The midgut epithelium of mosquitoes adjusts cell proliferation and endoreplication to respond to physiological challenges.

BACKGROUND: Hematophagous mosquitoes transmit many pathogens that cause human diseases. Pathogen acquisition and transmission occur when female mosquitoes blood feed to acquire nutrients for reproduction. The midgut epithelium of mosquitoes serves as the point of entry for transmissible viruses and parasites. RESULTS: We studied midgut epithelial dynamics in five major mosquito vector species by quantifying PH3-positive cells (indicative of mitotic proliferation), the incorporation of nucleotide analogs (indicative of DNA synthesis accompanying proliferation and/or endoreplication), and the ploidy (by flow cytometry) of cell populations in the posterior midgut epithelium of adult females. Our results show that the epithelial dynamics of post-emergence maturation and of mature sugar-fed guts were similar in members of the Aedes, Culex, and Anopheles genera. In the first three days post-emergence, ~ 20% of cells in the posterior midgut region of interest incorporated nucleotide analogs, concurrent with both proliferative activity and a broad shift toward higher ploidy. In mature mosquitoes maintained on sugar, an average of 3.5% of cells in the posterior midgut region of interest incorporated nucleotide analogs from five to eight days post-emergence, with a consistent presence of mitotic cells indicating constant cell turnover. Oral bacterial infection triggered a sharp increase in mitosis and nucleotide analog incorporation, suggesting that the mosquito midgut undergoes accelerated cellular turnover in response to damage. Finally, blood feeding resulted in an increase in cell proliferation, but the nature and intensity of the response varied by mosquito species and by blood source (human, bovine, avian or artificial). In An. gambiae, enterocytes appeared to reenter the cell cycle to increase ploidy after consuming blood from all sources except avian. CONCLUSIONS: We saw that epithelial proliferation, differentiation, and endoreplication reshape the blood-fed gut to increase ploidy, possibly to facilitate increased metabolic activity. Our results highlight the plasticity of the midgut epithelium in mosquitoes' physiological responses to distinct challenges.

Relationship between cognitive reserve, brain volume, and neuropsychological performance in amnestic and nonamnestic MCI.

Cognitive Reserve (CR) is a theoretical construct that influences the onset and course of cognitive and structural changes that occur with aging and mild cognitive impairment (MCI). There is a paucity of research that examines the relationship of CR and brain volumes in amnestic (aMCI) and nonamnestic (naMCI) separately. This study is a retrospective chart review of MCI patients who underwent neuropsychological evaluation and brain MRI with NeuroReader™ (NR). NR is an FDA-cleared software that standardizes MRI volumes to a control sample. Classifications of aMCI and naMCI were based on Petersen criteria. CR was measured as education, occupation, and word reading. Data analysis included bivariate correlations between CR, neuropsychological test scores, and NR-brain volumes by MCI subtype. The Benjamini-Hochberg method corrected for multiple comparisons. The sample included 91 participants with aMCI and 41 with naMCI. Within naMCI, positive correlations were observed between CR and whole brain volume, total gray matter, bifrontal, left parietal, left occipital, and bilateral cerebellum. Within aMCI, no significant correlations were observed between CR and brain volumes. Positive correlations with CR were observed in language, attention, and visual learning in both aMCI and naMCI groups. The current study adds to the minimal literature on CR and naMCI. Results revealed that CR is associated with volumetrics in naMCI only, though cognitive findings were similar in both MCI groups. Possible explanations include heterogeneous disease pathologies, disease stage, or a differential influence of CR on volumetrics in MCI. Additional longitudinal and biomarker studies will better elucidate this relationship.

A Gamified Social Media-Based Head and Neck Radiology Education Initiative of the American Society of Head and Neck Radiology: Viewership and Engagement Trends at 3 Years.

BACKGROUND AND PURPOSE: Social media has made inroads in medical education. We report the creation and 3-year (2018-2021) longitudinal assessment of the American Society of Head and Neck Radiology Case of the Week (#ASHNRCOTW), assessing viewership, engagement, and impact of the coronavirus disease 2019 (COVID-19) pandemic on this Twitter-based education initiative. MATERIALS AND METHODS: Unknown cases were tweeted from the American Society of Head and Neck Radiology account weekly. Tweet impressions (number of times seen), engagements (number of interactions), and new followers were tabulated. A social media marketing platform identified worldwide distribution of Twitter followers. Summary and t test statistics were performed. RESULTS: #ASHNRCOTW was highly visible with 2,082,280 impressions and 203,137 engagements. There were significantly greater mean case impressions (9917 versus 6346), mean case engagements (1305 versus 474), case engagement rates (13.06% versus 7.76%), mean answer impressions (8760 versus 5556), mean answer engagements (908 versus 436), answer engagement rates (10.38% versus 7.87%), mean total (case + answer) impressions (18,677 versus 11,912), mean total engagements (2214 versus 910), and total engagement rates (11.79% versus 7.69%) for cases published after the pandemic started (all P values < .001). There was a significant increase in monthly new followers after starting #ASHNRCOTW (mean, 134 versus 6; P < .001) and significantly increased monthly new followers after the pandemic started compared with prepandemic (mean, 178 versus 101; P = .003). The American Society of Head and Neck Radiology has 7564 Twitter followers throughout 130 countries (66% outside the United States). CONCLUSIONS: Social media affords substantial visibility, engagement, and global outreach for radiology education. #ASHNRCOTW viewership and engagement increased significantly during the COVID-19 pandemic.

Methotrexate pneumonitis in a patient with gestational trophoblastic neoplasia.

Methotrexate, an immunomodulatory agent used for a wide variety of indications, can cause pulmonary toxicity in the form of pneumonitis, organising pneumonia, pulmonary fibrosis, pleural effusion, pulmonary infections or lymphoproliferative disease. We report a case of methotrexate pneumonitis in a patient with gestational trophoblastic neoplasia. The diagnosis of methotrexate pneumonitis is challenging, as the signs and symptoms can be caused by intercurrent infection, concomitant medications or an underlying disease condition. A high index of suspicion is required for diagnosis. Management consists of drug discontinuation and steroids in patients with respiratory failure.

Radio-Pathomic Maps of Cell Density Identify Brain Tumor Invasion beyond Traditional MRI-Defined Margins.

BACKGROUND AND PURPOSE: Currently, contrast-enhancing margins on T1WI are used to guide treatment of gliomas, yet tumor invasion beyond the contrast-enhancing region is a known confounding factor. Therefore, this study used postmortem tissue samples aligned with clinically acquired MRIs to quantify the relationship between intensity values and cellularity as well as to develop a radio-pathomic model to predict cellularity using MR imaging data. MATERIALS AND METHODS: This single-institution study used 93 samples collected at postmortem examination from 44 patients with brain cancer. Tissue samples were processed, stained with H&E, and digitized for nuclei segmentation and cell density calculation. Pre- and postgadolinium contrast T1WI, T2 FLAIR, and ADC images were collected from each patient's final acquisition before death. In-house software was used to align tissue samples to the FLAIR image via manually defined control points. Mixed-effects models were used to assess the relationship between single-image intensity and cellularity for each image. An ensemble learner was trained to predict cellularity using 5 × 5 voxel tiles from each image, with a two-thirds to one-third train-test split for validation. RESULTS: Single-image analyses found subtle associations between image intensity and cellularity, with a less pronounced relationship in patients with glioblastoma. The radio-pathomic model accurately predicted cellularity in the test set (root mean squared error = 1015 cells/mm2) and identified regions of hypercellularity beyond the contrast-enhancing region. CONCLUSIONS: A radio-pathomic model for cellularity trained with tissue samples acquired at postmortem examination is able to identify regions of hypercellular tumor beyond traditional imaging signatures.

A Study of Adrenal Insufficiency in Hemodynamically Stable Patients with Cirrhosis.

Adrenal insufficiency (AI) is well entrenched in medical constraints like septic shock, critically ill and multi-morbid hemodynamically unstable patients but its exact prevalence or differences in the cases of chronic liver disease (CLD) at variable grades of severity has recently gained momentum. The eventuality of AI propounding in stable compensated and decompensated cirrhosis without sepsis or in early and late stages of liver desecration are the existing lacunae in popular literature that this study aims to address. MATERIAL: A prospective, analytical study was conducted from March 2021 to December 2021 encompassing 100 hemodynamically stable patients with cirrhosis without infection, admitted at SMS Medical College, Jaipur, who were assessed clinically, biochemically and for adrenal functions. Adrenal insufficiency was defined on multivariable approach including basal 8am cortisol levels, followed by giving 250mcg synthetic adrenocorticotrophic hormone IM injection and retaking serum cortisol levels post-hourly interval to delineate peak and delta cortisol variables. All samples were processed by chemoluminiscence based method on fully automatic immunoassay analyser. OBSERVATION: The study comprised 81 males and 19 females with the mean age being 45.4±12.92 years, with CLD etiology concentrating substantially around alcohol consumption (71%). Viral comorbidities viz. HBV, HCV, both viral and alcohol related and miscellaneous causes were documented in 23, 10, 14 and 12 patients respectively. AI surfaced in 38% patients with CLD being statistically significant with p< 0.001. Inclusively, 10.5% patients with Child-Turcotte-Pugh (CTP) class A, 57.89% with CTP class B and 31.57% cases with CTP class C developed adrenal insufficiency. No statistical differences were found in age, sex; mean arterial pressure, heart rate, HDL, cirrhosis etiology, degree of alcohol consumption and manifestations of portal hypertension between patients with or without AI. For prudence, serum albumin levels were lower (p<0.5) with INR raised (p<0.33) in patients with AI than their counterparts. However, multivariate analysis revealed no direct independent adrenal insufficiency predictor. ROC curve showed that the CTP score may be a good predictor for AI in liver cirrhosis patients as supplemented by significant negative correlations found between CTP score and peak cortisol levels (p=0.001). CONCLUSION: Adrenal insufficiency found frequent even in stable cirrhotic patients form an integral division of the CLD spectra and worsening glucocorticoid levels should be periodically assessed in such patients for preventing parallel comorbidities.

Preliminary method for profiling volatile organic compounds in breath that correlate with pulmonary function and other clinical traits of subjects diagnosed with cystic fibrosis: a pilot study.

Cystic fibrosis (CF) is characterized by chronic respiratory infections which progressively decrease lung function over time. Affected individuals experience episodes of intensified respiratory symptoms called pulmonary exacerbations (PEx), which in turn accelerate pulmonary function decline and decrease survival rate. An overarching challenge is that there is no standard classification for PEx, which results in treatments that are heterogeneous. Improving PEx classification and management is a significant research priority for people with CF. Previous studies have shown volatile organic compounds (VOCs) in exhaled breath can be used as biomarkers because they are products of metabolic pathways dysregulated by different diseases. To provide insights on PEx classification and other CF clinical factors, exhaled breath samples were collected from 18 subjects with CF, with some experiencing PEx and others serving as a baseline. Exhaled breath was collected in Tedlar bags during tidal breathing and cryotransferred to headspace vials for VOC analysis by solid phase microextraction coupled to gas chromatography-mass spectrometry. Statistical significance testing between quantitative and categorical clinical variables displayed percent-predicted forced expiratory volume in one second (FEV1pp) was decreased in subjects experiencing PEx. VOCs correlating with other clinical variables (body mass index, age, use of highly effective modulator treatment (HEMT), and the need for inhaled tobramycin) were also explored. Two volatile aldehydes (octanal and nonanal) were upregulated in patients not taking the HEMT. VOCs correlating to potential confounding variables were removed and then analyzed by regression for significant correlations with FEV1pp measurements. Interestingly, the VOC with the highest correlation with FEV1pp (3,7-dimethyldecane) also gave the lowestp-value when comparing subjects at baseline and during PEx. Other VOCs that were differentially expressed due to PEx that were identified in this study include durene, 2,4,4-trimethyl-1,3-pentanediol 1-isobutyrate and 5-methyltridecane. Receiver operator characteristic curves were developed and showed 3,7-dimethyldecane had higher ability to classify PEx (area under the curve (AUC) = 0.91) relative to FEV1pp values at collection (AUC = 0.83). However, normalized ΔFEV1pp values had the highest capability to distinguish PEx (AUC = 0.93). These results show that VOCs in exhaled breath may be a rich source of biomarkers for various clinical traits of CF, including PEx, that should be explored in larger sample cohorts and validation studies.

Knowledge assessment and outcomes of otolaryngology practice amidst the COVID-19 pandemic in a busy ENT department.

INTRODUCTION: Otolaryngology health personnel are at high risk of acquiring COVID-19 disease and, hence, are likely to have high stress levels. This study was designed to evaluate the feedback of otolaryngology healthcare workers in ENT departments who are managing patients in the coronavirus pandemic. METHODS: A questionnaire focused on all aspects of healthcare delivery was completed by otolaryngology healthcare workers. RESULTS: The findings, based on statistical analyses, included high stress levels and inadequate disease-related information in these workers. CONCLUSIONS: Healthcare authorities need to take care of issues related to mental health in healthcare professionals in addition to spreading awareness about safe practices. Further studies are needed to continuously monitor feedback from personnel as the coronavirus pandemic unravels in the future.

Geographical variation in case fatality rate and doubling time during the COVID-19 pandemic.

Case fatality rate (CFR) and doubling time are important characteristics of any epidemic. For coronavirus disease 2019 (COVID-19), wide variations in the CFR and doubling time have been noted among various countries. Early in the epidemic, CFR calculations involving all patients as denominator do not account for the hospitalised patients who are ill and will die in the future. Hence, we calculated cumulative CFR (cCFR) using only patients whose final clinical outcomes were known at a certain time point. We also estimated the daily average doubling time. Calculating CFR using this method leads to temporal stability in the fatality rates, the cCFR stabilises at different values for different countries. The possible reasons for this are an improved outcome rate by the end of the epidemic and a wider testing strategy. The United States, France, Turkey and China had high cCFR at the start due to low outcome rate. By 22 April, Germany, China and South Korea had a low cCFR. China and South Korea controlled the epidemic and achieved high doubling times. The doubling time in Russia did not cross 10 days during the study period.

Study of Spectrum of Chromosomal Rearrangements in Recurrent Pregnancy Loss.

INTRODUCTION: Recurrent pregnancy losses (RPLs) are seen in up to 15-20% of all clinically recognized pregnancies, 1-2% of women in general population. Repeated losses are seen in 5-10% of women. The prevalence of chromosomal rearrangements is 6.65% in couples with repeated pregnancy losses. Two to 4% of RPL are associated with parental balanced reciprocal and Robertsonian translocations. MATERIALS AND METHODS: The study was conducted at a tertiary care hospital in New Delhi, and in total, 204 couples with RPL enrolled in the study. RESULTS: In total, 4490 couples presented to the obstetric clinic, of which 204 (4.5%) couples had repeated pregnancy losses. Cytogenetic analysis was done in 198 couples. Out of total 198 patients, 14 patients (7.1%) had cytogenetic alterations. Most common aberrations observed were structural rearrangements, of which reciprocal translocations were more common. In our study cohort, all the couples had maternal age of ≤ 35 years and all the alterations were seen either in mother or in both parents. DISCUSSION: Our study highlights that cytogenetic alterations not only are common in first trimester miscarriages, but are an important event in miscarriages presenting at later period of gestation and in young mothers as well.

Support of nursing homes in infection management varies by US State Departments of Health.

BACKGROUND: In many countries, healthcare-associated infections (HAIs) are problematic in long-term aged care living facilities. In the United States (US), HAIs occur frequently in nursing homes (NHs). Identifying effective practices for state Departments of Health (DOHs) to help NHs improve infection prevention and control and reduce HAIs is necessary. AIM: As a first step, the objective was to systematically examine and catalogue the variations in state intentions and activities related to HAI prevention in NHs. METHODS: An environmental scan of state DOH websites, HAI plans, and HAI state infographics was conducted. Data were collected on 16 items across three domains: (1) intentions to reduce HAIs in NHs, (2) actions to reduce HAIs in NHs, and (3) website usability. FINDINGS: State infection control support for NHs varied widely. Most states (92%) mentioned NHs in their HAI plans and 76% included NHs in their infographic. Half has an HAI prevention advisory council, while one-third had a state HAI prevention collaborative. Only 57% of HAI plans that mentioned NHs included training materials on HAI reduction. The most common training available was on antibiotic stewardship. CONCLUSION: Many US states have room for improvement in the support they provide NHs regarding infection prevention and control. Specific areas of improvement include: (1) increased provision of training materials on HAI reduction, (2) focusing training materials on common HAIs, and (3) NH engagement in collaboratives aimed at HAI reduction. More research is needed linking DOH activities to resident outcomes.

Patient experiences and health system responsiveness among internal migrants: A nationwide study in 13 Indian cities.

OBJECTIVE: To report various components of health system responsiveness among poor internal migrants who availed the government health facilities in 13 Indian cities. MATERIALS AND METHODS: Cluster random sampling was used to select 50,806 migrant households, of which 14,263 households avail the government health facility in last six months. In addition, 5072 women, who sought antenatal care and 3946 women who had delivery in government health facility during last six months were also included. Data on different domains of health system responsiveness were collected using an interviewer-administered questionnaire, developed based on the World Health Survey of WHO. RESULTS: Of the eight domains of responsiveness, namely, autonomy, communication, confidentiality, dignity, choice, quality of basic facilities, prompt attention and access to family and community, seven domains, except the 'choice', are assessed, and they are moderate. Only about 30% of participants said that doctor discussed on treatment options (autonomy). And 50-60% of participants said positively for questions of clarity of communication. About 59% of participants acknowledged the confidentiality. Not more than 40% of participants said they were treated with dignity, and privacy is respected (dignity). The responses to quality basic amenities, prompt attention and access to family and community domains are fairly satisfactory. CONCLUSIONS: This study has implications as many urban poor, including migrants do not utilize the services of public healthcare facilities. Hence, a responsive health system is required. There should be a policy in place to train and orient healthcare workers on some of the domains of health system responsiveness.

Outcomes after intensity-modulated compared with 3-dimensional conformal radiotherapy with chemotherapy for squamous cell carcinoma of the anal canal.

Purpose: We report our institution's treatment techniques, disease outcomes, and complication rates after radiotherapy for the management of anal canal carcinoma with intensity-modulated radiotherapy (imrt) and concurrent chemotherapy relative to prior cases managed with 3-dimensional conformal radiotherapy (3D-crt). Methods: In a retrospective review of the medical records of 21 patients diagnosed with biopsy-proven stage i (23%), stage ii (27%), or stage iii (50%) squamous-cell carcinoma of the anal canal treated with curative chemotherapy and imrt between July 2009 and December 2014, patient outcomes were determined. Results for patients treated with 3D-crt by the same group were previously reported. The median initial radiation dose to the pelvic and inguinal nodes at risk was 45 Gy (range: 36-50.4 Gy), and the median total dose, including local anal canal primary tumour boost, was 59.4 Gy (range: 41.4-61.2 Gy). Patients received those doses over a median of 32 fractions (range: 23-34 fractions). Chemotherapy consisted of 2 cycles of concurrent fluorouracil-cisplatin (45%) or fluorouracil-mitomycin C (55%). Results: Median follow-up was 3.1 years (range: 0.38-6.4 years). The mean includes a patient who died of septic shock at 38 days. The 3-year rates of overall survival, metastasis-free survival, locoregional control, and colostomy-free survival were 95%, 100%, 100%, and 100% respectively. No patients underwent abdominoperitoneal resection after chemoradiotherapy or required diverting colostomy during or after treatment. Those outcomes compare favourably with the previously published series that used 3D-crt with or without brachytherapy in treating anal canal cancers. Of the 21 patients in the present series, 10 (48%) experienced acute grade 3, 4, or 5 toxicities related to treatment. Conclusions: The recommended use of imrt with concurrent chemotherapy as an improvement over 3D-crt for management of anal canal carcinoma achieves a high probability of local control and colostomy-free survival without excessive risk for acute or late treatment-related toxicities.

Oncological benefits of postoperative radiotherapy in node-negative early stage cancer of the oral cavity with isolated perineural invasion.

Perineural invasion has been widely regarded as a poor prognostic factor in cancer of the oral cavity, but adjuvant treatment based only on this is still debatable. We have made an effort to address the question in a retrospective analysis of data from 2009-15 of patients with early node-negative cancers of the oral cavity. Patients with perineural invasion were divided into those who were treated with radiotherapy and those who were not. The records of a total of 169 patients were analysed, and 118 were given adjuvant radiotherapy and 51 were not. The median (range) duration of follow up was 45 (26-86) months. Of 169 patients, 47 (28%) developed recurrence, 28 in the treated, and 19 in the untreated, group. There was a significant disease-free survival benefit for adjuvant treatment (p = 0.047) but no overall survival benefit (p = 0.54). We conclude that adjuvant radiotherapy should be considered for patients with perineural invasion, even in early cancers of the oral cavity.

Effect of prior dengue infection on severity and outcome of Japanese encephalitis.

Japanese encephalitis (JE) virus and dengue virus are closely related flaviviruses but interaction between them is scarcely studied in humans. The objective of this study was to compare the outcome of JE patients who are positive and negative for dengue IgG antibodies. Patients of acute encephalitis syndrome (AES) fulfilling predecided inclusion and exclusion criteria underwent a detailed standardized workup incorporating JE IgM testing in cerebrospinal fluid (CSF) or serum. Dengue IgG in serum was tested in all. Outcomes and clinical features were compared between JE patients who were dengue IgG positive and negative in hospital and after 3 months. A total of 182 patients of JE were enrolled over 3 seasons. After excluding equivocal cases, hospital outcome was compared between 105 dengue IgG-positive and 50 dengue IgG-negative patients. Dengue IgG-positive patients had a significantly better outcome (relative risk 1.4; 95% confidence interval 1.1-1.8). On follow-up after 3 months, again, outcome was significantly better among 95 dengue IgG-positive patient than 47 dengue IgG-negative patients (relative risk 1.3; 95% confidence interval 1.01-1.8). Presence of pre-existing dengue IgG antibodies in JE patients is associated with improved outcomes.

Solifenacin is effective and well tolerated in patients with neurogenic detrusor overactivity: Results from the double-blind, randomized, active- and placebo-controlled SONIC urodynamic study.

AIMS: To investigate the effect on urodynamics of 4 weeks treatment with solifenacin succinate in patients with neurogenic detrusor overactivity (NDO) due to multiple sclerosis (MS) or spinal cord injury (SCI). METHODS: SONIC was a prospective, multicenter, double-blind, phase 3b/4 study investigating the efficacy and safety of solifenacin 10 mg in patients with NDO due to MS or SCI. Patients (n = 189) were randomized to placebo or active treatment (solifenacin 5 mg, 10 mg or oxybutynin hydrochloride 15 mg) for 4 weeks, after a 2-week, single-blind, placebo run-in period. The primary endpoint was change in maximum cystometric capacity (MCC) from baseline to end of treatment. The primary analysis compared solifenacin 10 mg versus placebo; all other comparisons were considered secondary. Secondary endpoints included changes in urodynamic parameters, patient-reported outcomes, and safety assessments. RESULTS: In the primary analysis, solifenacin 10 mg significantly improved mean change from baseline MCC versus placebo (P < 0.001) and was associated with improvements in bladder volume at first contraction and at first leak as well as detrusor pressure at first leak. Similar results were obtained for oxybutynin versus placebo. Patient perception of bladder condition significantly improved with solifenacin 10 mg versus placebo (P = 0.041). There was a clear improvement in quality of life (QoL) in the solifenacin arms versus placebo. The overall incidence of adverse events was low. CONCLUSIONS: In patients with NDO due to MS and SCI, 4 weeks of treatment with solifenacin 10 mg improved urodynamic variables and QoL versus placebo and was well tolerated. Neurourol. Urodynam. 36:414-421, 2017. © 2015 Wiley Periodicals, Inc.