Bizarre parosteal osteochondromatous proliferation in the distal ulna where the lesion is continuous with the medullary cavity: a case report.

BACKGROUND: Bizarre parosteal osteochondromatous proliferation (BPOP) is a rare benign bone tumor, it is also called "Nora's lesion". The lesion is characterized by heterotopic ossification of the normal bone cortex or parosteal bone. The etiology of BPOP is unclear and may be related to trauma. In most BPOPs, the lesion is not connected to the medullary cavity. Here we report an atypical case, characterized by reversed features compared to the typical BPOP, which demonstrated continuity of the lesion with the cavity. CASE PRESENTATION: An 11-year-old female child had a slow-growing mass on her right wrist for 8 months with forearm rotation dysfunction. Plain X-rays showed an irregular calcified mass on the right distal ulna, and computed tomography (CT) showed a pedunculated mass resembling a mushroom protruding into the soft tissue at the distal ulna. The medulla of this lesion is continuous with the medulla of the ulna. A surgical resection of the lesion, together with a portion of the ulnar bone cortex below the tumor was performed, and the final pathology confirmed BPOP. After the surgery, the child's forearm rotation function improved significantly, and there was no sign of a recurrence at 1-year follow-up. CONCLUSION: It is scarce for BPOP lesions to communicate with the medullary cavity. However, under-recognition of these rare cases may result in misdiagnosis or inappropriate treatment thereby increasing the risk of recurrence. Therefore, special cases where BPOP lesions are continuous with the medulla are even more important to be studied to understand better and master these lesions. Although BPOP is a benign tumor with no evidence of malignant transformation, the recurrence rate of surgical resection is high. We considered the possibility of this particular disease prior to surgery and performed a surgical resection with adequate safety margins. Regular postoperative follow-up is of utmost importance, without a doubt.

Bizarre parosteal osteochondromatous proliferation (Nora lesion) involving the spine: a case report and systematic review.

Bizarre parosteal osteochondromatous proliferation (BPOP), also termed Nora lesion, is a rare, benign tumor most often located in the hands and feet. We herein present the second reported case of BPOP affecting the spine, an uncommon location. One year after surgical excision, the patient was pain-free and showed no evidence of recurrence. We reviewed a total of 323 cases of BPOP among 101 articles, providing the first systematic update on the latest knowledge of BPOP. The age of patients with BPOP ranges from 3 months to 87 years, peaking in the second and third decades of life. The hands are the most common location of BPOP (58.39%), followed by the feet (20.81%). Imaging features play a key role in the diagnosis of BPOP, but histopathologic diagnosis remains the gold standard. Differential diagnosis of BPOP should be based on the epidemiologic and clinical features as well as clinical examination findings. Surgical resection is the most extensively used treatment for BPOP. Recurrence is common (37.44%) and can be treated with re-excision. This article can deepen our understanding of BPOP and will be helpful for the diagnosis and treatment of BPOP in clinical practice.

A unique presentation of the rare Nora's lesion, symptomatic bizarre parosteal osteochondromatous proliferation: A case report.

Bizarre parosteal osteochondromatous proliferations, also known as Nora's lesions, are rare benign tumors with a high recurrence rate. They are often difficult to identify because of their similar appearance to other tumors. We describe a 25-year-old healthy female patient with bizarre parosteal osteochondromatous proliferations in an uncommon location on the pelvic ilium, presenting with unique clinical findings of abdominal pain and femoral paresthesia and showing atypical radiographic findings. To the best of our knowledge, this is one of the very few cases ever reported in the literature of Nora's lesion in this particular location and possibly the first case ever with this specific presentation. The lesions' radiographic images, combined orthopedic and general surgery procedures, and histological analysis are detailed. The patient's continued 4-year follow-up has demonstrated no symptoms or evidence of recurrence.

Expression of norA, norB and norC efflux pump genes mediating fluoroquinolones resistance in MRSA isolates.

INTRODUCTION: Although fluoroquinolones are used to treat methicillin-resistant Staphylococcus aureus (MRSA)-induced infections, acquisition of antibiotic resistance by bacteria has impaired their clinical relevance. We aimed to evaluate the frequency of norA, norB, and norC efflux pump genes-mediating fluoroquinolones resistance and measure their expression levels in MRSA isolates. METHODOLOGY: 126 S. aureus isolates were collected from different clinical samples of adult hospitalized patients and identified by conventional microbiological methods. MRSA was diagnosed by cefoxitin disc diffusion method and minimum inhibitory concentration (MIC) of ciprofloxacin by broth microdilution method. The expression levels of efflux pump genes were measured by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: 80 (63.5%) MRSA isolates were identified and showed high level of resistance to erythromycin (80%), gentamicin (75%), clindamycin (65%) and ciprofloxacin (60 %). norA, norB and norC were detected in 75%, 35% and 55% of the MRSA isolates respectively. norC was the most commonly overexpressed gene measured by qRT-PCR, occurring in 40% of MRSA isolates, followed by norA (35%) and norB (30%). The expression of these genes was significantly higher in ciprofloxacin-resistant than quantitative real-time PCR ciprofloxacin-sensitive MRSA isolates. CONCLUSIONS: This study showed high prevalence and overexpression of efflux pump genes among MRSA isolates which indicates the significant role of these genes in the development of multidrug resistance against antibiotics including fluoroquinolones.

Bizarre Parosteal Osteochondromatous Proliferation (Nora's Lesion) Affecting Carpal Bones of the Hand in a Middle-Aged Female: A Case Report.

A 45-year-old woman complained of left wrist pain and swelling for two years accompanied by limited dorsiflexion. Plain X-rays revealed an abnormal bony mass in the carpal bones, further evaluated using computed tomography and magnetic resonance imaging. Upon confirmation of the benign nature surgical excisional biopsy of the lesion, the histopathology confirmed the diagnosis of Bizarre parosteal osteochondromatous proliferation (BPOP). The patient has remained pain-free and actively involved in her routine for the past two years. BPOP, affecting the carpal bones of the hand, are exceptionally rare occurrence. Attentive preoperative evaluation helps in diagnosis and to initiate measures to avoid recurrence.

Bizarre parosteal osteochondromatous proliferations of the temporal region: a case report.

Bizarre parosteal osteochondromatous proliferations (BPOPs) are distinct clinical-pathological entities that demonstrate combinations of atypical-appearing osseous and chondromatous tissues. These lesions are usually reactive in nature. Histopathologically, 'bizarre' cartilage is a characteristic feature of this lesion. BPOPs usually represent slow-growing painless bony hard protuberances that arise from the surface of affected bone cortices, typically the metacarpals, metatarsals, and phalanges. The occurrence of these lesions in the skull and jaws is sporadic. This case report highlights the clinical presentation, histopathological characteristics, and management of BPOP arising from the supraorbital rim in a 61-year-old female patient.

Bizarre Parosteal Osteochondromatous Proliferation of the Hand: A Report of an Atypical Case and Current Concepts.

Bizarre parosteal osteochondromatous proliferation (BPOP), or Nora's lesion, is an unusual, benign, bony lesion often found in the tubular small bones of the hand and foot. In general, two characteristic radiological signs are used to diagnose the lesion, namely, (1) the absence of corticomedullar continuity and (2) BPOP developed from the parosteal surface of bones with an intact underlying cortex. Here, we present an atypical case of Nora's lesion of the proximal phalanx of the index finger, in which BPOP was diagnosed only histologically, with preoperative imaging examinations (X-ray and MRI) suggesting another lesion (enchondroma). Therefore, imaging (X-ray and MRI) alone may be inadequate to achieve the correct diagnosis of the lesion because many cartilaginous neoplasms may surround a broad range of lesions that mimic BPOP. Only histopathological evidence can confirm the correct diagnosis of the lesion.

Unraveling the ligand specificity and promiscuity of the Staphylococcus aureus NorA efflux pump: a computational study.

Staphylococcus aureus, a gram-positive bacterial pathogen, develops antibiotic resistance partly through enhanced activity of transmembrane multi-drug efflux pump proteins like NorA. Being a prominent member of the Major Facilitator Superfamily (MFS), NorA transports various small molecules including hydrophilic fluoroquinolone antibiotics across the cell membrane. Intriguingly, NorA is inhibited by a structurally diverse set of small molecule inhibitors as well, indicating a highly promiscuous ligand/inhibitor recognition. Our study aims to elucidate the structural facets of this promiscuity. Known NorA inhibitors were grouped into five clusters based on chemical class and docked into ligand binding pockets on NorA conformations generated via molecular dynamics simulations. We discovered that several key residues, such as I23, E222, and F303, are involved in inhibitor binding. Additionally, residues I244, T223, F303, and F140 were identified as prominent in interactions with specific ligand clusters. Our findings suggest that NorA's substrate binding site, encompassing residues aiding ligand recognition based on chemical nature, facilitates the recognition of chemically diverse ligands. This insight into NorA's structural promiscuity in ligand recognition not only enhances understanding of antibiotic resistance mechanisms in S. aureus but also sets the stage for the development of more effective efflux pump inhibitors, vital for combating multidrug resistance.Communicated by Ramaswamy H. Sarma.

Bizarre Parosteal Osteochondromatous Proliferation (Nora's Lesion) Of the Second Proximal Phalanx Encasing the Flexor Tendon of the Foot: A Case Report.

Introduction: Bizarre Parosteal Osteochondromatous Proliferation (BPOP) is a rare benign lesion commonly referred to as Nora's lesion. It typically affects adults in their 20s-30s. Due to its aggressive local invasion, it can be confused with some malignant tumors, including chondrosarcoma. Nora's lesion can be diagnosed radiographically, and its diagnosis is confirmed with an excisional biopsy. Case Report: A 40-year-old Bahraini male complained of swelling over the metatarsal head of the second digit, increasing in size over a year. He also complained of a reduced range of motion of the second toe and a pins-and-needles sensation affecting the entire toe. Plain X-ray, computed tomography, and magnetic resonance imaging were done, showing findings suggestive of bizarre parosteal osteochondromatous. The lesion was encasing the flexor tendon of the second digit. He was treated with surgical excision, and histopathology confirmed the diagnosis of BPOP. Conclusion: We report on a rare presentation of BPOP in the second proximal phalanx of a male in his 40 s. The patient underwent a wide local excision, and the diagnosis was confirmed with histopathology.

Rare Case of Bizarre Parosteal Osteochondromatous Proliferation of Foot.

Introduction: Nora's lesion or bizarre parosteal osteochondromatous proliferation (BPOP) is a rare, benign lesion of small bones of hands and feet in adults. It composed of differing amounts of cartilage, bone, and spindle cells and an unusual form of calcified cartilage so-called "blue bone". Case Report: A 23-year-old male presented with swelling at the lateral side of the fifth toe of his right foot, which was separated from the adjacent toe. Radiographs showed a mass arising from the proximal phalanx of the little toe, with no medullary and cortical continuity. Excisional biopsy of the mass was performed, and a histologic diagnosis of BPOP of bone (Nora's lesion) was made. Conclusion: This case presented with a cartilaginous cap around tumor which is suggestive for benign nature of this tumor with some histological variation from bizarre variant along with no recurrence which is unlikely seen in BPOP.

NorA efflux pump mediates Staphylococcus aureus response to Pseudomonas aeruginosa pyocyanin toxicity.

Endogenous transporters protect Staphylococcus aureus against antibiotics and also contribute to bacterial defense from environmental toxins. We evaluated the effect of overexpression of four efflux pumps, NorA, NorB, NorC, and Tet38, on S. aureus survival following exposure to pyocyanin (PYO) of Pseudomonas aeruginosa, using a well diffusion assay. We measured the PYO-created inhibition zone and found that only an overexpression of NorA reduced S. aureus susceptibility to pyocyanin killing. The MICPYO of the NorA overexpressor increased threefold compared to that of wild-type RN6390 and was reduced 2.5-fold with reserpine, suggesting that increased NorA efflux caused PYO resistance. The PYO-created inhibition zone of a ΔnorA mutant was consistently larger than that of a plasmid-borne NorA overexpressor. PYO also produced a modest increase in norA expression (1.8-fold at 0.25 µg/mL PYO) that gradually decreased with increasing PYO concentrations. Well diffusion assays carried out using P. aeruginosa showed that ΔnorA mutant was less susceptible to killing by PYO-deficient mutants PA14phzM and PA14phzS than to killing by PA14. NorA overexpression led to reduced killing by all tested P. aeruginosa. We evaluated the NorA-PYO interaction using a collection of 22 clinical isolates from adult and pediatric cystic fibrosis (CF) patients, which included both S. aureus (CF-SA) and P. aeruginosa (CF-PA). We found that when isolated alone, CF-PA and CF-SA expressed varying levels of PYO and norA transcripts, but all four CF-PA/CF-SA pairs isolated concurrently from CF patients produced a low level of PYO and low norA transcript levels, respectively, suggesting a partial adaptation of the two bacteria in circumstances of persistent co-colonization.

Safety of Non-Operating Room Anesthesia With Propofol Sedation in Three Pediatric Patients With Central Sleep Apnea.

Children with central sleep apnea may require sedation for procedures, including brain imaging as part of the evaluation of apnea. However, the safety of deep sedation without a protected airway is not known in this patient population. In this case series, we present 3 children with central sleep apnea who were sedated with propofol for brain imaging in a non-operating room setting. All 3 did well with no complications; those with a home oxygen requirement were on oxygen during the procedure but none experienced apnea, desaturation, or respiratory distress. While obstructive sleep apnea is a known contraindication to deep sedation with propofol, it may be safe in pediatric patients with central sleep apnea. Deep sedation may be a good option for these patients, thereby avoiding the need for general anesthesia and placement of an advanced airway.

Intranasal Dexmedetomidine With Intravenous Midazolam: A Safe and Effective Alternative in the Paediatric MRI Sedation.

Background and aims MRI sedation in paediatrics includes challenges like respiratory depression, maintaining haemodynamic stability and use of neuroprotective drugs, since MRI is performed in remote places outside the operating room with a lack of support staff and nonavailability of choice of medications and equipments. The primary aim was to use a combination of the drugs to encounter the above challenges and look for its efficacy. The secondary aim of the study was to determine the rate of successful completion of MRI in children using a combination of intranasal dexmedetomidine and intravenous midazolam - without the need for rescue sedatives. Methods This is an observational study involving 60 children in the age group between two months and six years undergoing an MRI. Children belonging to the American Society of Anesthesiology (ASA) 1 and 2 were given intranasal dexmedetomidine 3µg/kg, time to onset of sedation was noted and injection of midazolam 0.1 mg/kg was given intravenously. MRI was started once the child was asleep. Children who woke up during the MRI were supplemented with inj. propofol 0.5-1mg/kg and were documented. Results The median time duration for MRI was 38.7 min and the onset of sedation after intranasal dexmedetomidine was 18.7 min. The scan was successfully completed with a combination of intranasal dexmedetomidine and intravenous midazolam in 86.7% and only 13.3% of the children woke up either at the start or in between the scan and required the addition of propofol. Conclusion Drugs used for sedation during MRI should not cause respiratory depression and be safe for the developing brain. The above study has shown that a combination of intranasal dexmedetomidine and intravenous midazolam is effective and safe in performing MRIs in paediatrics.

Impact of clonal lineages on susceptibility of Staphylococcus lugdunensis to chlorhexidine digluconate and chloride benzalkonium.

BACKGROUND: Little is known about susceptibility of Staphylococcus lugdunensis to antiseptics. The objective of this study was to evaluate, at the molecular and phenotypic level, the susceptibility of 49 clinical S. lugdunensis strains (belonging to the seven clonal complexes [CCs] defined by multilocus sequence typing) to two antiseptics frequently used in healthcare settings (chlorhexidine digluconate [CHX] and chloride benzalkonium [BAC]). RESULTS: The minimum inhibitory concentrations (MICs), by broth microdilution method, varied for BAC from 0.25 mg/L to 8 mg/L (MIC50 = 1 mg/L, MIC90 = 2 mg/L) and for CHX from 0.5 mg/L to 2 mg/L (MIC50 = 1 mg/L, MIC90 = 2 mg/L). The BAC and CHX minimum bactericidal concentrations (MBCs) varied from 2 mg/L to 8 mg/L (MBC50 = 4 mg/L, MBC90 = 8 mg/L) and from 2 mg/L to 4 mg/L (MBC50 and MBC90 = 4 mg/L), respectively. A reduced susceptibility to CHX (MIC = 2 mg/L) was observed for 12.2% of the strains and that to BAC (MIC ≥ 4 mg/L) for 4.1%. The norA resistance gene was detected in all the 49 isolates, whereas the qacA gene was rarely encountered (two strains; 4.1%). The qacC, qacG, qacH, and qacJ genes were not detected. The two strains harboring the qacA gene had reduced susceptibility to both antiseptics and belonged to CC3. CONCLUSION: The norA gene was detected in all the strains, suggesting that it could belong to the core genome of S. lugdunensis. S. lugdunensis is highly susceptible to both antiseptics tested. Reduced susceptibility to BAC and CHX was a rare phenomenon. Of note, a tendency to higher MICs of BAC was detected for CC3 isolates. These results should be confirmed on a larger collection of strains.

Viruses in Laboratory Drosophila and Their Impact on Host Gene Expression.

Drosophila melanogaster has one of the best characterized antiviral immune responses among invertebrates. However, relatively few easily transmitted natural virus isolates are available, and so many Drosophila experiments have been performed using artificial infection routes and artificial host-virus combinations. These may not reflect natural infections, especially for subtle phenotypes such as gene expression. Here, to explore the laboratory virus community and to better understand how natural virus infections induce changes in gene expression, we have analysed seven publicly available D. melanogaster transcriptomic sequencing datasets that were originally sequenced for projects unrelated to virus infection. We have found ten known viruses-including five that have not been experimentally isolated-but no previously unknown viruses. Our analysis of host gene expression revealed that numerous genes were differentially expressed in flies that were naturally infected with a virus. For example, flies infected with nora virus showed patterns of gene expression consistent with intestinal vacuolization and possible host repair via the upd3 JAK/STAT pathway. We also found marked sex differences in virus-induced differential gene expression. Our results show that natural virus infection in laboratory Drosophila does indeed induce detectable changes in gene expression, suggesting that this may form an important background condition for experimental studies in the laboratory.

Efflux pump inhibitory potential of indole derivatives as an arsenal against norA over-expressing Staphylococcus aureus.

NorA, an extensively studied efflux pump in Staphylococcus aureus, has been connected to fluoroquinolone, antiseptic, and disinfection resistance. Several studies have also emphasized how efflux pumps, including NorA, function as the first line of defense of S. aureus against antibiotics. In this study, we have screened some chemically synthesized indole derivatives for their activity as efflux pump inhibitors (EPIs). The derivative SMJ-5 was found to be a potent NorA efflux pump inhibitor among the screened indole derivatives, owing to increased ethidium bromide and norfloxacin accumulation in norA over-expressing S. aureus. The combination of SMJ-5 and ciprofloxacin demonstrated the eradication of S. aureus biofilm and prolonged the post-antibiotic effect more than ciprofloxacin alone. SMJ-5 was able to inhibit staphyloxanthin virulence. In in vitro time-kill trials and in vivo efficacy investigations, the combination enhanced the bactericidal activity of ciprofloxacin against S. aureus. Additionally, reverse transcription PCR results revealed that SMJ-5 also inhibits the NorA efflux pump indirectly at the transcriptional level. IMPORTANCE The NorA efflux pump is the most effective resistance mechanism in S. aureus. The clinical importance of NorA efflux pumps is demonstrated by the expression of pump genes in S. aureus strains in response to fluoroquinolones and biocides. Along with the repercussions of decreased fluoroquinolone sensitivity, increasing expression of efflux pump genes by their substrate necessitates the importance of efflux pump inhibitors. Reserpine and verapamil are clinically used to treat ailments and have proven NorA inhibitors, but, unfortunately, the concentration needed for these drugs to inhibit the pump is not safe in clinical settings. In the current study, we have screened some indole derivatives, and among them, SMJ-5 was reported to potentiate norfloxacin and ciprofloxacin at their sub-inhibitory concentration by inhibiting the norA gene transcriptionally. Here we highlight the promising points of this study, which could serve as a model to design a therapeutic EPI candidate against norA over-expressing S. aureus.

Systems, safety, and anaesthesia outside the operating room.

An increasing number of patients are receiving sedation or anaesthesia in locations outside of the operating room. Compared with the operating room, anaesthesia providers working in a non-operating room anaesthesia (NORA) location report significantly lower perceived levels of safety, and higher levels of anxiety, stress, and workload. These results are likely to affect the well-being of staff in NORA locations and are clinically relevant in terms of patient safety.

Resveratrol as an Inhibitor of the NorA Efflux Pump and Resistance Modulator in Staphylococcus aureus.

Staphylococcus aureus can exhibit resistance to various antibiotics. Among its resistance mechanisms, the active efflux of antibiotics can be seen as relevant. This study aimed to evaluate the ability of resveratrol to modulate norfloxacin resistance in S. aureus. The antimicrobial activity of resveratrol was assessed using the broth microdilution method to determine the minimum inhibitory concentration (MIC). Then, the modulatory effect of resveratrol was evaluated using the MIC determination for the antibiotic or ethidium bromide in the presence and absence of resveratrol at a sub-MIC level. The MIC of norfloxacin against S. aureus SA1199B (NorA-overexpressing strain) decreased 16-fold when in the presence of resveratrol, with a similar behavior being observed for ethidium bromide. An evaluation of the ethidium bromide accumulation was also performed, showing that in the presence of resveratrol, the SA1199B strain had augmented fluorescence due to the accumulation of ethidium bromide. Altogether, the results suggested that resveratrol may act by inhibiting NorA. These in vitro data were supported by docking results, with interactions between resveratrol and the NorA efflux pump predicted to be favorable. Our findings demonstrated that resveratrol may modulate norfloxacin resistance through the inhibition of NorA, increasing the effectiveness of this antibiotic against S. aureus.

Bizarre parosteal osteochondromatous proliferation: an educational review.

Bizarre parosteal osteochondromatous proliferation (BPOP) is a surface-based bone lesion belonging to the group of benign chondrogenic tumors. The aim of this review is to familiarize the readers with imaging features and differential diagnosis of BPOP, also addressing pathological presentation and treatment options. The peak of incidence of BPOP is in the third and fourth decades of life, although it can occur at any age. Hands are the most common location of BPOP (55%), followed by feet (15%) and long bones (25%). On imaging, BPOP appears as a well-marginated mass of heterotopic mineralization arising from the periosteal aspect of the bone. Typical features of BPOP are contiguity with the underlying bone and lack of cortico-medullary continuity, although cortical interruption and medullary involvement have been rarely reported. Histologically, BPOP is a benign bone surface lesion characterized by osteocartilaginous proliferation with disorganized admixture of cartilage with bizarre features, bone and spindle cells. Differential diagnosis includes both benign-such as florid reactive periostitis, osteochondroma, subungual exostosis, periosteal chondroma and myositis ossificans-and malignant lesions-such as periosteal chondrosarcoma and surface-based osteosarcoma. Treatment consists of surgical resection. Local recurrences are common and treated with re-excision.Critical relevance statement Bizarre parosteal osteochondromatous proliferation is a benign mineralized mass arising from the periosteal aspect of bone cortex. Multi-modality imaging characteristics, pathology features and differential diagnosis are here highlighted to familiarize the readers with this entity and offer optimal patient care.

Inhibition of Staphylococcus pseudintermedius Efflux Pumps by Using Staphylococcus aureus NorA Efflux Pump Inhibitors.

One promising approach in treating antibiotic-resistant bacteria is to "break" resistances connected with antibacterial efflux by co-administering efflux pump inhibitors (EPIs) with antibiotics. Here, ten compounds, previously optimized to restore the susceptibility to ciprofloxacin (CIP) of norA-overexpressing Staphylococcus aureus, were evaluated for their ability to inhibit norA-mediated efflux in Staphylococcus pseudintermedius and synergize with CIP, ethidium bromide (EtBr), gentamycin (GEN), and chlorhexidine digluconate (CHX). We focused efforts on S. pseudintermedius as a pathogenic bacterium of concern within veterinary and human medicine. By combining data from checkerboard assays and EtBr efflux inhibition experiments, the hits 2-arylquinoline 1, dihydropyridine 6, and 2-phenyl-4-carboxy-quinoline 8 were considered the best EPIs for S. pseudintermedius. Overall, most of the compounds, except for 2-arylquinoline compound 2, were able to fully restore the susceptibility of S. pseudintermedius to CIP and synergize with GEN as well, while the synergistic effect with CHX was less significant and often did not show a dose-dependent effect. These are valuable data for medicinal chemistry optimization of EPIs for S. pseudintermedius and lay the foundation for further studies on successful EPIs to treat staphylococcal infections.