The Evaluation of Virtual Reality Neuroanatomical Training Utilizing Photorealistic 3D Models in Limited Body Donation Program Settings.

Background Neuroanatomy is one of the most complex areas of anatomy to teach to medical students. Traditional study methods such as atlases and textbooks are mandatory but require significant effort to conceptualize the three-dimensional (3D) aspects of the neuroanatomical regions of interest. Objectives To test the feasibility of human anatomy teaching medical students in a virtual reality (VR) immersive environment using photorealistic three-dimensional models (PR3DM) of human anatomy, in a limited anatomical body donation program. Methods We used surface scanning technology (photogrammetry) to create PR3DM of brain dissections. The 3D models were uploaded to VR headsets and used in immersive environment classes to teach second-year medical students. Twenty-eight medical students (mean age 20.11, SD 1.42), among which 19 females (n=28/67.9%) and nine males (n=28/32.1%), participated in the study. The students had either none or minimal experience with the use of VR devices. The duration of the study was three months. After completing the curriculum, a survey was done to examine the results. Results The average rating of the students for their overall experience with the method is 4.57/5 (SD=0.63). The "Possibility to study models from many points of view" and "Good Visualization of the models" were the most agreed upon advantages, with 24 students (n=28, 85.7%), and 95% confidence intervals (CI) [0.6643, 0.9532]. The limited availability of the VR headsets was the major disadvantage as perceived by the students, with 11 students (n=28, 39.3%), 95% CI [0.2213, 0.5927] having voted for the option. The majority of the students (25) (n=28, 89.2%, SD=0.31) agreed with the statement that the use of VR facilitated their neuroanatomy education. Conclusion This study shows the future potential of this model of training in limited cadaver dissection options to provide students with modern technological methods of training. Our first results indicate a prominent level of student satisfaction from VR training with minimum negative reactions to the nature of headsets. The proof of concept for the application of photorealistic models in VR neuroanatomy training combined with the initial results of appreciation among the students predisposes the application of the method on a larger scale, adding a nuance to the traditional anatomy training methods. The low number of headsets used in the study limits the generalization of the results but offers possibilities for future perspectives of research.

The Genotype and Phenotypes in Families (GPF) platform manages the large and complex data at SFARI.

The exploration of genotypic variants impacting phenotypes is a cornerstone in genetics research. The emergence of vast collections containing deeply genotyped and phenotyped families has made it possible to pursue the search for variants associated with complex diseases. However, managing these large-scale datasets requires specialized computational tools tailored to organize and analyze the extensive data. GPF (Genotypes and Phenotypes in Families) is an open-source platform ( https://github.com/iossifovlab/gpf ) that manages genotypes and phenotypes derived from collections of families. The GPF interface allows interactive exploration of genetic variants, enrichment analysis for de novo mutations, and phenotype/genotype association tools. In addition, GPF allows researchers to share their data securely with the broader scientific community. GPF is used to disseminate two large-scale family collection datasets (SSC, SPARK) for the study of autism funded by the SFARI foundation. However, GPF is versatile and can manage genotypic data from other small or large family collections. Our GPF-SFARI GPF instance ( https://gpf.sfari.org/ ) provides protected access to comprehensive genotypic and phenotypic data for the SSC and SPARK. In addition, GPF-SFARI provides public access to an extensive collection of de novo mutations identified in individuals with autism and related disorders and to gene-level statistics of the protected datasets characterizing the genes' roles in autism. Here, we highlight the primary features of GPF within the context of GPF-SFARI.

Portal-site epinephrine injections improve visualisation in arthroscopic rotator cuff repair.

OBJECTIVES: The aim of this study was to evaluate if portal-site injections of 1:200,000 epinephrine improve intraoperative visualisation in arthroscopic rotator cuff repair. METHODS: Patients with partial-thickness supraspinatus tears were selected for the study. They were assigned consecutive numbers and were divided into two groups-control group and intervention group. The surgeries were done by a single surgeon. Every odd-numbered patient was injected. Johnson's visibility classification, surgeon 5-point ordinal Likert scale (LS), and other parameters were recorded. RESULTS: A total of 221 participants (58.4 â€‹± â€‹6.1 years) were selected. Intraoperative visibility was better in the intervention group according to Johnson's classification-satisfactory visibility was achieved in 68 of 110 patients (62%, control group) compared to 89 of 111 patients (80%) (p â€‹= â€‹0.003). Surgeon LS was superior in the intervention group, with a notable decrease in worsened visibility cases. The operative time did not alter statistically significantly-82.2 â€‹± â€‹14.4 â€‹min for the control group, compared to 80.9 â€‹± â€‹10.8 â€‹min in the intervention group (p â€‹= â€‹0.056). No injection-associated complications were recorded. CONCLUSIONS: Portal-site injection of diluted epinephrine solution is safe and improves intraoperative visualisation in arthroscopic rotator cuff repair. This addition does not increase operative time. LEVEL OF EVIDENCE: Level 3, case-control study.

Arthroscopic Extensor Carpi Radialis Brevis Muscle Resection for Chronic Elbow Lateral Epicondylitis.

Recalcitrant elbow lateral epicondylitis presents a difficult challenge for both the patient and the doctor. Surgical treatment consists of open resection and debridement of the extensor carpi radialis brevis muscle. However, advances in arthroscopic surgery provide for a more elegant method. There are several comparative studies between arthroscopic and open treatment that have shown equivalent outcomes. There is no consensus on which treatment is better and no defined indications of when to choose one over the other. This article presents our technique for arthroscopic extensor carpi radialis brevis muscle resection.

Lateral ulnar collateral ligament reconstruction enhancing secondary stabilizers in chronic PLRI of the elbow provides good to excellent clinical results with no recurrent instability.

PURPOSE: The adopted treatment for chronic elbow PLRI is lateral ulnar collateral ligament reconstruction. However, the most frequently reported complication after primary reconstruction is recurrent instability - up to 25 %. It was thus hypothesized that enhancing the secondary stabilizers will provide successful results with a lower rate of recurrent instability in comparison to techniques with primary reconstruction only. This study aimed to demonstrate a novel surgical technique involving secondary stabilizers. METHODS: In this retrospective study of 29 cases with chronic PLRI the mean duration of symptoms was 39.6 ± 4.9 months. The mean age was 47.9 years with mainly male patients. The surgeries were performed by one senior surgeon at a single institution. The Mayo Elbow Performance Score (MEPS) and the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) were recorded. RESULTS: The mean follow-up was 36.8 ± 7.7 months. The MEPS score improved significantly from 59.8 ± 13.1 to 84.7 ± 7.6 (p < 0.001). 23/29 patients (79.2 %) had converted to good and excellent results (MEPS >75 points). The DASH score improved from 40.8 ± 4.6 to 20.9 ± 7.2 (p < 0.001). The total complication rate was 10.3 % (N = 3). No recurrent instability was recorded in comparison to 12.2 % for primary reconstruction only, as reported in the literature (p < 0.05). CONCLUSION: Enhancing the secondary stabilizers by utilizing an adjacently located autograft provided good and excellent results with no recurrent instability. This novel surgical procedure is easy to reproduce and provides a safe and reliable alternative in cases of chronic PLRI when compared to techniques with primary reconstruction only.

Copper-Based Nanomaterials for Fine-Pitch Interconnects in Microelectronics.

ConspectusNanostructured copper-based materials have emerged as a new generation of robust architectures for realizing high-performing and reliable interconnection in modern electronic packaging. As opposed to traditional interconnects, nanostructured materials offer better compliance during the packaging assembly process. Due to the high surface area-to-volume ratio of nanomaterials, they also enable joint formation by sintering through thermal compression at much lower temperatures compared to bulk counterparts. Nanoporous Cu (np-Cu) films have been employed in electronic packaging as materials that facilitate a chip-to-substrate interconnection, realized by a Cu-on-Cu bonding after sintering.In this Account, we discuss the use of self-supported np-Cu films for low-temperature joint formation. The novelty of this work comes from the incorporation of tin (Sn) into the np-Cu structure, thus ensuring lower sintering temperatures with a goal of producing Cu-Sn intermetallic alloy-based joints between two Cu substrates. The incorporation of Sn is done using an all-electrochemical bottom-up approach that involves the conformal coating of fine-structured np-Cu (initially formed by dealloying of Cu-Zn alloys) with a thin layer of Sn.This Account provides insight on existing technologies for using nanostructured films as materials for interconnects as well as the optimization studies for the Sn-coating processes as a new alternative approach. The applicability of the synthesized Cu-Sn nanomaterials for low-temperature joint formation is also discussed. To realize this new approach, the Sn-coating process is administered by a galvanic pulse plating technique, which is optimized to preserve the porosity in the structure with a Cu/Sn atomic ratio that allows for the formation of the Cu6Sn5 intermetallic compound (IMC). Nanomaterials obtained using this approach are subjected to joint formation by sintering at temperatures between 300 and 200 °C under 20 MPa pressure in forming gas atmosphere. Cross-section characterization of the formed joints postsintering reveals densified bonds with minimal porosity that consist predominantly of the Cu3Sn IMC. Furthermore, these joints are less prone to structural inconsistencies compared to existing joints formed using purely np-Cu. The results presented in this Account provide a glimpse into a facile and cost-effective approach for synthesizing nanostructured Cu-Sn films and illustrate their applicability as new interconnect materials.

Three-Dimensional Immersive Photorealistic Layered Dissection of Superficial and Deep Back Muscles: Anatomical Study.

Introduction The distinct anatomy of the superficial and deep back muscles is characterized by complex layered courses, fascial planes, specific vascularization, and innervation. Knowledge of these anatomical parameters is important for some surgical approaches, including lumbar disc herniation, cerebrospinal fluid fistula repair, vascularized muscle pedicle flaps, and posterior fossa extra-intracranial bypass. In the present study, we use modern techniques of three-dimensional (3D) surface scanning to help better illustrate the layered anatomy of the back muscles. Material and methods We dissected in layers the back muscles of one cadaver. Every step of the dissection was 3D scanned using a technique called photogrammetry, which allows the extraction of 3D data from 2D photographs. The 3D data were processed using Blender software, and the 3D photorealistic models were uploaded to a dedicated website for 3D visualization. This allows users to see the 3D models from every desktop or mobile device, as well as augmented (AR) and virtual reality (VR) formats. Results The photorealistic 3D models present the back muscles' anatomy in a volumetric manner, which can be visualized on any computer device. The web 3D features, including AR and VR, allow users to zoom, pan, and rotate the models, which may facilitate learning. Conclusion The technology of photorealistic surface scanning, modern 3D visualization possibilities of web-dedicated formats, as well as advances in AR and VR, have the potential to help with a better understanding of complex anatomy. We believe that this opens the field for further research in the field of medical education.

A systematic review of elbow arthroscopy complications : Complications, risk factors, and safety tips.

PURPOSE: To determine the complications from elbow arthroscopy for the past 16 years, and to summarize the most reported safety techniques and risk factors. METHODS: Eligibility criteria included level I to IV evidence articles that were published after 2005 in the English language. Excluded were vet, paediatric, and cadaver studies. Open and arthroscopic-assisted elbow procedures were not included. Two online databases were comprehensively searched (PubMed and PMC) in April 2021. Relevant paper selection was conducted by two independent reviewers. MINORS score, demographic properties, indications, procedure type, complication rates, reoperation rates, reported risk factors, and safety techniques were recorded. RESULTS: Fifty-two articles met the criteria and were included. No relevant level I to II evidence studies were discovered. The mean age ranged from 31 to 65 years. The average body mass indexes were between 26 and over 40 kg/m2. There was a prevalence of male sex (from 50.2 to 79.2%). Most of the studies reported a minimum follow-up (range, 4 weeks-12 months). The most common arthroscopic procedure was debridement (up to 73% in Leong et al.'s study). The average MINORS score was 12 (range, 10-16). The total complications rate ranged from 1.5 to 11%, with a few studies reporting over 25%. Nerve injury rate was 1.26-7.5%. Re-operation rate ranged from none (100 procedures) to 11.8%. CONCLUSIONS: Elbow arthroscopy is a successful procedure with a low overall complications rate (from 1.5 to 11%), and a low nerve injury rate (from 1.26 to 7.5%). Risk factors include patient-related factors (obesity, female sex, age over 65 years, elevated blood sugar levels, hypercoagulable disorder, tobacco and alcohol use), preoperative elbow impairment/previous surgery, and periprocedural steroid injections. Our review discovered a re-operation rate of 2 to 18%.

A Challenging Case of Using Manta Ray Skin Flaps in a Severe Post-Traumatic First Web Space Contracture.

BACKGROUND First web space contracture affects thumb function and grasping capacity. This pathology alters normal anatomy and results in decreased ability to use the hand. Appropriate release and resurfacing are needed to restore normal hand function. Principles of successful treatment also include providing healthy compliant skin for a tension-free closure and a smooth healing period. The Manta Ray skin flaps are utilized in children, allowing the position of as much local skin as possible with minimal dorsal scarring. The technique has potential use in adults who have less skin plasticity and pliability. CASE REPORT We present the case of a 36-year-old patient with a severe first web space contracture of the dominant hand. Primary concerns of the patient were loss of hand mobility, limited grasping ability, and an inability to "give a proper handshake". Medical history suggests a gunshot wound in early childhood treated operatively by a mild web release after the point of trauma, with insufficient outcomes. We proceeded with the Manta Ray flap technique using 3 dorsally-based flaps and 4 palmar-based flaps, with excellent results. CONCLUSIONS Although the Manta Ray flap procedure was developed for moderate web space contractures in children, it combines advantages of several flap techniques. It ensures sufficient web space lengthening and may be applicable in older patients if enough healthy unscarred skin is available. These unique properties and potential led us to use the method for this challenging case.

Pelvic Lymphadenectomy in Gynecologic Oncology-Significance of Anatomical Variations.

Pelvic lymphadenectomy is a common surgical procedure in gynecologic oncology. Pelvic lymph node dissection is performed for all types of gynecological malignancies to evaluate the extent of a disease and facilitate further treatment planning. Most studies examine the lymphatic spread, the prognostic, and therapeutic significance of the lymph nodes. However, there are very few studies describing the possible surgical approaches and the anatomical variations. Moreover, a correlation between anatomical variations and lymphadenectomy in the pelvic region has never been discussed in medical literature. The present article aims to expand the limited knowledge of the anatomical variations in the pelvis. Anatomical variations of the ureters, pelvic vessels, and nerves and their significance to pelvic lymphadenectomy are summarized, explained, and illustrated. Surgeons should be familiar with pelvic anatomy and its variations to safely perform a pelvic lymphadenectomy. Learning the proper lymphadenectomy technique relating to anatomical landmarks and variations may decrease morbidity and mortality. Furthermore, accurate description and analysis of the majority of pelvic anatomical variations may impact not only gynecological surgery, but also spinal surgery, urology, and orthopedics.

Visible Meridian Phenomena after Acupuncture: A Series of Case Reports.

Background: In accordance with the meridian theory of Traditional Chinese Medicine (TCM), meridian phenomena are observed along the course of a meridian following acupuncture. Their visible manifestations include alterations in the color (reddening or whitening) of the skin as well as papule and vesicle formation. Objectives: The aim of the present work is to report a series of visible meridian phenomena manifested in human subjects and to correlate them to TCM concepts. A total of 1,200 patients, on whom classical acupuncture (with standard single-use needles without electrostimulation or moxibustion) was applied, were carefully observed and documented. Methods: Visible meridian phenomena were photographed using standard photographical equipment and compared to classical acupuncture channels used by TCM. Results: Ten patients (5 male, 5 female) exhibited visible meridian phenomena. Lines, concurring with the meridians, were observed: white lines in seven cases and red lines in three cases. The duration of the two kinds of phenomena was different. White lines remained visible for a shorter period (10-15 min), whereas red lines were seen for up to one hour after needle removal. Conclusion: These observations indicate that visible meridian phenomena following acupuncture are objective, albeit rare, findings that coincide with the acupuncture channels described in the classical works of TCM. The presence of such phenomena provides a new insight into the concept of meridians and explains the development of the idea in its historical context.

Histochemical and immunohistochemical localization of nitrergic structures in the carotid body of spontaneously hypertensive rats.

The carotid body (CB) is a multipurpose metabolic sensor that acts to initiate cardiorespiratory reflex adjustments to maintain homeostasis of blood-borne chemicals. Emerging evidence suggests that nitric oxide increases the CB chemosensory activity and this enhanced peripheral chemoreflex sensitivity contributes to sympathoexcitation and consequent pathology. The aim of this study was to examine by means of NADPH-diaphorase histochemistry and nitric oxide synthase (NOS) immunohistochemistry the presence and distribution of nitrergic structures in the CB of spontaneously hypertensive rats (SHRs) and to compare their expression patterns to that of age-matched normotensive Wistar rats (NWRs). Histochemistry revealed that the chemosensory glomus cells were NADPH-d-negative but were encircled by fine positive varicosities, which were also dispersed in the stroma around the glomeruli. The NADPH-d-reactive fibers showed the same distributional pattern in the CB of SHRs, however their staining activity was weaker when compared with NWRs. Thin periglomerular, intraglomerular and perivascular varicose fibers, but not glomus or sustentacular cells in the hypertensive CB, constitutively expressed two isoforms of NOS, nNOS and eNOS. In addition, clusters of glomus cells and blood vessels in the CB of SHRs exhibited moderate immunoreactivity for the third known NOS isoenzyme, iNOS. The present study demonstrates that in the hypertensive CB nNOS and eNOS protein expression shows statistically significant down-regulation whereas iNOS expression is up-regulated in the glomic tissue compared to normotensive controls. Our results suggest that impaired NO synthesis could contribute to elevated blood pressure in rats via an increase in chemoexcitation and sympathetic nerve activity in the CB.

Is the Newly Described Interstitial Network the Anatomical Basis of Acupuncture Meridians? A Commentary.

A network passing through interstitial tissues of the human body has been recently described. Despite its functional importance is yet unknown, we try to briefly summarize the known data and to interpret it from the viewpoint of Traditional Chinese medicine. We consider the peculiarities of the interstitium to be the morphological basis of at least some of the known phenomena along acupuncture meridians.

Effects on the quality and health-enhancing properties of industrial onion waste powder on bread.

Industrial onion waste powder (IOWP) was used as an additive in wheat flour at different levels: 0, 1, 2, 3, 4 and 5%. The effect of onion waste addition on the mixing properties of the dough and quality of bread was investigated. The mixing properties of the dough were determined by farinograph. The bread were characterized and evaluated for crumb hardness, crumb porosity, sensory properties, dietary fiber, total phenolic content and total flavonoids. DPPH and FRAP assays were carried out to measure antioxidant activity in vitro. The results indicated that IOWP could be used as a potential health-enhancing functional ingredient up to 3% level to produce bread enriched with dietary fiber, total phenolic compounds and total flavonoids, and characterized by high antioxidant activity and acceptable quality.

Immunohistochemical localization of angiotensin AT1 receptors in the rat carotid body.

The carotid body (CB) is a major peripheral arterial chemoreceptor that initiates respiratory and cardiovascular adjustments to maintain homeostasis. Recent evidence suggests that circulating or locally produced hormones like angiotensin II acting via AT1 receptors modulate its activity in a paracrine-autocrine manner. The aim of this study was to examine the immunohistochemical localization of AT1 receptor in the CB of adult rats and to compare its expression in vehicle-treated animals, and after the long-term application of its selective blocker losartan. Immunohistochemistry revealed that a subset of CB glomeruli and the vast majority of neurons in the adjacent superior cervical ganglion (SCG) were strongly AT1 receptor-immunoreactive. In the CB immunostaining was observed in the chemosensory glomus cells typically aggregated in cell clusters while the nerve fibers in-between and large capillaries around them were immunonegative. Exogenous administration of losartan for a prolonged time significantly reduces the intensity of AT1 receptor immunostaining in the CB glomus cells and SCG neurons. Our results show that AT1 receptors are largely expressed in the rat CB under physiological conditions, and their expression is down-regulated by losartan treatment.

Highly Active and Durable Cu x Au(1-x) Ultrathin-Film Catalysts for Nitrate Electroreduction Synthesized by Surface-Limited Redox Replacement.

Cu x Au(1-x) bimetallic ultrathin-film catalysts for nitrate electroreduction have been synthesized using electrochemical atomic layer deposition by surface-limited redox replacement of Pb underpotentially deposited layer. Controlled by the ratio of [Cu2+] ions and [AuCl4 -] complex in the deposition solution, the alloy film composition (atomic fraction, x in the range of 0.5-1) has been determined by X-ray photoelectron spectroscopy and indirectly estimated by anodic stripping voltammetry. The catalytic activity and durability of Cu x Au(1-x) thin films, Cu thin film, and bulk Cu have been studied by one- and multiple-cycle voltammetry. The synthesized Cu x Au(1-x) thin films feature up to two times higher nitrate electroreduction activity in acidic solution compared to bulk and thin-film Cu counterparts. Highest activity has been measured with a Cu0.70Au0.30 catalyst. Durability tests have demonstrated that Cu thin films undergo rapid deactivation losing 65% of its peak activity for 92 cycles, whereas Cu0.70Au0.30 catalysts lose only 45% of their top performance. The significantly better durability of alloy films can be attributed to effective resistance to poisoning and/or hindered dissolution of Cu active centers. It has been also found that both Cu x Au(1-x) and pure Cu thin films show best electroreduction activity at lowest pH.

Acupuncture causes serotonin release by mast cells.

Mast cells (MCs) are important object in experimental acupuncture due to their putative involvement in local reactions to needling. In the rat, they are shown to contain in their granules, among other tissue mediators, serotonin, also called 5-hydroxytryptamine (5-HT). The aim of this study is to examine the normal distribution of 5-HT-containing MCs in soft tissues of Zusanli (ST36) acupuncture point (acupoint) and their morphological changes caused by experimental acupuncture. We observed 5-HT-immunopositive MCs in the tissues and in the vicinity of the needle tract formed after acupuncture. As a result of acupuncture needling, the tissue integrity is disrupted and certain folds are formed in the direction of the needle tract. Connective tissue in the vicinity of the needle tract gets compressed and displaced, together with the 5-HT-immunoreactive MCs seen there. Some of those 5-HT-immunopositive MCs showed signs of degranulation with numerous discharged granules, some of them found at a considerable distance form the cell. Furthermore, 5-HT-immunopositive MCs are unevenly distributed in soft tissues of ST36 acupoint. Larger numbers of 5-HT-containing MCs were visualized in subcutis and dermis, compared to the observed in striated muscles. Placing the acupuncture needle into the rat skin caused a formation of an apparent needle tract, tissue displacement and degranulation of 5-HT-immunopositive MCs. The demonstrated serotonin release by means of MC degranulation might be involved in the local tissue response to acupuncture.

Clinical Characteristics of Ulceroglandular Tularemia in Two Bulgarian Regions, 2014-2015: a Report of Five Cases.

We present here the first five human cases with tularemia from two regions in South Bulgaria in which there had been no previous report of the infection. The cases occurred over a period of 8 months (December 2014 - August 2015). They were treated at the Department of Infectious Diseases in Stara Zagora University Hospital, Bulgaria. We present the clinical, epidemiological and laboratory data for four men and one woman (age range 52 to 73 years). Three men were hunters, four patients took part in handling, preparing/skinning and cooking the game animals. One man marked agricultural work and contact with straw stems. After a mean incubation period of 4.8±1.4 days ulcers appeared, followed by local painful lymphadenitis. All patients presented with liver enlargement and elevation in acute phase reactants. The etiological diagnosis was made by tube agglutination test in all cases, PCR positive result was found in one. The administered antibacterial treatment was a combination of aminoglycosides and 4-quinolones with the outcome being favorable for all patients. The current report suggests presence of Francisella tularensis in South Bulgaria.

Expression of nitric oxide-containing structures in the rat carotid body.

The carotid body (CB) is a major peripheral arterial chemoreceptor organ that evokes compensatory reflex responses so as to maintain gas homeostasis. It is dually innervated by sensory fibers from petrosal ganglion (PG) neurons, and autonomic fibers from postganglionic sympathetic neurons of the superior cervical ganglion (SCG) and parasympathetic vasomotor fibers of intrinsic ganglion cells in the CB. The presence of nitric oxide (NO), a putative gaseous neurotransmitter substance in a number of neuronal and non-neuronal structures, was examined in the CB, PG and SCG of the rat using nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry, nitric oxide synthase (NOS) immunohistochemistry and retrograde tracing. One week after injecting the retrograde tracer Fast Blue (FB) in the CB, we found that a subset of perikarya in the caudal portions of the PG and SCG were FB-labeled. Histochemistry and immunohistochemistry revealed that the majority of large- and medium-sized PG and SCG cells were NADPH-d positive and displayed a strong NOS immunostaining. We also observed that many varicose nerve fibers penetrating the CB and enveloping the glomus cells and blood vessels were NADPH-d reactive and expressed the constitutive isoforms of NOS, nNOS and eNOS. In addition, some autonomic microganglion cells embedded within, or located at the periphery of the CB, and not glomus or sustentacular cells were nNOS-immunopositive while CB microvasculature expressed eNOS. The present results suggest that NO is a transmitter in the autonomic nerve endings supplying the CB and is involved in efferent chemoreceptor inhibition by a dual mechanism.

Metformin and Angiogenesis in Cancer - Revisited.

Several clinical studies demonstrated that diabetic patients treated with metformin were less likely to develop vascular complications, independent of glycemic control. It was also demonstrated that the large variety of metformin's vascular actions can be seen in nondiabetic conditions. Metformin has an interesting potential to treat vascular dysfunction and tumor angiogenesis in conditions beyond diabetes. Since metformin's use in cancer as a single antiangiogenic agent appears to be a therapeutic disappointment, the use of the drug as part of combination anticancer modality represents a therapeutic challenge. The normalization of vascular dysfunction as a new therapeutic strategy may provide better delivery of conventional anticancer agents to the tumor and disrupted tumor environment. In this review, we will outline the available information from the literature regarding metformin and tumor angiogenesis and suggest eventual experimental and clinical approaches.