Ambulatory Detection of Isolated Rapid-Eye-Movement Sleep Behavior Disorder Combining Actigraphy and Questionnaire.

BACKGROUND: Isolated rapid-eye-movement sleep behavior disorder (iRBD) is in most cases a prodrome of neurodegenerative synucleinopathies, affecting 1% to 2% of middle-aged and older adults; however, accurate ambulatory diagnostic methods are not available. Questionnaires lack specificity in nonclinical populations. Wrist actigraphy can detect characteristic features in individuals with RBD; however, high-frequency actigraphy has been rarely used. OBJECTIVE: The aim was to develop a machine learning classifier using high-frequency (1-second resolution) actigraphy and a short patient survey for detecting iRBD with high accuracy and precision. METHODS: The method involved analysis of home actigraphy data (for seven nights and more) and a nine-item questionnaire (RBD Innsbruck inventory and three synucleinopathy prodromes of subjective hyposmia, constipation, and orthostatic dizziness) in a data set comprising 42 patients with iRBD, 21 sleep clinic patients with other sleep disorders, and 21 community controls. RESULTS: The actigraphy classifier achieved 95.2% (95% confidence interval [CI]: 88.3-98.7) sensitivity and 90.9% (95% CI: 82.1-95.8) precision. The questionnaire classifier achieved 90.6% accuracy and 92.7% precision, exceeding the performance of the Innsbruck RBD Inventory and prodromal questionnaire alone. Concordant predictions between actigraphy and questionnaire reached a specificity and precision of 100% (95% CI: 95.7-100.0) with 88.1% sensitivity (95% CI: 79.2-94.1) and outperformed any combination of actigraphy and a single question on RBD or prodromal symptoms. CONCLUSIONS: Actigraphy detected iRBD with high accuracy in a mixed clinical and community cohort. This cost-effective fully remote procedure can be used to diagnose iRBD in specialty outpatient settings and has potential for large-scale screening of iRBD in the general population. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The Influence of Patterned Surface Features on the Accumulation of Bovine Synovial Fluid-Induced Aggregates of Staphylococcus aureus.

Periprosthetic joint infection (PJI) after joint replacement is a major clinical issue requiring multiple surgeries and antibiotic interventions. Recent in vitro research has shown that PJI staphylococcal strains rapidly form antibiotic-resistant free-floating aggregates in the presence of bovine synovial fluid (BSF). Staphylococcal aggregates are also present in human PJI joint fluid. However, the influence of surface roughness and fluid shear on the attachment and retention of such aggregates on surfaces is not known. Our aim was to assess how surface roughness and fluid shear stress influenced the attachment and retention of Staphylococcus aureus BSF-mediated aggregates on smooth- and rough-patterned titanium in flow cells compared to nonaggregated cells. The attachment of S. aureus aggregates was significantly greater than that of single cells but was independent of surface roughness; however, on the patterned surfaces, aggregates preferentially accumulated in the grooves. Fibrous components in the BSF were also colocalized with the grooves. After a 24-h attachment-and-incubation period, different shear stresses were applied. There was significant detachment from flat surfaces at a flow rate of 1 mL/min (τw = 0.0012 Pa) but minimal detachment from the patterned surfaces, even at flow rates as high as 13.9 mL/min (τw = 0.0169 Pa). The retention of bacterial aggregates and biofilms on rough surfaces exposed to shear might be an important consideration for the location of colonization on orthopedic implants, which can have wide ranges of roughness and surface features and can influence the efficacy of shear-based debridement methods such as pulse lavage. IMPORTANCE Periprosthetic joint infections occurring after joint replacement are a major clinical problem requiring repeated surgeries and antibiotic interventions. Staphylococcus aureus is the most prominent bacterium causing most implant-related infections. S. aureus can form a biofilm, which is defined as a group of attached bacteria with the formation of an envelope that is resistant to antibiotics. The attachment and retention of these bacteria on implant surfaces are not clearly understood. Recent in vitro research investigations have shown that staphylococcal strains rapidly form aggregates in the presence of bovine synovial fluid (BSF) in the joints, which allows bacteria time to attach to the implant surface, leading to biofilm formation. Thus, in this study, we examined the attachment of aggregates on titanium surfaces with varying roughnesses and found robust bacterial attachment and retention along the ridges and grooves, which colocalized with the deposition of fibrous components present in the BSF.

Spexin modulates molecular thermogenic profile of adipose tissue and thermoregulatory behaviors in female C57BL/6 mice.

Thermoregulation is the physiological process by which an animal regulates body temperature in response to its environment. It is known that galanin, a neuropeptide widely distributed throughout the central nervous system and secreted by the gut, plays a role in thermoregulatory behaviors and metabolism. We tested the ability of the novel neuropeptide spexin, which shares sequence homology to galanin, to regulate these functions in female mice. Supraphysiological levels of spexin in C57BL/6 mice did not lead to weight loss after 50 days of treatment. Behavioral analysis of long-term spexin treatment showed it decreased anxiety and increased thermoregulatory nest building, which was not observed when mice were housed at thermoneutral temperatures. Treatment also disrupted the thermogenic profile of brown and white adipose tissue, decreasing mRNA expression of Ucp1 in BAT and immunodetection of ß3-adrenergic receptors in gWAT. Our results reveal novel functions for spexin as a modulator of thermoregulatory behaviors and adipose tissue metabolism.

Staphylococcus aureus Aggregates on Orthopedic Materials under Varying Levels of Shear Stress.

Periprosthetic joint infection (PJI) occurring after artificial joint replacement is a major clinical issue requiring multiple surgeries and antibiotic interventions. Staphylococcus aureus is the bacterium most commonly responsible for PJI. Recent in vitro research has shown that staphylococcal strains rapidly form aggregates in the presence of synovial fluid (SF). We hypothesize that these aggregates provide early protection to bacteria entering the wound site, allowing them time to attach to the implant surface, leading to biofilm formation. Thus, understanding the attachment kinetics of these aggregates is critical in understanding their adhesion to various biomaterial surfaces. In this study, the number, size, and surface area coverage of aggregates as well as of single cells of S. aureus were quantified under various conditions on different orthopedic materials relevant to orthopedic surgery: stainless steel (316L), titanium (Ti), hydroxyapatite (HA), and polyethylene (PE). It was observed that, regardless of the material type, SF-induced aggregation resulted in reduced aggregate surface attachment and greater aggregate size than the single-cell populations under various shear stresses. Additionally, the surface area coverage of bacterial aggregates on PE was relatively high compared to that on other materials, which could potentially be due to the rougher surface of PE. Furthermore, increasing shear stress to 78 mPa decreased aggregate attachment to Ti and HA while increasing the aggregates' average size. Therefore, this study demonstrates that SF induced inhibition of aggregate attachment to all materials, suggesting that biofilm formation is initiated by lodging of aggregates on the surface features of implants and host tissues.IMPORTANCE Periprosthetic joint infection occurring after artificial joint replacement is a major clinical issue that require repeated surgeries and antibiotic interventions. Unfortunately, 26% of patients die within 5 years of developing these infections. Staphylococcus aureus is the bacterium most commonly responsible for this problem and can form biofilms to provide protection from antibiotics as well as the immune system. Although biofilms are evident on the infected implants, it is unclear how these are attached to the surface in the first place. Recent in vitro investigations have shown that staphylococcal strains rapidly form aggregates in the presence of synovial fluid and provide protection to bacteria, thus allowing them time to attach to the implant surface, leading to biofilm formation. In this study, we investigated the attachment kinetics of Staphylococcus aureus aggregates on different orthopedic materials. The information presented in this article will be useful in surgical management and implant design.

High Altitude Head and Neck Paragangliomas: A First Sub-Himalayan Experience.

Objectives: High-altitude natives have a high incidence of parangangliomas (PGL) of the head and neck, especially the carotid body tumor. The aim of this study is to describe the clinical presentation, pattern, altitude of residence, distribution, management, and follow-up of head and neck paragangliomas (HNPGL) in our sub-Himalayan population. Study Design: Retrospective cohort study. Setting: Academic tertiary care hospital. Methods: Hospital records of 20 patients of HNPGL diagnosed from December 2017 to December 2021 were retrieved for analysis. Results: Twenty patients with 23 HNPGL, with a mean age of 41.74 years were managed in our institute. The female-to-male ratio was 2.3: 1 and the mean follow-up was 29.95 months. Nine had carotid body (CBPGL), 7 had tympanic (TPGL), 2 had jugular (JPGL), and 2 had vagal paragangliomas (VPGL). Multiple PGL were seen in 4 patients (20%). Majority of cases (all CBPGL and 57.14% of TPGL) were residents of the high altitude, and the rest were from the low altitude. Fifteen patients (8 CBPGL, 7 TPGL) were operated. There were no major complications except in a patient with large carotid body tumor required anastomosis of carotid artery. Five patients received stereotactic radiotherapy, and 1 malignant PGL received chemoradiotherapy. Conclusion: In this study, JPGL and VPGL are common at low altitudes, whereas carotid body and tympanic PGL were the most common tumor at high altitudes. Being a retrospective and study small sample size, a definite conclusion is not established, however, a genetic analysis and inclusion of a wider population in a future prospective study may establish the hypothesis.

Killing of a Multispecies Biofilm Using Gram-Negative and Gram-Positive Targeted Antibiotic Released from High Purity Calcium Sulfate Beads.

BACKGROUND: Multispecies biofilm orthopedic infections are more challenging to treat than mono-species infections. In this in-vitro study, we aimed to determine if a multispecies biofilm, consisting of Gram positive and negative species with different antibiotic susceptibilities could be treated more effectively using high purity antibiotic-loaded calcium sulfate beads (HP-ALCSB) containing vancomycin (VAN) and tobramycin (TOB) in combination than alone. METHODS: Three sets of species pairs from bioluminescent strains of Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) and clinical isolates, Enterococcus faecalis (EF) and Enterobacter cloacae were screened for compatibility. PA + EF developed intermixed biofilms with similar cell concentrations and so were grown on 316L stainless steel coupons for 72 h or as 24 h agar lawn biofilms and then treated with HP-ALCSBs with single or combination antibiotics and assessed by viable count or bioluminescence and light imaging to distinguish each species. Replica plating was used to assess viability. RESULTS: The VAN + TOB bead significantly reduced the PA + EF biofilm CFU and reduced the concentration of surviving antibiotic tolerant variants by 50% compared to single antibiotics. CONCLUSIONS: The combination of Gram-negative and positive targeted antibiotics released from HP-ALCSBs may be more effective in treating multispecies biofilms than monotherapy alone.

Botulinum Toxin Type A Immunogenicity across Multiple Indications: An Overview Systematic Review.

BACKGROUND: Botulinum toxin type A has been used to treat a wide array of neurologic, medical, and aesthetic indications. Several factors contribute to the formation of neutralizing antibodies, such as shorter intervals of treatment, higher dosage, amounts of antigenic proteins, serotypes, and storage of formulations. METHOD: This overview followed the Cochrane guideline for overview reviews. The AMSTAR-2 (revised version of A Measurement Tool to Assess Systematic Reviews) tool was used for the critical appraisal of the selected systematic reviews. RESULTS: Five systematic reviews consisting of 203 studies (17,815 patients) were included, and their AMSTAR-2 scores were low to critically poor. There was high heterogeneity between the studies. Across the clinical indications, neutralizing antibody prevalence was significantly higher in dystonia, spasticity, and urologic conditions, and nil to insignificant in hyperhidrosis and aesthetic indications. The overall rate for the neutralizing antibody formation across three different formulations, abobotulinumtoxinA, incobotulinumtoxinA, and onabotulinumtoxinA, was 1 to 2.1 percent, with no significant difference between them. RESULTS: Although there is debate on the prevalence rate across the different botulinum toxin type A formulations in individual systematic reviews, the overall frequency of the development of neutralizing antibodies and the immunogenicity of abobotulinumtoxinA, incobotulinumtoxinA, and onabotulinumtoxinA remain low to insignificant. CONCLUSIONS: Properly designed comparative trials are required to explore the difference in the prevalence of neutralizing antibodies across the commercially available botulinum toxin type A products. Such studies should also examine the relevance of neutralizing antibody titer to clinical responsiveness and nonresponse.

Mapping Bacterial Biofilm on Features of Orthopedic Implants In Vitro.

Implant-associated infection is a major complication of orthopedic surgery. One of the most common organisms identified in periprosthetic joint infections is Staphylococcus aureus, a biofilm-forming pathogen. Orthopedic implants are composed of a variety of materials, such as titanium, polyethylene and stainless steel, which are at risk for colonization by bacterial biofilms. Little is known about how larger surface features of orthopedic hardware (such as ridges, holes, edges, etc.) influence biofilm formation and attachment. To study how biofilms might form on actual components, we submerged multiple orthopedic implants of various shapes, sizes, roughness and material type in brain heart infusion broth inoculated with Staphylococcus aureus SAP231, a bioluminescent USA300 strain. Implants were incubated for 72 h with daily media exchanges. After incubation, implants were imaged using an in vitro imaging system (IVIS) and the metabolic signal produced by biofilms was quantified by image analysis. Scanning electron microscopy was then used to image different areas of the implants to complement the IVIS imaging. Rough surfaces had the greatest luminescence compared to edges or smooth surfaces on a single implant and across all implants when the images were merged. The luminescence of edges was also significantly greater than smooth surfaces. These data suggest implant roughness, as well as large-scale surface features, may be at greater risk of biofilm colonization.

Free-Floating Aggregate and Single-Cell-Initiated Biofilms of Staphylococcus aureus.

Periprosthetic joint infection (PJI) occurring after artificial joint replacement is a major clinical issue requiring multiple surgeries and antibiotic interventions. Staphylococcus aureus is the common bacteria responsible for PJI. Recent in vitro research has shown that staphylococcal strains rapidly form free-floating aggregates in the presence of synovial fluid (SF) with biofilm-like resistance to antimicrobial agents. However, the development of biofilms formed from these aggregates under shear have not been widely investigated. Thus, in this study, we examined the progression of attached biofilms from free-floating aggregates. Biofilms were grown for 24 h in flow cells on titanium discs after inoculation with either pre-aggregated or single planktonic cells. Image analysis showed no significant difference between the biofilm formed from aggregates vs. the planktonic cells in terms of biomass, surface area, and thickness. Regarding antibiotic susceptibility, there were 1 and 2 log reductions in biofilms formed from single cells and aggregates, respectively, when treated with vancomycin for 24 h. Thus, this study demonstrates the formation of biofilm from free-floating aggregates and follows a similar developmental time period and shows similar antibiotic tolerance to more traditionally inoculated in vitro flow cell biofilms.

Biomimetic Microfluidic Platforms for the Assessment of Breast Cancer Metastasis.

Of around half a million women dying of breast cancer each year, more than 90% die due to metastasis. Models necessary to understand the metastatic process, particularly breast cancer cell extravasation and colonization, are currently limited and urgently needed to develop therapeutic interventions necessary to prevent breast cancer metastasis. Microfluidic approaches aim to reconstitute functional units of organs that cannot be modeled easily in traditional cell culture or animal studies by reproducing vascular networks and parenchyma on a chip in a three-dimensional, physiologically relevant in vitro system. In recent years, microfluidics models utilizing innovative biomaterials and micro-engineering technologies have shown great potential in our effort of mechanistic understanding of the breast cancer metastasis cascade by providing 3D constructs that can mimic in vivo cellular microenvironment and the ability to visualize and monitor cellular interactions in real-time. In this review, we will provide readers with a detailed discussion on the application of the most up-to-date, state-of-the-art microfluidics-based breast cancer models, with a special focus on their application in the engineering approaches to recapitulate the metastasis process, including invasion, intravasation, extravasation, breast cancer metastasis organotropism, and metastasis niche formation.

Mobilization of human CD34+ CD133+ and CD34+ CD133(-) stem cells in vivo by consumption of an extract from Aphanizomenon flos-aquae--related to modulation of CXCR4 expression by an L-selectin ligand?

OBJECTIVE: The goal of this study was to evaluate effects on human stem cells in vitro and in vivo of an extract from the edible cyanobacterium Aphanizomenon flos-aquae (AFA) enriched for a novel ligand for human CD62L (L-selectin). EXPERIMENTAL APPROACH: Ligands for CD62L provide a mechanism for stem cell mobilization in conjunction with down-regulation of the CXCR4 chemokine receptor for stromal derived factor 1. Affinity immunoprecipitation was used to identify a novel ligand for CD62L from a water extract from AFA. The effects of AFA water extract on CD62L binding and CXCR4 expression was tested in vitro using human bone marrow CD34+ cells and the two progenitor cell lines, KG1a and K562. A double-blind randomized crossover study involving 12 healthy subjects evaluated the effects of consumption on stem cell mobilization in vivo. RESULTS: An AFA extract rich in the CD62L ligand reduced the fucoidan-mediated externalization of the CXCR4 chemokine receptor on bone marrow CD34+ cells by 30% and the CD62L+ CD34+ cell line KG1A by 50% but did not alter the CXCR4 expression levels on the CD34(-) cell line K562. A transient, 18% increase in numbers of circulating CD34+ stem cells maximized 1 hour after consumption (P<.0003). When 3 noncompliant volunteers were removed from analysis, the increase in CD34+ cells was 25% (P<.0001). CONCLUSION: AFA water extract contains a novel ligand for CD62L. It modulates CXCR4 expression on CD34+ bone marrow cells in vitro and triggers the mobilization of CD34+ CD133+ and CD34+ CD133(-) cells in vivo.

The First Case Report of Robotic Multivisceral Resection for Synchronous Liver Metastasis from Pancreatic Neuroendocrine Tumor: A Case Report and Literature Review.

INTRODUCTION: Surgery for liver metastases in pancreatic neuroendocrine tumor (PNET) improves overall survival rate. We present the first case report for robotic multivisceral resection of distal pancreas, spleen, and left liver for metastatic PNET. MATERIALS AND METHODS: We present a case of 52-year-old female diagnosed with PNET in the pancreatic neck metastatic to the liver, responding to somatostatin and bland embolization, who underwent surgical debulking using da Vinci robotic platform. Intraoperative Doppler ultrasound was used to define the vascular distribution and tumor extension. The parenchymal liver transection was performed with vessel sealer. The distal pancreas and the spleen were approached medial to lateral and resected in an en-bloc fashion. The left liver inflow, outflow, and splenic artery and vein were transected with vascular stapler device. RESULTS: Da Vinci robot-assisted multivisceral resection has been performed with good postoperative outcome. Operative time was 369 minutes and the estimated blood loss was 100 mL. The patient had a short hospital stay with quick recovery and good outcome at 5 months follow-up after the surgery. DISCUSSION: Liver metastases in PNETs are considered an adverse factor. Aggressive surgical management is a mainstay. The laparoscopic approach to pancreatic or hepatic surgery is difficult in inexperienced hands with steep learning curve. The recent robotic system seems to overcome many limitations. This is the first case of robotic multivisceral resection for synchronous liver metastasis from PNET. Concurrent primary tumor resection with hepatectomy offers potential curative intention.

Gemcitabine-induced pulmonary toxicity: case report and review of the literature.

Gemcitabine is a pyrimidine analog with a similar chemical structure and mechanism of action, as cytarabine. It has been shown to be a highly active agent for non-small cell lung cancer, pancreatic cancer, urothelial cancer, breast cancer and ovarian cancer. Gemcitabine is relatively well tolerated and myelosuppression is the dose-limiting toxicity. Pulmonary toxicity with gemcitabine is relatively uncommon, but a well recognized entity, associated with significant morbidity and mortality. A high index of suspicion, early diagnosis and timely intervention with oxygen supplementation, steroids, and diuretics is necessary to manage patients with this complication.

Fast Disintegrating Combination Tablet of Taste Masked Levocetrizine Dihydrochloride and Montelukast Sodium: Formulation Design, Development, and Characterization.

The aim of this study was to prepare fast disintegrating combination tablet of taste masked Levocetrizine dihydrochloride and Montelukast sodium by using direct compression method. To prevent bitter taste and unacceptable odour of the Levocetrizine dihydrochloride drug, the drug was taste masked with ion exchange resins like Kyron-T-104 and Tulsion-412. Among the two resins, Kyron-T-104 was selected for further studies because of high drug loading capacity, low cost, and better drug release profile. An ion exchange resin complex was prepared by the batch technique and various parameters; namely, resin activation, drug: resin ratio, pH, temperature, and stirring time, and swelling time were optimized to successfully formulate the tasteless drug resin complex (DRC). The tablets were prepared using microcrystalline cellulose (MCC) PH 102 as diluent along with crospovidone (CP), croscarmellose sodium (CCM), and sodium starch glycolate (SSG) as a superdisintegrants. The tablets were evaluated for weight variation, hardness, friability, wetting time, water absorption ratio, disintegration time (DT), and dissolution study and it was concluded that the tablet formulation prepared with 2% SSG + CCS showed better disintegration time in comparison with other formulation and good drug release. The stability studies were carried out for the optimized batch for three months and it showed acceptable results.

Effects of varying intraperitoneal pressure on liver function tests during laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy at standard-pressure pneumoperitoneum uses a pressure of 12-14 mm Hg, which may cause a variety of adverse physiological changes involving the respiratory, cardiovascular, and hepatorenal systems reflected as subclinical abnormalities in biochemical parameters. The use of low-pressure pneumoperitoneum in the range of 8-10 mm Hg has been shown to reduce the adverse physiological changes without affecting the outcome of surgery. SUBJECTS AND METHODS: This study was done in a randomized controlled manner. Patients with gallstone disease (n=101) underwent laparoscopic cholecystectomy. Patients were randomly assigned to high-pressure laparoscopic cholecystectomy (HPLC) (n=51) and low-pressure laparoscopic cholecystectomy (LPLC) (n=50) and underwent surgery at pressures of 14 mm Hg and 8 mm Hg, respectively. Liver function tests, including total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase, were obtained preoperatively and on postoperative Days 1 and 7. RESULTS: The two study groups had similar demographic profiles, and there were no significant differences in the operative time (HPLC, 47.25 ± 6.73 minutes; LPLC, 48.00 ± 7.76 minutes; P=.6071) and pneumoperitoneum time (HPLC, 34.02 ± 5.29 minutes; LPLC, 34.60 ± 6.13 minutes; P=.6115). On postoperative Day 1, the total bilirubin levels were 1.0684 ± 0.4108 mg/dL and 0.8926 ± 0.3162 mg/dL for HPLC and LPLC (P=.0179), respectively, AST levels were 66.0810 ± 25.5868 IU/L and 42.2420 ± 14.7301 IU/L (P=.0001), respectively, and ALT levels were 68.1410 ± 31.4572 IU/L and 42.7460 ± 17.9405 IU/L (P=.0001), respectively. Thus, liver enzyme activities were significantly elevated in the HPLC group compared with the LPLC group. CONCLUSIONS: LPLC causes less abnormality in liver function tests in the postoperative period compared with HPLC. LPLC should be considered in all patients undergoing laparoscopic cholecystectomy, especially those patients with compromised liver functions.