Index Case Research Articles

Evaluation of Severe ultrasound and gene diagnosis in cardiac index and shock patient index of shock patients

BACKGROUND: The kidney is the most vulnerable organ in severe patients. In severe cases, the fatality rate of acute kidney damage is as high as 30% ∼ 60%. Severe ultrasound is a non-invasive method to evaluate renal blood flow. It can give a semi-quantitative score of renal blood flow and measure the Resistance Index (RI), which can reflect renal artery blood flow to a certain extent. OBJECTIVE: There is little literature on hemodynamic regulation in septic shock patients, but almost no research report on the relationship between hemodynamics and RI exists. Therefore, this paper proposed the analysis of severe ultrasound and gene diagnosis in cardiac index and peripheral vascular RI of shock patients. METHODS: This paper mainly expounded on detecting renal function parameters and RI in patients with viral shock to understand further the correlation between them and renal flow and RI. RESULTS: It could be seen from the experimental results that the P values before and after resuscitation in the two groups with and without elevated Cardiac Output (CO) were 0.41 and 0.12, respectively, which were more significant than 0.05. CONCLUSION: RI had no apparent relationship with CO, and RI could not be used as an evaluation index for patients with early septic shock.

Simultaneous Detection of Common Founder Mutations Using a Cost-Effective Deep Sequencing Panel.

Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous group of diseases which cause visual loss due to Mendelian mutations in over 250 genes, making genetic diagnosis challenging and time-consuming. Here, we developed a new tool, CDIP (Cost-effective Deep-sequencing IRD Panel) in which a simultaneous sequencing of common mutations is performed. CDIP is based on simultaneous amplification of 47 amplicons harboring common mutations followed by next-generation sequencing (NGS). Following five rounds of calibration of NGS-based steps, CDIP was used in 740 IRD samples. The analysis revealed 151 mutations in 131 index cases. In 54 (7%) of these cases, CDIP identified the genetic cause of disease (the remaining were single-heterozygous recessive mutations). These include a patient that was clinically diagnosed with retinoschisis and found to be homozygous for NR2E3-c.932G>A (p.R311Q), and a patient with RP who is hemizygous for an RPGR variant, c.292C>A (p.H98N), which was not included in the analysis but is located in proximity to one of these mutations. CDIP is a cost-effective deep sequencing panel for simultaneous detection of common founder mutations. This protocol can be implemented for additional populations as well as additional inherited diseases, and mainly in populations with strong founder effects.

AP2A2 mutation and defective endocytosis in a Malian family with hereditary spastic paraplegia

Hereditary spastic paraplegia (HSP) comprises a large group of neurogenetic disorders characterized by progressive lower extremity spasticity. Neurological evaluation and genetic testing were completed in a Malian family with early-onset HSP. Three children with unaffected consanguineous parents presented with symptoms consistent with childhood-onset complicated HSP. Neurological evaluation found lower limb weakness, spasticity, dysarthria, seizures, and intellectual disability. Brain MRI showed corpus callosum thinning with cortical and spinal cord atrophy, and an EEG detected slow background in the index patient. Whole exome sequencing identified a homozygous missense variant in the adaptor protein (AP) complex 2 alpha-2 subunit (AP2A2) gene. Western blot analysis showed reduced levels of AP2A2 in patient-iPSC derived neuronal cells. Endocytosis of transferrin receptor (TfR) was decreased in patient-derived neurons. In addition, we observed increased axon initial segment length in patient-derived neurons. Xenopus tropicalis tadpoles with ap2a2 knockout showed cerebral edema and progressive seizures. Immunoprecipitation of the mutant human AP-2-appendage alpha-C construct showed defective binding to accessory proteins. We report AP2A2 as a novel genetic entity associated with HSP and provide functional data in patient-derived neuron cells and a frog model. These findings expand our understanding of the mechanism of HSP and improve the genetic diagnosis of this condition.

The Effect of Age and Comorbidities: Children vs. Adults in Their Response to SARS-CoV-2 Infection

While children have experienced less severe coronavirus disease (COVID-19) after SARS-CoV-2 infection than adults, the cause of this remains unclear. The objective of this study was to describe the humoral immune response to COVID-19 in child vs. adult household contacts, and to identify predictors of the response over time. In this prospective cohort study, children with a positive SARS-CoV-2 polymerase chain reaction (PCR) test (index case) were recruited along with their adult household contacts. Serum IgG antibodies against SARS-CoV-2 S1/S2 spike proteins were compared between children and adults at 6 and 12 months after infection. A total of 91 participants (37 adults and 54 children) from 36 families were enrolled. Overall, 78 (85.7%) participants were seropositive for anti-S1/S2 IgG antibody at 6 months following infection; this was higher in children than in adults (92.6% vs. 75.7%) (p = 0.05). Significant predictors of a lack of SARS-CoV-2 seropositivity were age ≥ 25 vs. < 12 years (odds ratio [OR] = 0.23, p = 0.04), presence of comorbidities (vs. none, adjusted OR = 0.23, p = 0.03), and immunosuppression (vs. immunocompetent, adjusted OR = 0.17, p = 0.02).

Snapshot of Anti-SARS-CoV-2 IgG Antibodies in COVID-19 Recovered Patients in Guinea.

Background: Because the regular vaccine campaign started in Guinea one year after the COVID-19 index case, the profile of naturally acquired immunity following primary SARS-CoV-2 infection needs to be deepened. Methods: Blood samples were collected once from 200 patients (90% of African extraction) who were recovered from COVID-19 for at least ~2.4 months (72 days), and their sera were tested for IgG antibodies to SARS-CoV-2 using an in-house ELISA assay against the Receptor Binding Domain (RBD) of the SARS-CoV-2 spike1 protein (RBD/S1-IH kit). Results: Results revealed that 73% of sera (146/200) were positive for IgG to SARS-CoV-2 with an Optical Density (OD) ranging from 0.13 to 1.19 and a median value of 0.56 (IC95: 0.51-0.61). The median OD value at 3 months (1.040) suddenly decreased thereafter and remained stable around OD 0.5 until 15 months post-infection. The OD median value was slightly higher in males compared to females (0.62 vs. 0.49), but the difference was not statistically significant (p-value: 0.073). In contrast, the OD median value was significantly higher among the 60-100 age group (0.87) compared to other groups, with a noteworthy odds ratio compared to the 0-20 age group (OR: 9.69, p-value: 0.044*). Results from the RBD/S1-IH ELISA kit demonstrated superior concordance with the whole spike1 protein ELISA commercial kit compared to a nucleoprotein ELISA commercial kit. Furthermore, anti-spike1 protein ELISAs (whole spike1 and RBD/S1) revealed higher seropositivity rates. Conclusions: These findings underscore the necessity for additional insights into naturally acquired immunity against COVID-19 and emphasize the relevance of specific ELISA kits for accurate seropositivity rates.

A LONG QT SYNDROME WITHOUT MANIFESTATION

Abstract A 66–year–old Caucasian woman presented for outpatient evaluation due to elevated blood pressure levels at home (approximately 220/120 mmHg) and a significant family history of long QT syndrome. The index case in the family appeared to be her sister, investigated following an ECG showing markedly prolonged QT interval and a family history of sudden cardiac death. The patient underwent genetic analysis, revealing a positive mutation in KCNQ1. She was currently on treatment with Levotiroxina for recently discovered hypothyroidism.The ECG showed sinus rhythm with a heart rate of 85 bpm, signs of left ventricular hypertrophy, particularly Sokolow (SV1 + RV6 70 mm) and Peguero Lo Presti (SD + SV4 50 mm). The QTc interval was 515 ms (Bazett). Echocardiography revealed severe left ventricular hypertrophy (SIVd 14 mm; PWd 12 mm; LVMi 128 g/m2; RWT 0.5) with normal overall systolic function (EF 60%). No significant valvular pathologies were observed, and the right ventricle appeared normal in size and function.The hypertrophy was attributed to uncontrolled severe arterial hypertension. However, the identification of a prolonged QT interval in a patient with a strong family component (Schwartz score 4, high probability) led to genetic testing, confirming a mutation in KCNQ1. As the patient was asymptomatic with a low risk of major arrhythmias over the next 5 years (1–2–3–LQTS–risk score 2.77%), she entered follow–up and received beta–blocker therapy, specifically nadolol, combined with other antihypertensive medications.This clinical case describes an entire family with LQTS1 (type 1) positive for KCNQ1 mutation, exhibiting phenotypic manifestations distinct from those reported in the literature. Notably, there was a prevalence in females, and the condition was incidentally discovered during a routine checkup conducted for unrelated reasons, without any history of major arrhythmias.Long QT syndrome (LQTS) is characterized by a prolonged QT interval, predisposing individuals to life–threatening arrhythmias leading to syncope and sudden death. Mutations in genes encoding ion channels account for 75% of LQTS cases. LQTS1, associated with a "loss–of–function" mutation in the KCNQ1 gene, represents one of the three genetic subtypes. LQTS1 typically manifests with arrhythmias in childhood, with a male predominance. Adrenergic triggers are crucial precipitants for arrhythmic events

UNPREDICTABLE IDENTIFICATION OF A TITIN MUTATION IN A YOUNG PATIENT PRESENTING WITH INFLAMMATORY CARDIOMYOPATHY

Abstract Case Presentation A 23 years old patient, affected by type 1 diabetes, presented with fever, dyspnea and bilateral peripheral edemas. In the last week he received antibiotic treatment for a persistent dry cough and sore throat, and became symptomatic for exertional dyspnea from three days. His mother died at the age of 40 for sudden cardiac death. Blood pressure and oxygen saturation were normal: the ECG showed sinus tachycardia with symmetric negative T waves in all precordial leads. High sensitivity troponin T was 0.01 mcg/L (normal value < 0.014 mcg/L). All remaining blood tests were normal, except for CRP that was slightly elevated. His echocardiogram revealed left ventricular (LV) remodelling and dilation, severely reduced LV ejection fraction (LVEF 20%) with global hypokinesia, more pronounced at the level of the anterior wall, interventricular septum and apex and a dilated right ventricle (RV) with reduced systolic function. Cardiac magnetic resonance (CMR) confirmed severe biventricular disfunction (LVEF 19%; RVEF 23%) and showed a small area of subepicardial inferior junctional late gadolinium enhancement (LGE). The patient underwent an endomyocardial biopsy that showed a lymphocytic virus–negative myocarditis. Given his known type 1 diabetes, steroid treatment was not considered and anakinra was started. The patient was discharged after two weeks with a slight amelioration of the LV function (LVEF 27%), on optimal heart failure therapy and anakinra. At six months he was in NYHA class II and CMR showed slight reduction in LV dimensions and improvement of the LV and RV function (LVEF 39%; RVEF 45%), with no changes in the LGE pattern. A genetic test was performed and revealed two titin gene mutations, both categorized as likely pathogenic (TTN c.[11831T>A]; c.[72510_72517delGACAAATG]), responsible for a genetic form of dilated cardiomyopathy. Conclusion The present case suggests that in young patients presenting with clinical or histological diagnosis of myocarditis, genetic testing for cardiomyopathies should be considered especially in presence of a positive family history for sudden death or an incomplete recovery of the LV function at follow–up. Identification of a gene mutation in these patients allows a more tailored risk stratification of the index case and a proper management of the entire family.

Rare Genetic Developmental Disabilities: Mabry Syndrome (MIM 239300) Index Cases and Glycophosphatidylinositol (GPI) Disorders.

The case report by Mabry et al. (1970) of a family with four children with elevated tissue non-specific alkaline phosphatase, seizures and profound developmental disability, became the basis for phenotyping children with the features that became known as Mabry syndrome. Aside from improvements in the services available to patients and families, however, the diagnosis and treatment of this, and many other developmental disabilities, did not change significantly until the advent of massively parallel sequencing. As more patients with features of the Mabry syndrome were identified, exome and genome sequencing were used to identify the glycophosphatidylinositol (GPI) biosynthesis disorders (GPIBDs) as a group of congenital disorders of glycosylation (CDG). Biallelic variants of the phosphatidylinositol glycan (PIG) biosynthesis, type V (PIGV) gene identified in Mabry syndrome became evidence of the first in a phenotypic series that is numbered HPMRS1-6 in the order of discovery. HPMRS1 [MIM: 239300] is the phenotype resulting from inheritance of biallelic PIGV variants. Similarly, HPMRS2 (MIM 614749), HPMRS5 (MIM 616025) and HPMRS6 (MIM 616809) result from disruption of the PIGO, PIGW and PIGY genes expressed in the endoplasmic reticulum. By contrast, HPMRS3 (MIM 614207) and HPMRS4 (MIM 615716) result from disruption of post attachment to proteins PGAP2 (HPMRS3) and PGAP3 (HPMRS4). The GPI biosynthesis disorders (GPIBDs) are currently numbered GPIBD1-21. Working with Dr. Mabry, in 2020, we were able to use improved laboratory diagnostics to complete the molecular diagnosis of patients he had originally described in 1970. We identified biallelic variants of the PGAP2 gene in the first reported HPMRS patients. We discuss the longevity of the Mabry syndrome index patients in the context of the utility of pyridoxine treatment of seizures and evidence for putative glycolipid storage in patients with HPMRS3. From the perspective of the laboratory innovations made that enabled the identification of the HPMRS phenotype in Dr. Mabry's patients, the need for treatment innovations that will benefit patients and families affected by developmental disabilities is clear.

Transcriptionally Active Human Papillomavirus Infection in a Minority of Esophageal Squamous Cell Carcinomas in North America.

The role of Human papillomavirus (HPV) infection in esophageal squamous cell carcinoma (ESCC) is a topic of ongoing debate. This study used two screening approaches to look for evidence of HPV infection in esophageal squamous cell carcinoma. We initially checked for HPV infection in a randomly selected group of 53 ESCC cases. We did not detect any tumors positive for high-risk HPV. However, during clinical practice, we identified an HPV-positive ESCC in the distal esophagus, which tested positive for HPV16. This index case was TP53 wild-type, as determined by next-generation DNA sequencing (NGS). Since TP53 mutations are rare in other HPV-driven cancers, we improved our screening method by limiting our screen to a subset of ESCC cases without TP53 mutations. A second screen of 95 ESCCs (from 93 patients) sequenced by NGS revealed an additional 7 ESCCs with TP53 wild-type status (7.3% of the total). Of the 7 cases, 2 cases were found to be high-risk HPV positive. Both patients also tested positive for circulating cell-free HPV DNA and had a complete response to neoadjuvant chemoradiation. The index patient had microscopic residual tumor following neoadjuvant therapy. The patient underwent adjuvant immunotherapy and remained disease free after 22 months of surveillance. This study affirms the transcriptionally active status of high-risk HPV in a minority of ESCC patients in North America.

Predictors of positive tuberculin skin test in neonates exposed to pulmonary tuberculosis.

Neonates are at risk of nosocomial tuberculosis (TB) infection from health care workers (HCWs) in neonatal care facilities, which can progress to severe TB diseases. Tuberculin skin test (TST) is commonly used for TB diagnosis, but its accuracy in neonates is influenced by various factors, including bacilli Calmette-Guérin (BCG) vaccination. This study aimed to identify predictors of positive TSTs in neonates exposed to HCWs with pulmonary TB. A retrospective observational study was conducted to compare the frequency of predictors between TST-positive and TST-negative neonates. Demographic, epidemiological, and clinical data of neonates exposed to TB, along with that of HCW and household contacts, were collected retrospectively through contact investigations with the Korean National TB Surveillance System (KNTSS) database. TSTs using 2 tuberculin units of purified protein derivative RT23 were performed on exposed neonates at the end of preventive TB treatment. Firth logistic regression was performed to identify predictors of TST positivity. Contact investigations revealed that 152 neonates and 54 HCWs were exposed to infectious TB index cases in 3 neonatal care facilities. Of 152 exposed neonates, 8 (5.3%) had positive TST results. Age of 6 days or more at the initial exposure is a statistically significant predictor of positive TST (Firth coefficient 2.1, 95% confidence interval 0.3-3.9, P = 0.024); BCG vaccination showed no statistical significance in both univariable and multivariable analysis. Sex, prematurity, exposure duration, duration from initial exposure to contact investigation, and isoniazid preventive treatment duration were not significant predictors. Age at the initial exposure is a significant predictor of positive TST in neonates exposed to active pulmonary TB. Given the complexities of TST interpretation, including false positives due to BCG vaccination, careful risk assessment is necessary for appropriate decision-making and resource allocation in the management of neonatal TB exposure.

Examining the feasibility of assisted index case testing for HIV case-finding: a qualitative analysis of barriers and facilitators to implementation in Malawi

BackgroundAssisted index case testing (ICT), in which health care workers take an active role in referring at-risk contacts of people living with HIV for HIV testing services, has been widely recognized as an evidence-based intervention with high potential to increase status awareness in people living with HIV. While the available evidence from eastern and southern Africa suggests that assisted ICT can be an effective, efficient, cost-effective, acceptable, and low-risk strategy to implement in the region, it reveals that feasibility barriers to implementation exist. This study aims to inform the design of implementation strategies to mitigate these feasibility barriers by examining “assisting” health care workers’ experiences of how barriers manifest throughout the assisted ICT process, as well as their perceptions of potential opportunities to facilitate feasibility.MethodsIn-depth interviews were conducted with 26 lay health care workers delivering assisted ICT in Malawian health facilities. Interviews explored health care workers’ experiences counseling index clients and tracing these clients’ contacts, aiming to inform development of a blended learning implementation package. Transcripts were inductively analyzed using Dedoose coding software to identify and describe key factors influencing feasibility of assisted ICT. Analysis included multiple rounds of coding and iteration with the data collection team.ResultsParticipants reported a variety of barriers to feasibility of assisted index case testing implementation, including sensitivities around discussing ICT with clients, privacy concerns, limited time for assisted index case testing amid high workloads, poor quality contact information, and logistical obstacles to tracing. Participants also reported several health care worker characteristics that facilitate feasibility (knowledge, interpersonal skills, non-stigmatizing attitudes and behaviors, and a sense of purpose), as well as identified process improvements with the potential to mitigate barriers.ConclusionsMaximizing assisted ICT’s potential to increase status awareness in people living with HIV requires equipping health care workers with effective training and support to address and overcome the many feasibility barriers that they face in implementation. Findings demonstrate the need for, as well as inform the development of, implementation strategies to mitigate barriers and promote facilitators to feasibility of assisted ICT.Trial registrationNCT05343390. Date of registration: April 25, 2022.

Evolution towards extremely high β-lactam resistance in Mycobacterium abscessus outbreak strains.

Treatment of Mycobacterium abscessus pulmonary disease requires multiple antibiotics including intravenous β-lactams (e.g., imipenem, meropenem). M. abscessus produces a β-lactamase (BlaMab) that inactivates β-lactam drugs but less efficiently carbapenems. Due to intrinsic and acquired resistance in M. abscessus and poor clinical outcomes, it is critical to understand the development of antibiotic resistance both within the host and in the setting of outbreaks. We compared serial longitudinally collected M. abscessus subsp. massiliense isolates from the index case of a CF center outbreak and four outbreak-related strains. We found strikingly high imipenem resistance in the later patient isolates, including the outbreak strain (MIC >512 μg/ml). The phenomenon was recapitulated upon exposure of intracellular bacteria to imipenem. Addition of the β-lactamase inhibitor avibactam abrogated the resistant phenotype. Imipenem resistance was caused by an increase in β-lactamase activity and increased bla Mab mRNA level. Concurrent increase in transcription of preceding ppiA gene indicated upregulation of the entire operon in the resistant strains. Deletion of the porin mspA coincided with the first increase in MIC (from 8 to 32 μg/ml). A frameshift mutation in msp2 responsible for the rough colony morphology, and a SNP in ATP-dependent helicase hrpA co-occurred with the second increase in MIC (from 32 to 256 μg/ml). Increased BlaMab expression and enzymatic activity may have been due to altered regulation of the ppiA-bla Mab operon by the mutated HrpA alone, or in combination with other genes described above. This work supports using carbapenem/β-lactamase inhibitor combinations for treating M. abscessus, particularly imipenem resistant strains.

The Incidence of Skin and Soft Tissue Infections in the United States and Associated Healthcare Utilization Between 2010 and 2020.

The number of patients with skin and soft tissue infections (SSTIs) in the United States appeared to be increasing well into the 21st century. However, no recent data have confirmed this trend. This retrospective, observational cohort study used claims data over 11 years (2010-2020) from Optum's de-identified Clinformatics Data Mart Database. SSTI episodes, complications, and comorbidities were identified using International Classification of Diseases codes. Annual SSTI incidence rates, proportions of recurrent SSTI, SSTI-associated deaths, and total costs were estimated. During the study period, 5.4 million patients experienced 9.1 million SSTI episodes, with an incidence of 77.5 (95% confidence interval, 77.4-77.5) per 1000 person-years of observation (PYO). Annual incidence did not change significantly over time. Overall incidence (per 1000 PYO) of SSTI episodes in patients without comorbidities was 32.1 (highest incidence was for previous SSTI [113.5]) versus much higher rates if comorbidities were present. Incidence rates (per 1000 PYO) of chronic ulcers increased over time from 11.3 to 18.2 (P < .0001) and complicated disease from 3.5 to 6.3 (P < .0001). Deaths occurring within 30 days post-SSTI hospitalization rose from 2.6% to 4.6% in 2020. Recurrences occurred in 26.3% of index cases. The mean cost of an SSTI episode was US$3334 (median US$190) and was highest for surgical site infections and chronic ulcers. The epidemiology of SSTI in the United States is changing and the disease burden is increasing despite stabilization in overall incidence. These data can inform identification of priority populations who could benefit from targeted interventions.

Algorithm for detection and screening of familial hypercholesterolemia in Lithuanian population

BackgroundFamilial hypercholesterolemia (FH) is one of the most common autosomal dominant diseases. FH causes a lifelong increase in low-density lipoprotein cholesterol (LDL-C) levels, which in turn leads to atherosclerotic cardiovascular disease. The incidence of FH is widely underestimated and undertreated, despite the availability and effectiveness of lipid-lowering therapy. Patients with FH have an increased cardiovascular risk; therefore, early diagnosis and treatment are vital. To address the burden of FH, several countries have implemented national FH screening programmes. The currently used method for FH detection in Lithuania is mainly based on opportunistic testing with subsequent cascade screening of index cases’ first-degree relatives.MethodsA total of 428 patients were included in this study. Patients with suspected FH are referred to a lipidology center for thorough evaluation. Patients who met the criteria for probable or definite FH according to the Dutch Lipid Clinic Network (DLCN) scoring system and/or had LDL-C > = 6.5 mmol/l were subjected to genetic testing. Laboratory and instrumental tests, vascular marker data of early atherosclerosis, and consultations by other specialists, such as radiologists and ophthalmologists, were also recorded.ResultsA total of 127/428 (30%) patients were genetically tested. FH-related mutations were found in 38.6% (n = 49/127) of the patients. Coronary artery disease (CAD) was diagnosed in 13% (n = 57/428) of the included patients, whereas premature CAD was found in 47/428 (11%) patients. CAD was diagnosed in 19% (n = 9/49) of patients with FH-related mutations, and this diagnosis was premature for all of them.ConclusionsMost patients in this study were classified as probable or possible FH without difference of age and sex. The median age of FH diagnosis was 47 years with significantly older females than males, which refers to the strong interface of this study with the LitHir programme. CAD and premature CAD were more common among patients with probable and definite FH, as well as those with an FH-causing mutation. The algorithm described in this study is the first attempt in Lithuania to implement a specific tool which allows to maximise FH detection rates, establish an accurate diagnosis of FH, excluding secondary causes of dyslipidaemia, and to select patients for cascade screening initiation more precisely.

Characteristics of droplet dispersion and interpersonal exposure in indoor and outdoor dining areas of urban street: Elementary numerical investigations

Indoor and outdoor dining areas are special spaces where people generally sit close and talk face-to-face for a long time (∼hour). Semi-open dining area is of popularity among them, one of the reason is the thoughts that outdoor dining area have experienced small infectious risks, even though this opinion has not been thoroughly validated yet. As a novelty, this study conducts CFD simulations to investigate droplet dispersion and face-to-face exposure risk of customers in the indoor and outdoor dining areas of typical street canyons (H/W = 1) by coupling indoor/outdoor airflows. Different scenarios are considered including index patient locations, the setting of the desk isolation board (DIB, HDIB = 0.6 m or 1.2 m), and the outdoor semi-open street roof (SSR).Results show that indoor dining spaces with single-sided ventilation experience one-order poorer ventilation (net escape velocity NEV∼0.036 m/s) and subsequently 10–200 times higher face-to-face droplet trap fraction than those in outdoor dining areas (NEV∼0.407 m/s, TF∼3–102 ppm). Indoor desk isolation board can decrease face-to-face TF by 50 %, but in outdoors, TF without desk-isolation board is 6.5 ppm for 50 μm droplet and this value changes little or slightly increases as HDIB is 0.6 m (∼8.9 ppm) or 1.2 m (∼7.7 ppm), indicating DIB seems not helpful to reduce airborne exposure risk in outdoors. Moreover, the setting of an outdoor semi-open street roof (SSR) may reduce NEV in the indoor or outdoor dining area by half or 90 % respectively. Therefore, SSR may raise indoor and outdoor customers' face-to-face exposure risk (e.g. TF) by hundreds of times and seventy times respectively.

Peculiar Pattern of Irritant Contact Dermatitis to Semecarpus anacardium

Abstract Semecarpus anacardium (Family: Anacardiaceae), is a frequently used medicinal plant in alternative medicine. There has been few case reports suggesting the role of marking nut extract in allergic contact dermatitis. Case one presented with vesicles coalescing to form bullae with surrounding necrotic epidermis accompanied by itching and burning sensation over nape of neck. He developed recurrent urticarial episodes post treatment. Case two reported similar lesions over beard region after 2 weeks of our index case in addition to diffuse erythematous maculopapular pruritic rash over upper chest, face and anterior shoulder. Case three, four and five reported with similar kind of lesions over various body parts. Case six presented with targetoid lesion with central bullae over upper torso. Case seven reported with bizarre lesions like splattering of chemical which were morphologically similar as the other cases, over left popliteal fossa and calf area. Our cases were from the same geographic area and were in the same profession. On evaluation of the pattern and morphology of lesions and careful investigation, it was concluded that it was an irritant reaction to Semicarpus nut extract which was supported by histopathology findings. On further probing, it was observed that the individuals inflicted the injury in order to avoid some strenuous work. All were evaluated and none of them were found to be suffering from any psychiatric ailment. We reported this case series because of unique morphological presentation which has not yet been reported in the literature to the best of our knowledge.

Clinical characteristics, imaging, and lung function among patients with persistent dyspnea of COVID-19: a retrospective observational cohort study.

The available medical literature on lung function and corresponding clinical characteristics among symptomatic survivors of Corona Virus Disease 2019 (long COVID) is sparse. Primary physicians referred patients who manifested persistent dyspnea months after their index case of infection to a designated clinic. Patients underwent symptom-driven, quality-of-life, physical, and focused respiratory [pulmonary function tests and computed tomography (CT) of the chest] evaluations and were followed over time. In this paper, we present our findings. Patients with abnormal CT imaging were more likely to be of advanced age and to have been hospitalized during their COVID-19 infection. Forced exhaled volume in the first second, forced vital capacity (FVC), total lung capacity, and diffusion capacity of carbon monoxide measurements were found to be significantly lower in patients with abnormal CT imaging. Multivariate regression of clinical characteristics uncovered a significant association between FVC, body mass index, history of hospitalization, and diabetes mellitus. In conclusion, longer-term studies will help further our understanding of the risk factors, disease course, and prognosis of long COVID patients.

Brainstem Chipmunk Sign: A Diagnostic Imaging Clue across All Subtypes of Alexander Disease.

While classic brain MR imaging features of Alexander disease have been well-documented, lesional patterns can overlap with other leukodystrophies, especially in the early stages of the disease or in milder phenotypes. We aimed to assess the utility of a new neuroimaging sign to help increase the diagnostic specificity of Alexander disease. A peculiar bilateral symmetric hyperintense signal on T2-weighted images affecting the medulla oblongata was identified in an index patient with type I Alexander disease. Subsequently, 5 observers performed a systematic MR imaging review for this pattern by examining 55 subjects with Alexander disease and 74 subjects with other leukodystrophies. Interobserver agreement was assessed by the κ index. Sensitivity, specificity, and receiver operating characteristic curves were determined. The identified pattern was present in 87% of subjects with Alexander disease and 14% of those without Alexander disease leukodystrophy (P < .001), 3 with vanishing white matter, 4 with adult polyglucosan body disease, and 3 others. It was found equally in both type I and type II Alexander disease (28/32, 88% versus 18/21, 86%; P = .851) and in subjects with unusual disease features (2/2). Sensitivity (87.3%; 95% CI, 76.0%-93.7%), specificity (86.5%; 95% CI, 76.9%-92.5%), and interobserver agreement (κ index = 0.82) were high. The identified pattern in the medulla oblongata, called the chipmunk sign due to its resemblance to the face of this rodent, is extremely common in subjects with Alexander disease and represents a diagnostic tool that can aid in early diagnosis, especially in subjects with otherwise atypical MR imaging findings and/or clinical features.

The associations of opioid and benzodiazepine prescriptions with injuries among US military service members.

Given the high rates of physical trauma and pain among service members, opioid-prescribing practices and use patterns have significant implications for the well-being of service members and can affect military medicine and personnel readiness. This study measured the association between prescribed opioid and benzodiazepine medications and subsequently reported injuries (accidental, alcohol and drug related, self-inflicted, and violence related) among active duty military members. Participants were service members who entered the military between January 1, 2005, and June 30, 2010. In a nested case-control design, we compared individuals with injuries to individuals without injuries with respect to their opioid and benzodiazepine prescriptions in the 30 days before the injury of an index case. We used a multiintercept, logistic regression model to compare coefficient estimates by injury type. Overall, approximately 17% of individuals with an injury and 4% of individuals without an injury had a recorded opioid prescription. Individuals with an injury of any type had greater odds of prior exposure to opioid prescriptions than controls. Although a dose-response effect was observed for all injury types, it reached a plateau sooner for natural or environmental accidents and self-inflicted injuries relative to alcohol-related and drug-related injuries, violence-related injuries, vehicle accidents, accidental falls, and other accidents. Benzodiazepine prescriptions were found in 3.5% of individuals with an injury and 0.5% of individuals without an injury. The association between benzodiazepine prescriptions and injuries was strongest for natural and environmental accidents.

Genetic Structure of Introduced Plasmodium vivax Malaria Isolates in Greece, 2015-2019.

Greece has been malaria-free since 1974, after an intense malaria control program. However, as Greece hosts migrant populations from P. vivax malaria-endemic countries, there is a risk of introducing the disease to specific vulnerable and receptive areas of the country. Knowledge of the genetic diversity of P. vivax populations is essential for understanding the dynamics of malaria disease transmission in a given region. We used nine highly polymorphic markers to genotype 124 P. vivax-infected archived DNA samples from human blood specimens referred to the NMRL from all over Greece throughout 2015-2019. The genotypic variability of the samples studied was noted, as they comprised several unique haplotypes, indicative of the importation of a large number of different P. vivax strains in the country. However, only a few events of local transmission were recorded. Genotyping revealed and confirmed the same clusters as those identified through epidemiological investigation. In only one introduction event was the index case found. No sustained/ongoing malaria transmissions in/between the studied regions or during consecutive years or additional foci of local transmission were observed. Genotyping is an important component in assisting malaria surveillance, as it provides information concerning the patterns of introduction and the effectiveness of implemented malaria control and elimination measures.