GTExome: Modeling commonly expressed missense mutations in the human genome.

A web application, GTExome, is described that quickly identifies, classifies, and models missense mutations in commonly expressed human proteins. GTExome can be used to categorize genomic mutation data with tissue specific expression data from the Genotype-Tissue Expression (GTEx) project. Commonly expressed missense mutations in proteins from a wide range of tissue types can be selected and assessed for modeling suitability. Information about the consequences of each mutation is provided to the user including if disulfide bonds, hydrogen bonds, or salt bridges are broken, buried prolines introduced, buried charges are created or lost, charge is swapped, a buried glycine is replaced, or if the residue that would be removed is a proline in the cis configuration. Also, if the mutation site is in a binding pocket the number of pockets and their volumes are reported. The user can assess this information and then select from available experimental or computationally predicted structures of native proteins to create, visualize, and download a model of the mutated protein using Fast and Accurate Side-chain Protein Repacking (FASPR). For AlphaFold modeled proteins, confidence scores for native proteins are provided. Using this tool, we explored a set of 9,666 common missense mutations from a variety of tissues from GTEx and show that most mutations can be modeled using this tool to facilitate studies of protein-protein and protein-drug interactions. The open-source tool is freely available at https://pharmacogenomics.clas.ucdenver.edu/gtexome/.

A comparative analysis of Charlson's weighted index of comorbidity and perforated peptic ulcer scores in predicting postoperative mortality and high comprehensive complication index.

BACKGROUND: Limited data exists on Charlson's weighted index of comorbidity (WIC) predictability for postoperative outcomes following perforated peptic ulcer (PPU) surgery. This study assesses the utility of WIC and other predictive scores in forecasting both postoperative mortality and morbidity in PPU. MATERIALS & METHODS: Patients with PPUs operated between 2018 and 2021 in a Malaysian tertiary referral center were included. Clinical data were retrospectively analyzed for association with mortality and morbidity measured with the Comprehensive Complication Index (CCI). Predictability of WIC and other predictors were examined using area under receiver-operator characteristic (ROC) curve (AUC). RESULTS: Among 110 patients included, 18 died (16.4%) and 36 (32.7%) had significant morbidity postoperatively (High CCI, ≥26.2). Both mortality and high CCI were associated with age >65 years, female sex, comorbidities (diabetes mellitus, hypertension, and renal disease), and American Society of Anesthesiologist score >2. Most patients who died had renal dysfunction, metabolic acidosis, lactate >2 mmol/L upon presentation preoperatively. While surgery >24 h after presentation correlated with mortality and high CCI, the benefit of earlier surgery <6 h or <12 h was not demonstrated. WIC (AUC, 0.89; 95% CI, 0.81-0.99) showed similar predictability to Peptic Ulcer Perforation (PULP) (AUC, 0.97; 95% CI, 0.93-1.00) for mortality. PULP effectively predicted high CCI (AUC, 0.83; 95% CI, 0.73-0.93; p < 0.001). CONCLUSION: WIC is valuable in predicting mortality, highlighting the importance of comorbidity in risk assessment. PULP score was effective in predicting both mortality and high CCI. Early identification of patients with high perioperative risk will facilitate patients' triage for escalated care, leading to a better outcome.

A comparative study of anxiety and depression among healthcare workers and non-healthcare workers in Johor, Malaysia during the Covid-19 era.

The outbreak of Coronavirus disease 2019 (Covid-19) has a significant impact on the mental health of the global population. Updates are needed regarding the mental health status among the local population since limited studies were done so far. This research compared the prevalence of anxiety and depression symptoms among HCWs and non-HCWs. We also evaluated the factors associated with anxiety and depression symptoms among these 2 groups. This was a cross-sectional study conducted between September to December 2022. Online questionnaire was distributed to HCWs from 2 tertiary government hospitals. Non-HCWs from various occupational fields were recruited randomly. Generalised Anxiety Disorder 7 (GAD-7) and Patient Health Questionnaire 9 (PHQ-9) were used to screen for anxiety and depression symptoms respectively. Data were analyzed using IBM SPSS version 28.0. 200 questionnaires were distributed to HCWs and non-HCWs respectively. The response rate was 74.5% from HCWs and 82.5% from non-HCWs (P = .07). A total of 236 individuals (105 HCWs and 131 non-HCWs) were included in the study. Majority were female, married, highly educated and worked more than 8 hours per day. There was no significant difference for the prevalence of anxiety (37.2% vs 44.3%, P = .34) and depression symptoms (37.3% vs 35.1%, P = .75) between HCWs and non-HCWs. Among HCWs, poor workplace support (P = .009) and low income (P = .04) were associated with anxiety symptoms. Younger age (P = .02), single status (P = .01) and poor workplace support (P = .006) were associated with depression symptoms. More non-HCWs with a higher educational level were having anxiety and depression symptoms. Single status (P = .03), working away from home (P = .02), poor family support (P = .03) and quarantine as Covid-19 close contact (P = .04) were also associated with depression symptoms among non-HCWs. There is no significant difference between HCWs and non-HCWs experiencing possible anxiety or depressive symptoms in this study. However, attention should be paid to address associated factors identified among each group to promote good mental health.

Expanding the Spectrum of EWSR1::CREM Fusion Tumors: An Unusual Pediatric Intranasal Myxoid Tumor.

EWSR1::CREM gene fusions are increasingly being recognized in a diverse number of soft tissue tumors, including well-defined entities such as angiomatoid fibrous histiocytoma or clear cell sarcoma, and other unclassifiable tumors. As a group, EWSR1::CREM fused tumors often demonstrate primitive spindle or epithelioid cells, myxoid stroma, and a broad immunophenotype. Herein we present an unusual case of a child diagnosed with an intranasal malignant myxoid tumor harboring an EWSR1::CREM gene fusion. To the best of our knowledge, this is the first case of intranasal myxoid tumor with this particular fusion. Diagnosis and management of the case is discussed.

GTExome: Modeling commonly expressed missense mutations in the human genome.

A web application, GTExome, is described that quickly identifies, classifies, and models missense mutations in commonly expressed human proteins. GTExome can be used to categorize genomic mutation data with tissue specific expression data from the Genotype-Tissue Expression (GTEx) project. Commonly expressed missense mutations in proteins from a wide range of tissue types can be selected and assessed for modeling suitability. Information about the consequences of each mutation is provided to the user including if disulfide bonds, hydrogen bonds, or salt bridges are broken, buried prolines introduced, buried charges are created or lost, charge is swapped, a buried glycine is replaced, or if the residue that would be removed is a proline in the cis configuration. Also, if the mutation site is in a binding pocket the number of pockets and their volumes are reported. The user can assess this information and then select from available experimental or computationally predicted structures of native proteins to create, visualize, and download a model of the mutated protein using Fast and Accurate Side-chain Protein Repacking (FASPR). For AlphaFold modeled proteins, confidence scores for native proteins are provided. Using this tool, we explored a set of 9,666 common missense mutations from a variety of tissues from GTEx and show that most mutations can be modeled using this tool to facilitate studies of protein-protein and protein-drug interactions. The open-source tool is freely available at https://pharmacogenomics.clas.ucdenver.edu/gtexome/.

Optical fiber speckle spectrometer based on reversed-lens smartphone microscope.

Smartphones are a potentially powerful platform for scientific instruments. Here, we demonstrate speckle spectroscopy with smartphone-level hardware. This technique promises greater performance thresholds than traditional diffraction gratings. Light is injected into an optical fiber and the emergent speckle patterns are imaged by a reversed-lens smartphone camera. The smartphone then uses an algorithm, running on a mobile computing app, to determine, in less than one second, the (hitherto unknown) input spectrum. We reconstruct a variety of visible-wavelength (470-670 nm) single and multi-peaked spectra using a tunable source. The latter also include a metameric pair, i.e., two spectra that are different, yet represent colors that are indistinguishable to the human eye.

COVID-19 related acute limb ischaemia: A case series.

COVID-19 infection or vaccination is rarely associated with arterial occlusive disease of the extremities. The surgical department of a hospital in Johor, Malaysia, recorded a significant increase in the number of COVID-19-related acute limb ischaemia when the rates of COVID-19 were high both locally and internationally. The clinical presentation and management of acute limb ischaemia associated with COVID-19 infection or vaccination are largely underreported in Johor. Herein, we report a case series of 12 patients managed with strategies ranging from purely anticoagulation to catheter-directed thrombolysis and surgical embolectomy. This case series describes the clinical presentation, risk profiles, treatment approaches and limb outcomes of the patients. The amputation rate was high in view of unfavourable factors, including delayed presentation, high-risk factors and severe COVID-19. Three cases of potential COVID-19 vaccine-related acute limb ischaemia were included. COVID-19-related acute limb ischaemia can be minimised with heightened alert, preemptive optimisation with proper hydration and consideration for early prophylactic anticoagulation in high-risk cases.

Paediatric actinomycosis: A 16-year, single-institution retrospective review of cases.

AIM: Actinomycosis is a rare subacute to chronic granulomatous infection which can mimic other infectious or malignant diseases. This study examined the epidemiology and treatment outcome of actinomycosis in children. METHODS: A retrospective study on children admitted for actinomycosis in a tertiary paediatric hospital in Singapore, from January 2004 to December 2020. Clinical profile, therapeutic interventions and outcomes were examined. RESULTS: A total of 10 patients were identified; 7 were female. The median age at first presentation was 9.8 years (range 4.7-15.7). The most common presenting symptom was fever (n = 6, 60%), followed by facial or neck swelling (n = 3, 30%) and ear pain (n = 3, 30%). Actinomycosis occurred predominantly in the orocervicofacial region (n = 6, 60%). Four patients (40%) had preceding dental infections in the form of dental caries or gingivitis. One patient had poorly controlled insulin-dependent diabetes mellitus. Actinomycosis was confirmed via culture in four patients, histopathology in four patients and both methods in two patients. All except one patient (n = 9, 90%) underwent surgical procedures. All patients received ampicillin or amoxicillin/clavulanate or other beta-lactams, for a median duration of 6.5 months (range 1.5-14). Complications included osteomyelitis (n = 4, 40%), mastoiditis (n = 2, 20%), brain abscess (n = 1, 10%) and recurrent neck abscess (n = 1, 10%). There was no mortality and all patients achieved complete resolution. CONCLUSIONS: Paediatric actinomycosis was rare in our 16-year review, but had a high complication rate. It can occur in immunocompetent patients, and dental infection was the predominant risk factor identified. Prognosis was excellent after surgical intervention and appropriate antimicrobial therapy.

Outcome of childhood epistaxis with treatment of allergic rhinitis: a randomized controlled study.

The purpose of this study is to (1) to determine if treatment of underlying allergic rhinitis (AR) in children will affect epistaxis outcome, (2) to compare efficacy of three outpatient AR treatment regimens in epistaxis outcomes, and (3) to investigate potential factors in the pathogenesis of epistaxis with underlying AR. A single-blind randomized-controlled study was conducted in the Otolaryngology clinic in KK Women's and Children's Hospital. Sixty children aged below 18 years with underlying untreated AR, with first presentation of epistaxis, were randomized to three different AR treatments: treatment 1, antihistamine (20 patients); treatment 2, nasal steroid spray (20 patients); and treatment 3, both antihistamine and nasal steroid spray (20 patients). Epistaxis severity and frequency were assessed. Pre-treatment, 95% of patients within each of the three treatment groups described epistaxis symptoms. Post-treatment, there was improvement in epistaxis outcome (resolution of epistaxis) with 20% (4/20), 40% (8/20), and 60% (12/20) of patients in treatment groups 1 (antihistamine), 2 (nasal steroid spray), and 3 (combined therapy) respectively, who reported resolution of epistaxis. Treatment regimens containing nasal steroid spray resulted in greater improvement of epistaxis severity and frequency. Combined therapy (treatment 3) resulted in the best epistaxis outcome at 1-month follow-up. Majority (90%) reported nose-picking/rubbing behavior. CONCLUSIONS: Intranasal corticosteroids are superior to oral antihistamines in relieving itch or rhinorrhea in AR. Intranasal corticosteroids may be important in treating epistaxis with underlying AR, because digital trauma from itch/rhinorrhea-related nose-picking/rubbing frequently leads to epistaxis. Results from this study will be important to primary and emergency physicians, community pediatricians, and pediatric allergists and otolaryngologists. WHAT IS KNOWN: • Childhood epistaxis commonly co-exists with allergic rhinitis (AR), causing significant symptoms and distress to patients. • There are currently no studies reporti ng on epistaxis outcome aft er treatment of underlying AR. WHAT IS NEW: • This is a single-blind randomized-controlled study of 60 children aged below 18 years with underlying untreated AR, with first presentation of epistaxis to a children's hospital in Singapore Patients were randomized to three different regimens to treat AR: treatment 1, antihistamine; treatment 2, nasal steroid spray; and treatment 3, both antihistamine and nasal steroid spray. • Treatment regimens containing nasal steroid spray improved epistaxis outcomes, with combined therapy of antihistamine and nasal steroid spray resulting in the best outcome for resolution of epistaxis among the three treatment regimens.

Genetic optimization of mid-infrared filters for a machine learning chemical classifier.

Miniaturized mid-infrared spectrometers present opportunities for applications that range from health monitoring to agriculture. One approach combines arrays of spectral filters with infrared photodetectors, called filter-array detector-array (FADA) microspectrometers. A paper recently reported a FADA microspectrometer in tandem with machine learning for chemical identification. In that work, a FADA microspectrometer with 20 filters was assembled and tested. The filters were band-pass, or band-stop designs that evenly spanned the microspectrometer's operating wavelength range. However, given that a machine learning classifier can be trained on an arbitrary filter basis, it is not apparent that evenly spaced filters are optimal. Here, through simulations with noise, we use a genetic algorithm to optimize six bandpass filters to best identify liquid and gaseous chemicals. We report that the classifiers trained with the optimized filter sets outperform those trained with evenly spaced filter sets and those handpicked to target the absorption bands of the chemicals investigated.

Metabolovigilance: Associating Drug Metabolites with Adverse Drug Reactions.

The Metabolovigilance database (https://pharmacogenomics.clas.ucdenver.edu/pharmacogenomics/side-effect/) is a single repository of information on over 15,920 pharmaceuticals and the compounds expected to result from metabolism of these drugs. Metabolovigilance functions as both a web server, providing data directly to users and as a web application, applying user inputs to create logic statements that curate the data presented or downloaded. Using this tool, it is easy to collect information on drugs, their side effects, and the metabolites associated with specific side effects. Information on these compounds can be sorted based on physical properties of the drugs and their metabolites. All of this information can be viewed, sorted, and downloaded for use in other applications. This open-access tool will facilitate molecular studies on the causes of adverse drug reactions and is well suited to integrate with genomic data furthering the goals of personalized medicine.

Knowledge, Attitude and Practices Towards Cryptosporidium Among Public Swimming Pool Patrons and Staff in Western Australia.

PURPOSE: There is a dearth of research conducted on the Knowledge, Attitude and Practices (KAP) of swimming pool patrons and staff to determine their understanding of the importance of Cryptosporidium and its transmission in swimming pools. METHODS: We conducted a KAP survey of public swimming pool patrons (n = 380) and staff (n = 40) attending five public swimming pools in Western Australia (WA). RESULTS: Knowledge, attitudes and practices (KAP) of Cryptosporidium varied between patrons and staff but were generally limited. Only 26.1% and 25.0% of patrons and staff had heard of Cryptosporidium, while 17.4% and 10.0% knew that it causes diarrhoea, respectively. Thirty-one percent of patrons were aware of their pool policy concerning gastroenteritis and Cryptosporidium, compared to 62.5% of staff. Less than 50% of patrons demonstrated awareness of how features within the pool environment were relevant to the control of Cryptosporidium. Only about a third of patrons (35%) and staff (37.5%) were aware that showering before swimming reduced the risk of gastroenteritis. CONCLUSION: Raising awareness about hygiene-related practices through the delivery of targeted health education messages to the general public is essential to reduce the burden of Cryptosporidium infections in aquatic environments.

Traumatic Cochlear Implant Electrode Extrusion: Considerations, Management, and Outcome.

Cochlear implantation is the mainstay for patients with severe to profound hearing loss that do not benefit from hearing aids. Falls and head trauma can cause direct damage to the implant, of which hard failure is the most common complication. Traumatic electrode migration is an uncommon occurrence. Our patient underwent successful electrode advancement of a partially migrated, normal functioning electrode two months after head injury. We discuss the factors influencing the decision-making process, progress, and outcomes.

Case series of retained rectal foreign body. A Malaysian experience.

Retained rectal foreign body, with its associated social stigma, is a medical condition that is infrequently reported in Malaysia. We report the surgical management of five cases of retained foreign objects in the rectum seen over a one-year period. There were three young and two elderly male patients. One of the elderly patients presented with altered bowel habits and an abdominal mass that mimicked a symptomatic colonic tumor. All patients had an abdominal radiograph which clinched the diagnosis of a retained foreign rectal body. Successfully retrieved objects included two bottles, one bidet device, and two sex toys. Open surgery for retrieval of the impacted rectal foreign body was required in one patient. All underwent successful retrievals without any adverse postoperative complications. In our case series, retained rectal foreign bodies were observed only in the male gender. The age presentation was bimodal, with age groups in the twenties and sixties. The treatment options used for the retrieval of these impacted foreign bodies included transanal extraction or explorative laparotomy. Proximal migration and delayed presentation are possible indications for the latter approach.

Good hearing outcome in children recovering from non-polio enteroviral meningitis.

AIM: Evaluation of hearing outcome in children following non-polio enteroviral meningitis (EVM). METHODS: We reviewed hearing outcome of children, aged ≤15 years, with EVM managed at our institution over a 4-year period from July 2008 to July 2011 and January-December 2015. Children with concomitant bacterial infections, and those who required intensive care, or with a prior history of hearing impairment or immunodeficiency were excluded. Data on demographics, medical history, presentation and outcome of hearing screen were collected. The children attended post-meningitis review and hearing screen utilising transient-evoked otoacoustic emission testing at 8-10 weeks. Children who failed the transient-evoked otoacoustic emission testing and those with caregiver concerns were referred to otolaryngology for comprehensive audiologic evaluation. RESULTS: The study cohort consisted of 179 children, aged from 3 days to 15 years, of whom 158 (89%) were younger than 90 days of age. Eleven were preterm infants. A total of 158 children had received intravenous gentamicin at 5-7.5 mg/kg/day for a median duration of 2 days. All 179 study participants were found to have good hearing post EVM. CONCLUSION: Hearing outcome in children recovering from EVM is good.

Post-colonoscopy diverticulitis: A systematic review.

BACKGROUND: Post-colonoscopy diverticulitis is increasingly recognized as a potential complication. However, the evidence is sparse in the literature. AIM: To systematically review all available evidence to describe the incidence, clinical course with management and propose a definition. METHODS: The databases PubMed, EMBASE and Cochrane databases were searched using with the keywords up to June 2020. Additional manual search was performed and cross-checked for additional references. Data collected included demographics, reason for colonoscopy, time to diagnosis, method of diagnosis (clinical vs imaging) and management outcomes. RESULTS: A total of nine studies were included in the final systematic review with a total of 339 cases. The time to diagnosis post-colonoscopy ranged from 2 h to 30 d. Clinical presentation for these patients were non-specific including abdominal pain, nausea/vomiting, per rectal bleeding and chills/fever. Majority of the cases were diagnosed based on computed tomography scan. The management for these patients were similar to the usual patients presenting with diverticulitis where most resolve with non-operative intervention (i.e., antibiotics and bowel rest). CONCLUSION: The entity of post-colonoscopy diverticulitis remains contentious where there is a wide duration post-procedure included. Regardless of whether this is a true complication post-colonoscopy or a de novo event, early diagnosis is vital to guide appropriate treatment. Further prospective studies especially registries should include this as a complication to try to capture the true incidence.