targets to improve patient care.

The Potential Role of SP-G as Surface Tension Regulator in Tear Film: From Molecular Simulations to Experimental Observations.

The ocular surface is in constant interaction with the environment and with numerous pathogens. Therefore, complex mechanisms such as a stable tear film and local immune defense mechanisms are required to protect the eye. This study describes the detection, characterization, and putative role of surfactant protein G (SP-G/SFTA2) with respect to wound healing and surface activity. Bioinformatic, biochemical, and immunological methods were combined to elucidate the role of SP-G in tear film. The results show the presence of SP-G in ocular surface tissues and tear film (TF). Increased expression of SP-G was demonstrated in TF of patients with dry eye disease (DED). Addition of recombinant SP-G in combination with lipids led to an accelerated wound healing of human corneal cells as well as to a reduction of TF surface tension. Molecular modeling of TF suggest that SP-G may regulate tear film surface tension and improve its stability through specific interactions with lipids components of the tear film. In conclusion, SP-G is an ocular surface protein with putative wound healing properties that can also reduce the surface tension of the tear film.

A New Organotypic 3D Slice Culture of Mouse Meibomian Glands Reveals Impact of Melanocortins.

The meibomian glands (MGs) within the eyelids produce a lipid-rich secretion that forms the superficial layer of the tear film. Meibomian gland dysfunction (MGD) results in excessive evaporation of the tear film, which is the leading cause of dry eye disease (DED). To develop a research model similar to the physiological situation of MGs, we established a new 3D organotypic slice culture (OSC) of mouse MGs (mMGs) and investigated the effects of melanocortins on exocrine secretion. Tissue viability, lipid production and morphological changes were analyzed during a 21-day cultivation period. Subsequently, the effects on lipid production and gene expression were examined after stimulation with a melanocortin receptor (MCR) agonist, α-melanocyte-stimulating hormone (α-MSH), and/or an MCR antagonist, JNJ-10229570. The cultivation of mMGs OSCs was possible without impairment for at least seven days. Stimulation with the MCR agonists induced lipid production in a dose-dependent manner, whereas this effect was tapered with the simultaneous incubation of the MCR antagonist. The new 3D OSC model is a promising approach to study the (patho-) physiological properties of MG/MGD while reducing animal studies. Therefore, it may accelerate the search for new treatments for MGD/DED and lead to new insights, such as that melanocortins likely stimulate meibum production.

Common trunk of the internal thoracic artery, inferior thyroid artery and thyrocervical trunk from the subclavian artery: a rare arterial variant.

PURPOSE: In this article, we describe a complex and rare variant of the common trunk arising as a branch of the subclavian artery. This description highlights the clinical relevance of such a variation for medical practice. METHODS: A routine dissection was carried out on an adult 74-year-old female cadaver. After identification and preparation of the common trunk, measurements and photographs were taken. RESULTS: The dissection revealed a common trunk arising from the first part of the left subclavian artery. It divided into the left internal thoracic artery, the inferior thyroid artery, and the thyrocervical trunk. Further on, the branches of the thyrocervical trunk supplied blood to the trapezius muscle, the longus colli muscle and the supraspinatus muscle. CONCLUSION: For the first time, we report the specific appearance of a common trunk from the left subclavian artery that includes the origin of the left internal thoracic artery, inferior thyroid artery, and thyrocervical trunk. Knowledge of the different variations of subclavian branches is essential because of the high frequency with which this region is involved in diagnostic and surgical procedures. LEVEL OF EVIDENCE: II Basic Science Research.

Mediastinal anatomical landmarks, their variants and tips for video-assisted thoracoscopic navigation during oesophageal extirpation.

PURPOSE: There is no systematic description of primary anatomical landmarks that allow a surgeon to reliably and safely navigate the superior and posterior mediastinum's fat tissue spaces near large vessels and nerves during video-assisted endothoracoscopic interventions in the prone position of a patient. Our aim was to develop an algorithm of sequential visual navigation during thoracoscopic extirpation of the esophagus and determine the most permanent topographic and anatomical landmarks allowing safe thoracoscopic dissection of the esophagus in the prone position. METHODS: The anatomical study of the mediastinal structural features was carried out on 30 human cadavers before and after opening the right pleural cavity. RESULTS: For thoracoscopic extirpation of the esophagus in the prone position, anatomical landmarks are defined, their variants are assessed, and an algorithm for their selection is developed, allowing their direct visualization before and after opening the mediastinal pleura. CONCLUSION: The proposed algorithm for topographic and anatomical navigation based on the key anatomical landmarks in the posterior mediastinum provides safe performance of the video-assisted thoracoscopic extirpation of the esophagus in the prone position.