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Intraductal papilloma of the breast is a rare benign tumour. The polypoid lesions arising from the nipple surface include papillomas and fibroepithelial stromal polyps. These lesions must be distinguished from malignant nipple lesions, such as Paget’s disease of the nipple or malignant breast conditions involving the nipple. Solitary papillomas (solitary intraductal papillomas) are single tumours that often grow in the large milk ducts near the nipple. They are a common cause of clear or bloody nipple discharge, especially when it comes from only one breast, and can be felt as a small lump behind or next to the nipple. Papillomas may also be found in small ducts in areas of the breast farther from the nipple. Multiple papillomas, which are growths that are less prone to generate nipple discharge, were present in this case. In papillomatosis, there are very small areas of cell growth within the ducts, but they aren’t as distinct as papillomas are. In order to distinguish between these disorders, a thorough clinical examination and imaging are essential. This case report describes a 36-year-old female who presented with swelling from the left nipple. Sonography of the left breast revealed a dilated duct in the left retro-areolar region with a focal isoechoic component within the duct {American College of Radiology Breast Imaging Reporting and Data System (ACR BI-RADS 4B)}. The patient underwent core excision of the duct, and histopathological analysis confirmed the diagnosis of papilloma with changes of adenosis without atypia.

Pustular psoriasis is a specialized variant of psoriasis which can be life threatening if not treated at the earliest. The pathogenesis has been recently linked to the role of interleukin 36. Apart from the corticosteroids, systemic antipsoriatics like acitretin, cyclosporine and methotrexate have been used with some success though unpredictable. With recent identification of role of IL-36 in the pathogenesis of pustular psoriasis, biologics targeting the IL-36 receptors have been used to manage the situation with high degree of success. This narrative review deals with the recent concepts of pathogenesis of pustular psoriasis as well as the current management scenario.

Psoriasis is a common chronic, immune-mediated inflammatory skin disease associated with various comorbidities. Managing psoriasis is often challenging as the therapy is decided based on the area of the disease, associated comorbidities and impairment in quality of life, besides the patient’s preference. Making progress in the development of new molecules that can be used topically or orally, effectively controlling the disease with minimal side effects and providing long-lasting remissions are the needs of the hour. Recent developments in understanding the complexities of the pathogenesis of psoriasis have resulted in the reinforcement of treatment modalities, leading to the evolution of various biologics and small-molecule inhibitors. In comparison with biologics, both patients and treating physicians prefer small molecules for various reasons such as avoiding injections and side effects that are associated with biologics biologics. Moreover small molecules are economical than biologics. Newer small molecules, both topical and oral, are promising additions to the therapeutic arsenal in the management of psoriasis in the future.

The coronavirus SARS-CoV-2 causes the severe disease COVID-19. SARS-CoV-2 infection is initiated by interaction of the viral spike protein and host receptor angiotensin-converting enzyme 2 (ACE2). We report an improved bright and reversible fluorogenic reporter, named SURF (split UnaG-based reversible and fluorogenic protein-protein interaction reporter), that we apply to monitor real-time interactions between spike and ACE2 in living cells. SURF has a large dynamic range with a dark-to-bright fluorescence signal that requires no exogenous cofactors. Utilizing this reporter, we carried out a high-throughput screening of small-molecule libraries. We identified three natural compounds that block replication of SARS-CoV-2 in both Vero cells and human primary nasal and bronchial epithelial cells. Cell biological and biochemical experiments validated all three compounds and showed that they block the early stages of viral infection. Two of the inhibitors, bruceine A and gamabufotalin, were also found to block replication of the Delta and Omicron variants of SARS-CoV-2. Both bruceine A and gamabufotalin exhibited potent antiviral activity in K18-hACE2 and wild-type C57BL6/J mice, as evidenced by reduced viral titres in the lung and brain, and protection from alveolar and peribronchial inflammation in the lung, thereby limiting disease progression. We propose that our fluorescent assay can be applied to identify antiviral compounds with potential as therapeutic treatment for COVID-19 and other respiratory diseases.

**Introduction**: The New Zealand Accidents Compensation Corporation received 28,901 new claims for maxillofacial fractures between January 2018 and December 2021, at an annual cost of NZ$70–80 million. We have previously reported interpersonal violence as the most common cause of maxillofacial fractures disproportionately affecting young Māori males. This study provides an update on the incidence and cause of maxillofacial fractures with a specific review of the impact of COVID-19 lockdowns. **Methods**: Patients referred to the Wellington Regional Plastic, Maxillofacial and Burns Unit from 1 January 2018 to 31 December 2021 were identified from our maxillofacial fracture database. Age, ethnicity, gender, cause of injury, risk factors, and fracture pattern and management were analysed. **Results**: Out of 1281 patients identified, 75.2 per cent were male, most commonly (38.7%) aged 16–30 years. Interpersonal violence, falls and sports accounted for 37.6 per cent, 24.9 per cent, and 24.0 per cent of all maxillofacial fractures, respectively. Māori (22.0%) and New Zealand Europeans (55.7%) were the two largest groups, most commonly affected by interpersonal violence and falls, respectively. There was a relative increase in referral rates for females and for those older than 60 years (1.78 per 10 person-days versus 0.014 per 10 person-days and 4.2 per 10 person-days versus 1.8 per 10 person-days, respectively) and a decrease in the rates of interpersonal violence and sports related referrals (1.2 per 10 person-days versus 3.4 per 10 person-days and 0.41 per 10 person-days versus 2.19 per 10 person-days, respectively) during COVID-19 lockdowns, compared with outside lockdown. **Conclusions**: Interpersonal violence remains the main cause of maxillofacial fractures. There is a need for a national prevention strategy to reduce this. During COVID-19 lockdowns, there was a relative increase in the referral rates of females aged 60 years and over. Both sports and interpersonal violence showed significantly reduced referral rates during lockdowns, while falls, road traffic accidents and other were referred at a similar rate as out of lockdown.

Myxofibrosarcoma is an aggressively malignant soft-tissue neoplasm of the upper or lower extremities that occurs in adults. At the time of diagnosis, upto 73% of cancer patients complain of varying degrees of pain. The ultimate goal of treatment is pain relief and functional recovery. The authors describe the case of a 59-year-old female patient who presented with complaints of excruciating brachialgia of the right upper limb. She had a pain score of 10 based on the Visual Analogue Scale (VAS 0-10). Her pain was initially managed conservatively with systemic analgesics but it failed to offer adequate relief. Often, there is an inadequate response to conservative treatment. These patients may benefit from various interventional modalities. Hence, epidural neurolysis with phenol was done by slowly injecting 2 mL of 6% aqueous phenol into the epidural space under Computed Tomography (CT) and fluoroscopy guidance. Upon follow-up, the patient’s Visual Analog Scale (VAS) was recorded as one, morphine consumption decreased with eventual discontinuation, and paraesthesia had reduced by 50%. This patient was suffering from chronic pain, which significantly reduced her Quality of Life (QoL). The injection of phenol into the appropriate space resulted in satisfactory sustained analgesia. She did not have any sensory or motor loss. Her pain was adequately controlled by paracetamol 500 mg as needed. The patient remained pain-free for five months after the procedure but eventually succumbed to her illness.

Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) is highly contagious. The use of other barrier techniques, in addition to personal protective equipment (PPE), to limit aerosolization and protect against contamination may also be helpful. Design: This is a prospective, randomized, single-blind, comparative study to compare the efficacy of aerosol box with the Mayo trolley containment setup during intubation. Materials and Methods: The two setups were compared for ease and time taken for intubation, restriction of hand movement, difficulty in accessing equipment, difficulty in railroading of endotracheal tube (ETT) over a bougie, and general satisfaction of operator during intubation using the C-MAC video laryngoscope. The mean time taken for endotracheal intubation (ETI) was compared using the unpaired t-test, and the rest of the categorical variables were presented as proportions and percentages. Results: The mean time taken for ETI using the Mayo trolley was 42.6 seconds as compared to 54.5 seconds with an aerosol box. The operator was more satisfied with the Mayo trolley setup. Conclusion: The Mayo trolley containment setup is an inexpensive and readily available alternative to the aerosol box in any setting, with a lesser time taken to intubation and lesser restriction of hand movement, easy accessibility of equipment, and easy railroading of ETT over a bougie.

Purpose: Foreign body reaction to non-absorbable alloplastic orbital implants utilized for bony reconstruction are infrequently documented in the literature. We present the workup and surgical management of a giant cystic mass encapsulating a patient's alloplastic orbital implant, which was ultimately deemed to be a result of foreign body reaction. Observations: A 41-year-old male patient with distant history of a right orbital floor fracture had undergone repair with the placement of a nylon foil implant. The patient presented twenty years later with progressive ipsilateral globe proptosis and was found to have a giant inferior orbital cyst. Surgical exploration and removal of the implant and capsule were performed. Histopathology confirmed a delayed foreign body reaction around the patient's alloplastic implant. Conclusions: Alloplastic implants may result foreign body reaction and cyst encapsulation as a delayed complication.

Lumbar incisional hernia is an uncommon complication that affects the abdominal wall integrity, accounting for approximately 3.5% of all cases. It typically occurs following open nephrectomy or aortic aneurysm repair surgeries. Although rare, lumbar hernias can lead to discomfort, aesthetic issues, or even intestinal obstruction. In extremely rare cases, lumbar herniation of the liver can occur. Here, the authors present a case of a 60-year-old female patient with liver herniation through a lumbar incisional hernia and a history of pyelolithotomy for renal calculi. The authors performed an open hernia repair with meshplasty. Lumbar incisional hernias are rare and still difficult to manage. Computed tomography is the diagnostic method of choice in the evaluation of the parietal wall defect to choose the appropriate therapeutic management. Surgical management modalities are still poorly codified, with no precise recommendations, and this is probably due to the relative rarity of the cases.

Foreign body retention in the neck may be either traumatic or iatrogenic. Penetrating neck injuries with retained bodies are critical, as the neck serves as a passage for structures essential to life. Therefore, prompt detection and retrieval of the foreign body are paramount in preventing mortality. Here, authors present a case in which a successful surgical retrieval was performed without any postprocedural complications, despite the patient presenting relatively late after the injury. In this case report, a 23-year-old male labourer presented with a right-sided neck swelling two months after a workplace injury involving a shattered metal plate. Imaging confirmed a 15×5 mm hyperdense metallic object penetrating the sternocleidomastoid muscle. Successful open exploration extracted a 1.5 cm metallic shard at the C6 vertebral level, with no major vessel or airway damage. Postoperatively, the patient exhibited no movement restrictions, highlighting the atypical presentation of a retained metallic foreign body and the importance of timely intervention and comprehensive imaging for successful management.

Understanding viral tropism is an essential step toward reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, decreasing mortality from coronavirus disease 2019 (COVID-19) and limiting opportunities for mutant strains to arise. Currently, little is known about the extent to which distinct tissue sites in the human head and neck region and proximal respiratory tract selectively permit SARS-CoV-2 infection and replication. In this translational study, we discover key variabilities in expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential SARS-CoV-2 entry factors, among the mucosal tissues of the human proximal airways. We show that SARS-CoV-2 infection is present in all examined head and neck tissues, with a notable tropism for the nasal cavity and tracheal mucosa. Finally, we uncover an association between smoking and higher SARS-CoV-2 viral infection in the human proximal airway, which may explain the increased susceptibility of smokers to developing severe COVID-19. This is at least partially explained by differences in interferon (IFN)-β1 levels between smokers and non-smokers.

Abstract With concurrent global epidemics of chronic pain and opioid use disorders, there is a critical need to identify, target and manipulate specific cell populations expressing the mu-opioid receptor (MOR). However, available tools and transgenic models for gaining long-term genetic access to MOR+ neural cell types and circuits involved in modulating pain, analgesia and addiction across species are limited. To address this, we developed a catalog of MOR promoter (MORp) based constructs packaged into adeno-associated viral vectors that drive transgene expression in MOR+ cells. MORp constructs designed from promoter regions upstream of the mouse Oprm1 gene (mMORp) were validated for transduction efficiency and selectivity in endogenous MOR+ neurons in the brain, spinal cord, and periphery of mice, with additional studies revealing robust expression in rats, shrews, and human induced pluripotent stem cell (iPSC)-derived nociceptors. The use of mMORp for in vivo fiber photometry, behavioral chemogenetics, and intersectional genetic strategies is also demonstrated. Lastly, a human designed MORp (hMORp) efficiently transduced macaque cortical OPRM1+ cells. Together, our MORp toolkit provides researchers cell type specific genetic access to target and functionally manipulate mu-opioidergic neurons across a range of vertebrate species and translational models for pain, addiction, and neuropsychiatric disorders.

ObjectiveMulti-center implementation of rapid whole genome sequencing with assessment of the clinical utility of rapid whole genome sequencing (rWGS), including positive, negative and uncertain results, in admitted infants with a suspected genetic disease.Study designrWGS tests were ordered at eight hospitals between November 2017 and April 2020. Investigators completed a survey of demographic data, Human Phenotype Ontology (HPO) terms, test results and impacts of results on clinical care.ResultsA total of 188 patients, on general hospital floors and intensive care unit (ICU) settings, underwent rWGS testing. Racial and ethnic characteristics of the tested infants were broadly representative of births in the country at large. 35% of infants received a diagnostic result in a median of 6 days. The most common HPO terms for tested infants indicated an abnormality of the nervous system, followed by the cardiovascular system, the digestive system, the respiratory system and the head and neck. Providers indicated a major change in clinical management because of rWGS for 32% of infants tested overall and 70% of those with a diagnostic result. Also, 7% of infants with a negative rWGS result and 23% with a variant of unknown significance (VUS) had a major change in management due to testing.ConclusionsOur study demonstrates that the implementation of rWGS is feasible across diverse institutions, and provides additional evidence to support the clinical utility of rWGS in a demographically representative sample of admitted infants and includes assessment of the clinical impact of uncertain rWGS results in addition to both positive and negative results.

The respiratory disease COVID-19 is caused by the coronavirus SARS-CoV-2. Here we report the discovery of ethacridine as a potent drug against SARS-CoV-2 (EC50 ~ 0.08 μM). Ethacridine was identified via high-throughput screening of an FDA-approved drug library in living cells using a fluorescence assay. Plaque assays, RT-PCR and immunofluorescence imaging at various stages of viral infection demonstrate that the main mode of action of ethacridine is through inactivation of viral particles, preventing their binding to the host cells. Consistently, ethacridine is effective in various cell types, including primary human nasal epithelial cells that are cultured in an air-liquid interface. Taken together, our work identifies a promising, potent, and new use of the old drug via a distinct mode of action for inhibiting SARS-CoV-2.

Emerging evidence points toward an intricate relationship between the pandemic of coronavirus disease 2019 (COVID-19) and diabetes. While preexisting diabetes is associated with severe COVID-19, it is unclear whether COVID-19 severity is a cause or consequence of diabetes. To mechanistically link COVID-19 to diabetes, we tested whether insulin-producing pancreatic β cells can be infected by SARS-CoV-2 and cause β cell depletion. We found that the SARS-CoV-2 receptor, ACE2, and related entry factors (TMPRSS2, NRP1, and TRFC) are expressed in β cells, with selectively high expression of NRP1. We discovered that SARS-CoV-2 infects human pancreatic β cells in patients who succumbed to COVID-19 and selectively infects human islet β cells in vitro. We demonstrated that SARS-CoV-2 infection attenuates pancreatic insulin levels and secretion and induces β cell apoptosis, each rescued by NRP1 inhibition. Phosphoproteomic pathway analysis of infected islets indicates apoptotic β cell signaling, similar to that observed in type 1 diabetes (T1D). In summary, our study shows SARS-CoV-2 can directly induce β cell killing.

Acne vulgaris is one of the most common disorders of the pilosebaceous unit, affecting around 9.4% of the global population. The principal or preliminary lesions of acne are comedones, which represent the follicular dilation and hypercornification secondary to androgen hypersensitivity. Although the diagnosis of acne is rarely difficult for an experienced dermatologist, we rarely come across various other dermatoses that clinically resemble comedones yet have a different pathophysiology and poorly respond to treatment. Not all disorders that have comedone-like lesions are acne. These disorders should be kept in mind when comedones occur in an unusual site, age, or pattern. This review article mainly focuses and highlights the salient features of multiple non-acne disorders that present with open comedone-like lesions along with an approach to the diagnosis and its management.

The coronavirus SARS-CoV-2 is the causative agent of the ongoing severe acute respiratory disease pandemic COVID-19. Tissue and cellular tropism is one key to understanding the pathogenesis of SARS-CoV-2. We investigate the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of human donors using a diverse panel of banked tissues. Here, we report our discovery that the ACE2 receptor protein robustly localizes within the motile cilia of airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during host respiratory transmission. We further determine whether ciliary ACE2 expression in the upper airway is influenced by patient demographics, clinical characteristics, comorbidities, or medication use, and show the first mechanistic evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) does not increase susceptibility to SARS-CoV-2 infection through enhancing the expression of ciliary ACE2 receptor. These findings are crucial to our understanding of the transmission of SARS-CoV-2 for prevention and control of this virulent pathogen.

BackgroundEndoscopic endonasal approaches pose the potential risk of olfactory loss. Loss of olfaction and potentially taste can be permanent and greatly affect patients' quality of life. Treatments for olfactory loss have had limited success. Omega-3 supplementation may be a therapeutic option with its effect on wound healing and nerve regeneration.ObjectiveTo evaluate the impact on olfaction in patients treated with omega-3 supplementation following endoscopic skull base tumor resection.MethodsIn this multi-institutional, prospective, randomized controlled trial, 110 patients with sellar or parasellar tumors undergoing endoscopic resection were randomized to nasal saline irrigations or nasal saline irrigations plus omega-3 supplementation. The University of Pennsylvania Smell Identification Test (UPSIT) was administered preoperatively and at 6 wk, 3 mo, and 6 mo postoperatively.ResultsEighty-seven patients completed all 6 mo of follow-up (41 control arm, 46 omega-3 arm). At 6 wk postoperatively, 25% of patients in both groups experienced a clinically significant loss in olfaction. At 3 and 6 mo, patients receiving omega-3 demonstrated significantly less persistent olfactory loss compared to patients without supplementation (P = .02 and P = .01, respectively). After controlling for multiple confounding variables, omega-3 supplementation was found to be protective against olfactory loss (odds ratio [OR] 0.05, 95% CI 0.003-0.81, P = .03). Tumor functionality was a significant independent predictor for olfactory loss (OR 32.7, 95% CI 1.15-929.5, P = .04).ConclusionOmega-3 supplementation appears to be protective for the olfactory system during the healing period in patients who undergo endoscopic resection of sellar and parasellar masses.

Choledochal cyst is a congenital disease of the biliary tract with extrahepatic and/or intrahepatic biliary tree dilatation. There is a female majority (4:1). Controlling biliary sepsis and curing pancreatitis are prerequisites of surgery. Here, a 35-year-old female patient, came with complaints of epigastric and right upper abdominal pain for three days. On examination per abdomen was soft, non distended, right hypochondriac tenderness was present, no guarding, bowel sounds were audible. Magnetic Resonance Cholangiopancreatography (MRCP) was done which showed fusiform dilatation of Common Bile Duct (CBD), Common Hepatic Duct (CHD), right and left hepatic duct, along with mild dilatation of central intrahepatic biliary radicals (4.8-5 mm)- suggestive of choledochal cyst type IVA. Hepatico-duodenostomy was done. The entire extrahepatic biliary tree should be removed when the choledochal cyst is diagnosed whether or not symptoms are present. Despite being congenital, the condition is typically discovered in adulthood as well. The treatment of choledochal cysts has evolved. The current standard of care is cyst excision and hepaticojejunostomy.

Key Clinical Message We report two, genotypically identical but phenotypically distinct cases of Schaaf‐Yang syndrome and propose the early use of Genome Sequencing in patients with nonspecific presentations to facilitate the early diagnosis of children with rare genetic diseases and improve overall health care outcomes.

Abstract Recurrence and biochemical remission rates vary widely among different histological subtypes of pituitary adenoma. In this prospective study, we evaluated 107 consecutive primary pituitary adenomas operated on by a single neurosurgeon including 28 corticotroph, 27 gonadotroph, 24 somatotroph, 17 lactotroph, 5 null-cell and 6 plurihormonal. In each case, we performed direct endoscopic intraoperative inspection of the medial wall of the cavernous sinus, which was surgically removed when invasion was visualized. This was performed irrespective of tumor functional status. Medial wall resection was performed in 47% of pituitary adenomas, and 39/50 walls confirmed pathologic evidence of invasion, rendering a positive predictive value of intraoperative evaluation of medial wall invasion of 78%. We show for the first-time dramatic disparities in the frequency of medial wall invasion among pathological subtypes. Somatotroph tumors invaded the medial wall much more often than other adenoma subtypes, 81% intraoperatively and 69% histologically, followed by plurihormonal tumors (40%) and gonadotroph cell tumors (33%), both with intraoperative positive predictive value of 100%. The least likely to invade were corticotroph adenomas, at a rate of 32% intraoperatively and 21% histologically, and null-cell adenomas at 0%. Removal of the cavernous sinus medial wall was not associated with permanent cranial nerve morbidity nor carotid artery injury, although 4 patients (all Knosp 3-4) experienced transient diplopia. Medial wall resection in acromegaly resulted in the highest potential for biochemical remission ever reported, with an average postoperative day 1 GH levels of 0.96 ug/L and surgical remission rates of 92% based on normalization of IGF-1 levels after surgery (mean = 15.56 months; range 3–30 months). Our findings suggest that tumor invasion of the medial wall of the cavernous sinus may explain the relatively low biochemical remission rates currently seen for acromegaly and illustrate the relevance of advanced intradural surgical approaches for successful and durable outcomes in endonasal pituitary surgery for functional adenomas.