Double-Clad Antiresonant Hollow-Core Fiber and Its Comparison with Other Fibers for Multiphoton Micro-Endoscopy.

Label-free and multiphoton micro-endoscopy can transform clinical histopathology by providing an in situ tool for diagnostic imaging and surgical treatment in diseases such as cancer. Key to a multiphoton imaging-based micro-endoscopic device is the optical fiber, for distortion-free and efficient delivery of ultra-short laser pulses to the sample and effective signal collection. In this work, we study a new hollow-core (air-filled) double-clad anti-resonant fiber (DC-ARF) as a high-performance candidate for multiphoton micro-endoscopy. We compare the fiber characteristics of the DC-ARF with a single-clad anti-resonant fiber (SC-ARF) and a solid core fiber (SCF). In this work, while the DC-ARF and the SC-ARF enable low-loss (<0.2 dBm-1), close to dispersion-free excitation pulse delivery (<10% pulse width increase at 900 nm per 1 m fiber) without any induced non-linearities, the SCF resulted in spectral broadening and pulse-stretching (>2000% of pulse width increase at 900 nm per 1 m fiber). An ideal optical fiber endoscope needs to be several meters long and should enable both excitation and collection through the fiber. Therefore, we performed multiphoton imaging on endoscopy-compatible 1 m and 3 m lengths of fiber in the back-scattered geometry, wherein the signals were collected either directly (non-descanned detection) or through the fiber (descanned detection). Second harmonic images were collected from barium titanate crystals as well as from biological samples (mouse tail tendon). In non-descanned detection conditions, the ARFs outperformed the SCF by up to 10 times in terms of signal-to-noise ratio of images. Significantly, only the DC-ARF, due to its high numerical aperture (NA) of 0.45 and wide-collection bandwidth (>1 µm), could provide images in the de-scanned detection configuration desirable for endoscopy. Thus, our systematic characterization and comparison of different optical fibers under different image collection configurations, confirms and establishes the utility of DC-ARFs for high-performing label-free multiphoton imaging-based micro-endoscopy.

Investigating the Association between Aortic Arch Variants and Intracranial Aneurysms.

BACKGROUND: There is an association between anterior cerebral artery vessel asymmetry and anterior communicating artery aneurysm, presumably based on flow dynamics. The purpose of this study is to investigate the potential relationship between aortic arch branching patterns and incidence of intracranial aneurysm. METHODS: This study included patients scanned over 1 year at our tertiary care center who underwent high-resolution imaging (computed tomography angiography or digital subtracted angiogram) of the head and neck arteries, aortic arch, and superior mediastinum. Exclusion criteria included patients with suboptimal images. Patient age, gender, aortic arch branching pattern, and the presence, location, and number of aneurysms were documented. RESULTS: Among the 1082 patients analyzed, 250 (23%) patients had a variant aortic arch branching pattern, 22 (8.8%) of whom had aneurysms. There were 104 patients with 126 aneurysms, with majority of patients with normal aortic arch branching pattern (n = 82, 79%). The most common variant was a common origin of the left common carotid artery and brachiocephalic trunk with or without direct origin of the left vertebral artery. Twenty-two patients with aneurysms had an aberrant aortic arch (21%), compared to 232 patients without an aneurysm (24%). Fischer exact test showed no statistically significant difference between the incidence of aneurysm with different aortic arch variant groups (two-tailed p-value = 0.715). CONCLUSION: To our knowledge, this is the first study to examine the association between aortic arch branching patterns and incidence of intracranial aneurysm. No significant association was found between aortic arch branching pattern and the incidence of intracranial aneurysm.

Mechanisms of SARS-CoV-2 Inactivation Using UVC Laser Radiation.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has had a tremendous impact on humanity. Prevention of transmission by disinfection of surfaces and aerosols through a chemical-free method is highly desirable. Ultraviolet C (UVC) light is uniquely positioned to achieve inactivation of pathogens. We report the inactivation of SARS-CoV-2 virus by UVC radiation and explore its mechanisms. A dose of 50 mJ/cm2 using a UVC laser at 266 nm achieved an inactivation efficiency of 99.89%, while infectious virions were undetectable at 75 mJ/cm2 indicating >99.99% inactivation. Infection by SARS-CoV-2 involves viral entry mediated by the spike glycoprotein (S), and viral reproduction, reliant on translation of its genome. We demonstrate that UVC radiation damages ribonucleic acid (RNA) and provide in-depth characterization of UVC-induced damage of the S protein. We find that UVC severely impacts SARS-CoV- 2 spike protein's ability to bind human angiotensin-converting enzyme 2 (hACE2) and this correlates with loss of native protein conformation and aromatic amino acid integrity. This report has important implications for the design and development of rapid and effective disinfection systems against the SARS-CoV-2 virus and other pathogens.

Multiscale molecular profiling of pathological bone resolves sexually dimorphic control of extracellular matrix composition.

Collagen assembly during development is essential for successful matrix mineralisation, which determines bone quality and mechanocompetence. However, the biochemical and structural perturbations that drive pathological skeletal collagen configuration remain unclear. Deletion of vascular endothelial growth factor (VEGF; also known as VEGFA) in bone-forming osteoblasts (OBs) induces sex-specific alterations in extracellular matrix (ECM) conformation and mineralisation coupled to vascular changes, which are augmented in males. Whether this phenotypic dimorphism arises as a result of the divergent control of ECM composition and its subsequent arrangement is unknown and is the focus of this study. Herein, we used murine osteocalcin-specific Vegf knockout (OcnVEGFKO) and performed ex vivo multiscale analysis at the tibiofibular junction of both sexes. Label-free and non-destructive polarisation-resolved second-harmonic generation (p-SHG) microscopy revealed a reduction in collagen fibre number in males following the loss of VEGF, complemented by observable defects in matrix organisation by backscattered electron scanning electron microscopy. This was accompanied by localised divergence in collagen orientation, determined by p-SHG anisotropy measurements, as a result of OcnVEGFKO. Raman spectroscopy confirmed that the effect on collagen was linked to molecular dimorphic VEGF effects on collagen-specific proline and hydroxyproline, and collagen intra-strand stability, in addition to matrix carbonation and mineralisation. Vegf deletion in male and female murine OB cultures in vitro further highlighted divergence in genes regulating local ECM structure, including Adamts2, Spp1, Mmp9 and Lama1. Our results demonstrate the utility of macromolecular imaging and spectroscopic modalities for the detection of collagen arrangement and ECM composition in pathological bone. Linking the sex-specific genetic regulators to matrix signatures could be important for treatment of dimorphic bone disorders that clinically manifest in pathological nano- and macro-level disorganisation. This article has an associated First Person interview with the first author of the paper.

Superresolved polarization-enhanced second-harmonic generation for direct imaging of nanoscale changes in collagen architecture.

Superresolution (SR) optical microscopy has allowed the investigation of many biological structures below the diffraction limit; however, most of the techniques are hampered by the need for fluorescent labels. Nonlinear label-free techniques such as second-harmonic generation (SHG) provide structurally specific contrast without the addition of exogenous labels, allowing observation of unperturbed biological systems. We use the photonic nanojet (PNJ) phenomena to achieve SR-SHG. A resolution of ∼ λ / 6 with respect to the fundamental wavelength, that is, a ∼ 2.3 -fold improvement over conventional or diffraction-limited SHG under the same imaging conditions is achieved. Crucially we find that the polarization properties of excitation are maintained in a PNJ. This is observed in experiment and simulations. This may have widespread implications to increase sensitivity by detection of polarization-resolved SHG by observing anisotropy in signals. These new, to the best of our knowledge, findings allowed us to visualize biological SHG-active structures such as collagen at an unprecedented and previously unresolvable spatial scale. Moreover, we demonstrate that the use of an array of self-assembled high-index spheres overcomes the issue of a limited field of view for such a method, allowing PNJ-assisted SR-SHG to be used over a large area. Dysregulation of collagen at the nanoscale occurs in many diseases and is an underlying cause in diseases such as lung fibrosis. Here we demonstrate that pSR-SHG allows unprecedented observation of changes at the nanoscale that are invisible by conventional diffraction-limited SHG imaging. The ability to nondestructively image SHG-active biological structures without labels at the nanoscale with a relatively simple optical method heralds the promise of a new tool to understand biological phenomena and drive drug discovery.

Bilateral complete ureteral duplication with calculi obstructing both limbs of left double ureter.

INTRODUCTION: A woman with bilateral complete ureteral duplication with stones simultaneously obstructing both limbs of the left double ureter is presented. A search of the English medical literature suggests that this is the first reported case. Based on the initial difficulty accessing the stones via ureteroscopy we make recommendations regarding how this rare problem should be approached if encountered. PRESENTATION OF CASE: A 37-year old woman with left-sided flank pain was discovered on CT scan to have bilateral complete ureteral duplication and three stones obstructing both limbs of the left double ureter. Ureteroscopy was initially unsuccessful due to the very small calibre and unyielding nature of the ureters and both ureteral limbs were stented. Repeat ureteroscopy was easily achieved after pre-stenting and the impacted stones were completely cleared with intracorporeal laser lithotripsy. DISCUSSION: The smaller calibre of both double ureters and their presence in a common adventitial sheath distally, made initial attempts at ureteroscopy difficult. Stenting both limbs increased ureteral compliance, passively dilated both ureters and allowed for improved manoeuvrability and retrograde passage of the ureteroscope. Based on the experience with this first reported case it is recommended that pre-stenting should be routinely performed prior to any attempt at ureteroscopy in cases of stones complicating completely duplicated ureters. CONCLUSION: We report the first recorded case of bilateral complete ureteral duplication with stones simultaneously obstructing both limbs of the double ureter and recommend that routine pre-stenting be done prior to ureteroscopy to allow easy uncomplicated retrograde passage of the ureteroscope.

A case of neurosarcoidosis with labyrinthine involvement.

Sarcoidosis is a chronic granulomatous disease of unknown aetiology, which may involve any organ system. It most commonly occurs in adults with childhood involvement being rare. Central nervous system involvement is seen in up to 25% and typically involves meningeal disease resulting in multiple cranial neuropathies. Other common clinical findings include seizures, headache, dementia, and pituitary dysfunction. Imaging plays a central role in the diagnosis with typical findings including pachymeningeal and leptomeningeal enhancing lesions. Other imaging findings include lacunar and major territory infarcts, hypothalamic and infundibular thickening, hydrocephalus, and cranial nerve enhancement. We present a case of an eight-year-old male patient with progressive headache, visual disturbance, unilateral sensory hearing loss, and multiple cranial neuropathies. Imaging findings demonstrated the classic pachymeningeal and leptomeningeal enhancement along much of the skull base, as well as enhancement of the right and left second and eighth cranial nerves. Extensive inflammatory changes were noted in the temporal bones and paranasal sinuses. There was also enhancement of the right and left labyrinths. Sinus biopsy confirmed sarcoidosis. We present the first case to our knowledge of sarcoid labyrinthitis.

Overcoming obstacles to establish a multidisciplinary team approach to hepatobiliary diseases: a working model in a Caribbean setting.

INTRODUCTION: By providing a structured forum to exchange information and ideas, multidisciplinary team meetings improve working relationships, expedite investigations, promote evidence-based treatment, and ultimately improve clinical outcomes. METHODS: This discursive paper reports the introduction of a multidisciplinary team approach to manage hepatobiliary diseases in Jamaica, focusing on the challenges encountered and the methods used to overcome these obstacles. CONCLUSION: Despite multiple challenges in resource-limited environments, a multidisciplinary team approach can be incorporated into clinical practice in developing nations. Policy makers should make it a priority to support clinical, operational, and governance aspects of the multidisciplinary teams.

Non-surgical pneumoperitoneum after oro-genital intercourse.

INTRODUCTION: In many cases, a pneumoperitoneum is due to air escaping from a perforated hollow viscus or surgical intervention but there are increasing reports of non-surgical causes. PRESENTATION OF CASE: We report a case where a pneumoperitoneum was identified after oro-genital sexual intercourse. DISCUSSION: There were nineteen reported cases of non-surgical pneumoperitoneum from gynaecologic causes up to May 2013. We report an additional case four hours after oro-genital intercourse. Close clinical observation and symptomatic treatment are usually all that is required but operative interventions should be considered if the patient develops abdominal pain, peritoneal signs, fever or leukocytosis during observation. CONCLUSION: This adds to the world literature on non-surgical pneumoperitoneum from oro-genital intercourse. Clinicians should be aware of this condition and focus on medical-sexual history as this information could prevent a patient from being exposed to expensive diagnostics and invasive operative treatments. Patients should also be educated about the mechanisms to avoid future possible diagnostic dilemmas.

Endoscopic transmural drainage of pancreatic pseudocysts: technical challenges in the resource poor setting.

Although surgical drainage of pancreatic pseudocysts has been superseded by less invasive options, the requirement for specialized equipment, technical expertise, and consumables limits the options available in low resource settings. We describe the challenges experienced during endoscopic transmural drainage in a low resource setting and the methods used to overcome these barriers. Despite operating in a low resource environment, endoscopic drainage of pancreatic pseudocysts can be incorporated into our armamentarium with minimal change to the existing hardware. Careful patient selection by a dedicated multidisciplinary team should be observed in order to achieve good outcomes.

Laparoscopic Inguinal Hernia Repair in a Developing Nation: Short-term Outcomes in 103 Consecutive Procedures.

BACKGROUND: There are no published data on the outcomes of inguinal hernia repair from the Anglophone Caribbean. To the best of our knowledge, this is the first report of a series of laparoscopic inguinal hernia repairs from the region. MATERIALS AND METHODS: Data was extracted from a prospectively maintained database of consecutive trans abdominal pre-peritoneal (TAPP) repairs done between June 1, 2005 and May 30, 2012. Perioperative data collected included patient demographics, hernia type, operative technique, duration of surgery, intra-operative details, morbidity, analgesia requirements, and duration of hospitalization. A telephone survey was also performed to identify late recurrences and complications. Descriptive statistics were generated using Statistical Package for Social Sciences (SPSS) Ver 12.0. RESULTS: There were 103 consecutive TAPP procedures in 88 patients at an average age of 35.4 years ± 12.9 (standard deviation; SD) and average body mass index (BMI) of 28.9 Kg/m(2) ± 2.23 (SD). The indications were bilateral (30), recurrent unilateral (24), and primary unilateral (49) inguinal hernias. The mean duration of operation was 68.5 minutes (SD ± 10.4; Range: 55-95; Median 65; Mode 65) minutes for unilateral TAPP and 89 minutes (SD ± 7.61; Range: 80-105; Median 90; Mode 90) for bilateral repairs. Post-operatively, 65/70 patients required ≤1 dose of parenteral opioid analgesia and 74 (84.1%) patients discontinued oral analgesia within 48 hours of operation. Complications were recorded in six (5.8%) cases and a recurrence in one (0.97%) case after a mean follow-up period of 3.2 years (SD ± 1.8; Range: 0.5-7). CONCLUSION: Laparoscopic inguinal hernia repair is a safe and effective operation in this setting.

Vascular supply to the liver: a report of a rare arterial variant.

In the classic description of hepatic arterial supply, the common hepatic artery originates from the coeliac trunk. However, there are numerous variations to this classic pattern. We report a rare variant pattern of hepatic arterial supply and discuss the clinical significance of this variation.

Accessory renal arteries in a Caribbean population: a computed tomography based study.

INTRODUCTION: The commonest variation to the classic anatomic description of renal arterial supply is the presence of accessory renal arteries. The incidence varies widely according to ethnicity. There is no data on the prevalence of these anomalies in persons of Caribbean ethnicity. METHODS: All CT scans done over two years from July 1, 2010 to June 30, 2012 were retrospectively evaluated. The anatomy of the renal arterial supply was reported from these studies and the anatomy of accessory renal arteries was documented. RESULTS: There were 302 CT scans evaluated and accessory renal arteries were present in 109/302 (36.1%) CT scans, 95% confidence interval 30.6%, 41.4%. There were 71/309 (23.5%) patients with accessory arteries on the left and 54/309 (17.9%) had them on the right (p 0.087). Of these, 16 (14.7%) patients had bilateral accessory renal arteries present. The most common origin for the accessory arteries was the abdominal aorta in 108 (99.1%) cases and in 1 case the accessory artery arose from the coeliac trunk. There were 80 left sided accessory renal arteries: 17 (21.3%) upper polar and 27 (33.8%) lower polar arteries. Of 62 right sided accessory arteries, 14 (22.6%) were upper polar and 26 (42%) were lower polar arteries. CONCLUSION: This is the first population-based report of anatomic anomalies in renal arterial supply in a Caribbean population. These are important findings that may affect vascular and urologic procedures on persons of Caribbean ethnicity.