bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastrointestinal parasites diagnoses at the primary health care units: a comparative analysis of diagnostic abilities of parasitology staff technicians versus medical parasitologists in Ismailia, Egypt
Authors: Ali Ahmed Shahira Abdelaziz , Mohamed Samar Farag , Fouad Ahmed Mahmoud , Karanis Panagiotis
Published: July 2022

Background

This study aims to compare parasitology technicians (ParaTechs) with medical staff parasitologists (MedParas) in terms of diagnostic ability and to assess the actual occurrence of gastrointestinal parasites in selected faecal samples from primary health care units (PHCUs).

Methods

The study included five PHCU ParaTechs in the El-Kassassin rural area, evaluated using a scoring system for their knowledge, skills, practices and parasitology laboratory facilities. Seventy-five faecal samples previously examined for ova and parasites by ParaTechs were chosen for re-evaluation by MedParas.

Results

The most deficient ParaTechs-related factor was the parasitological knowledge, which scored 23.9% of the maximum score, while ParaTechs had acceptable levels of skills and practices, scored 60% and 61%, respectively. Compared with MedParas, false positive ParaTech diagnoses made up 8.8% of all negative samples, while false negative diagnoses made up 85.4% of all positive samples. ParaTechs underestimated the count or misidentified the type of parasites in one-third of the true positive samples. The overall rate of misdiagnosis among ParaTechs was 53.3% of all samples.

Conclusions

Regular ParaTech training, including culture and staining at parasitology labs, and collaboration between the Ministry of Health and Population and academic institutions are essential to increase ParaTechs diagnostic abilities.
Calonectria queenslandica: Causal Agent ofEucalyptusLeaf Blight in Southern China
Authors: Li WenWen , Chen ShuaiFei , Wingfield Michael J. , Duong Tuan A.
Published: July 2022

Calonectria leaf blight caused by Calonectria spp. is among the most serious diseases affecting the health and sustainability of Eucalyptus plantations in southern China. Recent outbreaks of this disease in GuangDong Province prompted a need to identify the species involved. Typical symptoms of Calonectria leaf blight were observed on 2-year-old Eucalyptus urophylla × E. grandis trees in a plantation in the ZhaoQing region. In total, 38 Calonectria isolates were collected from 32 diseased trees. All isolates were identified using DNA sequence analyses of the translation elongation factor 1-α (tef1), β-tubulin (tub2), calmodulin (cmdA), and histone H3 (his3) gene regions. Phylogenetic analyses revealed that Calonectria queenslandica was the dominant species, accounting for 81.6% of the isolates collected. Other species isolated included C. pseudoreteaudii (10.5%), C. reteaudii (5.3%), and C. aconidialis (2.6%). This is the first report of C. queenslandica in China and all isolates had identical sequences in all four gene regions. PCR amplification using primers targeting the MAT1-1-1 and MAT1-2-1 genes in all C. queenslandica isolates revealed that only the MAT1-2 idiomorph was present. The results suggest that C. queenslandica was introduced into the sampled area with very limited genetic diversity. Pathogenicity tests were conducted on two Eucalyptus genotypes widely planted in the GuangDong Province using isolates representing all species collected. The results showed that these species could all cause disease but the predominance of C. queenslandica on infected trees suggests that it is the major driver of the disease problem studied. Different Eucalyptus genotypes used in the pathogenicity tests differed in susceptibility to infection by the Calonectria spp. tested, providing opportunities to avoid leaf blight by deploying disease-tolerant planting stock.
Transcription factor E3 renal cell carcinoma presenting as secondary hypertension
Authors: Mukendi Alain Mwamba , Mataruka Gerald Tatenda , Nadimpalli Ramesh , Kasapato Tshisola Miji
Published: July 2022

Microphthalmia-associated transcription factor family (transcription factor E3 or transcription factor EB) translocation renal cell carcinomas (RCCs) are rare neoplasms. These renal neoplasms can be either asymptomatic and incidentally discovered on imaging or symptomatic, with the most common presenting symptoms being hematuria, pain, and abdominal mass, or paraneoplastic event. In conventional RCCs, hypertension is considered a risk factor and a possible paraneoplastic event, whereas, in translocation RCCs, prior exposure to cytotoxic chemotherapy is the only known risk factor, and hypertension as an isolated associated paraneoplastic event has never been reported. Interestingly, hypertension as the only presenting symptom in RCC is extremely rare. We report a case of transcription factor E3 positive RCC in a young adult presenting only with hypertension that normalized after radical nephrectomy. To the best of our knowledge, this is the first reported case of hypertension secondary to microphthalmia-associated transcription translocation RCC.
Mesenteric panniculitis, a rare entity presenting as (sub)acute intestinal obstruction: a case report
Authors: Paudyal Nabin , Shrestha Bijaya , Yadav Deepak
Published: July 2022

Mesenteric panniculitis (MP) is a rare condition. A few literatures have been published reporting MP. No prior case reports have been published from Nepal. We report 1 such case of MP mimicking an intestinal obstruction at our Center. A 79-year-old lady presented with complaints of diffuse abdominal pain associated with vomiting. X-ray abdomen showed multiple thickened and dilated small bowel loops. Ultrasound of the abdomen revealed prominent small bowel loops with sluggish peristalsis. A provisional diagnosis of intestinal obstruction was made. A contrast-enhanced computerized scan of the abdomen-pelvis showed diffuse, heterogeneous mesenteric fat stranding. She was started on oral prednisolone (40 mg once daily) and discharged on the fourth day. Her follow-up 2 weeks later was uneventful. The steroid was tapered gradually over the next week. With a wide spectrum of clinical manifestations, MP often poses diagnostic challenges to physicians. Lack of awareness of the disease may be associated with an increased disease burden to patients. MP should also be considered as a differential diagnosis when features of bowel obstruction are present.
Tumor response-speed heterogeneity as a novel prognostic factor in patients with mCRC
Authors: Liu Junjia , Wang Xuefeng , Sahin Ibrahim H. , Imanirad Iman , Felder Seth I. , Kim Richard D. , Xie Hao
Published: July 2022

Purpose

Differential tumor response to therapy is partially attributed to tumor heterogeneity. Additional efforts are needed to identify tumor heterogeneity parameters in response to therapy that are easily applicable in clinical practice. We aimed to describe tumor response-speed heterogeneity and evaluate its prognostic value in patients with metastatic colorectal cancer (mCRC).

Patients and Methods

Individual patient data from Amgen (NCT00364013) and Sanofi (NCT00305188; NCT00272051) trials were retrieved from Project Data Sphere. Patients in the Amgen 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX) arm were used to establish response-speed heterogeneity. Its prognostic value was subsequently validated in the Sanofi FOLFOX arms and the Amgen panitumumab + FOLFOX arm. Kaplan-Meier method and Cox proportional hazards models were used for survival analyses.

Results

Patients with high response-speed heterogeneity in the Amgen FOLFOX cohort had significantly shorter (P<0.001) median progression-free survival (PFS) of 7.27 months (95%CI 6.12–7.96 months) and overall survival (OS) of 16.0 months (95%CI 13.8–18.2 months) than patients with low response-speed heterogeneity with median PFS of 9.41 months (95%CI 8.75– 10.89 months) and OS of 22.4 months (95%CI 20.1–26.7 months), respectively. Tumor response-speed heterogeneity was a poor prognostic factor of shorter PFS (HR 4.17, 95%CI 2.49–6.99, P<0.001) and shorter OS (HR 2.57, 95%CI 1.64–4.01, P<0.001), after adjustment for other common prognostic factors. Comparable findings were found in the external validation cohorts.

Conclusion

Tumor response-speed heterogeneity to first-line chemotherapy was a novel prognostic factor associated with early disease progression and shorter survival in patients with mCRC.

Implications for Practice

Routine clinical decision making heavily relies on radiographic assessment of disease response to therapy. For patients with heterogeneous tumors, the degree and kinetics of individual tumor response to the same therapy can sometimes be vastly different. We explored a novel quantitative parameter to describe response-speed heterogeneity by utilizing individual patient data from previous clinical trials. This parameter was an independent prognostic factor associated with early disease progression and shorter survival. Complementary to existing molecular and radiographic tumor heterogeneity parameters, it may help practicing oncologists describe tumor response disparity and serve as a new prognostic factor for patients with mCRC.
Efficacy of a patient isolation hood in reducing exposure to airborne infectious virus in a simulated healthcare setting
Authors: Lee Leo Yi Yang , Landry Shane A , Jamriska Milan , Subedi Dinesh , Joosten Simon A , Barr Jeremy J , Brown Reece , Kevin Kevin , Schofield Robyn , Monty Jason , Subbarao Kanta , McGain Forbes
Published: July 2022

Background

Healthcare workers treating patients with SARS-CoV-2 are at risk of infection from patient-emitted virus-laden aerosols. We quantified the reduction of airborne infectious virus in a simulated hospital room when a ventilated patient isolation (McMonty) hood was in use.

Methods

We nebulised 109plaque forming units (PFU) of bacteriophage PhiX174 virus into a 35.1m3room with a hood active or inactive. The airborne concentration of infectious virus was measured by BioSpot-VIVAS and settle plates using plaque assay quantification on the bacterial hostEscherichia coli C. The particle number concentration (PNC) was monitored continuously using an optical particle sizer.

Results

Median airborne viral concentration in the room reached 1.41 × 105PFU.m-3with the hood inactive. Using the active hood as source containment reduced infectious virus concentration by 374-fold in air samples. This was associated with a 109-fold reduction in total airborne particle number escape rate. The deposition of infectious virus on the surface of settle plates was reduced by 87-fold.

Conclusions

The isolation hood significantly reduced airborne infectious virus exposure in a simulated hospital room. Our findings support the use of the hood to limit exposure of healthcare workers to airborne virus in clinical environments.

Lay summary

COVID-19 patients exhale aerosol particles which can potentially carry infectious viruses into the hospital environment, putting healthcare workers at risk of infection. This risk can be reduced by proper use of personal protective equipment (PPE) to protect workers from virus exposure. More effective strategies, however, aim to provide source control, reducing the amount of virus-contaminated air that is exhaled into the hospital room.

The McMonty isolation hood has been developed to trap and decontaminate the air around an infected patient. We tested the efficacy of the hood using a live virus model to mimic a COVID-19 patient in a hospital room. Using the McMonty hood reduced the amount of exhaled air particles in the room by over 109-times. In our tests, people working in the room were exposed to 374-times less infectious virus in the air, and room surfaces were 87-times less contaminated. Our study supports using devices like the McMonty hood in combination with PPE to keep healthcare workers safe from virus exposure at work.
The COVID-19 pandemic impact on continuity of care provision on rare brain diseases and on Ataxia, Dystonia and PKU. A scoping review protocol
Authors: Cannizzo Sara , Quoidbach Vinciane , Giunti Paola , Oertel Wolfgang , Pastores Gregory , Relja Maja , Turchetti Giuseppe
Published: July 2022

One of the most relevant challenges for healthcare providers during the COVID – 19 pandemic has been assuring the continuity of care to patients with complex health needs such as people living with rare diseases (RDs). The COVID–19 pandemic accelerated the healthcare sector’s digital transformation agenda. The delivery of telemedicine services instead of many face-to-face procedures has been expanded and, many healthcare services not directly related to COVID-19 treatments shifted online remotely. Many hospitals, specialist centres, patients and families started to use telemedicine because they were forced to. This trend could directly represent a good practice on how care services could be organized and continuity of care could be ensured for patients. If done properly, it could boast improved patient outcomes and become a post COVID-19 major shift in the care paradigm. There is a fragmented stakeholders spectrum, as many questions arise on: how is e-health interacting with ‘traditional’ healthcare providers; about the role of the European Reference Networks (ERNs); if can remote care retain a human touch and stay patient centric. Here, we outline a protocol for a scoping review that investigates this topic, focusing on continuity of care and novel methods (e.g., digital approaches) used to reduce the care disruption. This scoping review protocol was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) standards and will culminate in a narrative synthesis of evidence.
The association between dysnatraemia during hospitalisation and post COVID-19 mental fatigue
Authors: Salvato Gerardo , Inglese Elvira , Fazia Teresa , Crottini Francesco , Crotti Daniele , Valentini Federica , Palmas Giulio , Bollani Alessandra , Basilico Stefania , Gandola Martina , Gelosa Giorgio , Gentilini Davide , Bernardinelli Luisa , Stracciari Andrea , Scaglione Francesco , Agostoni Elio Clemente , Bottini Gabriella
Published: July 2022

Objective

Coronavirus disease 2019 (COVID-19) may induce short- and long-term cognitive failures after recovery, but the underlying risk factors are still a matter of debate. Identifying patients at the highest risk is now a research priority to prevent persistent symptoms after recovery. In this study, we investigated whether: (i) the odds of experiencing persistent cognitive failures may differ based on the patients’ disease course severity and sex; (ii) the patients’ electrolytic profile at the acute stage may represent a risk factor for persistent cognitive failures.

Methods

We analysed data from 204 patients suffering from COVID-19 and hospitalised during the first pandemic wave. According to the 7-point WHO-OS Scale, their disease course was classified as severe (if the patient needed ventilation) or mild (if they did not). We investigated the presence of persistent cognitive failures using a modified version of the Cognitive Failures Questionnaire, collected after hospital discharge, while electrolyte profiles were collected during hospitalisation. We explored our hypotheses via logistic regression models.

Results

Females who suffered from mild COVID-19 were more likely to report mental fatigue than those with severe COVID-19 (β= 0.29, 95%CI [0.06; 0.53], p= 0.01). Furthermore, they present a statistically significant risk effect of Na+ alteration at the acute phase on the odds of presenting persistent mental fatigue (β= 0.37, 95%CI [0.09; 0.64], p= 0.01).

Interpretation

These findings have important implications for the clinical management of COVID-19 hospitalised patients. Attention should be paid to potential electrolyte imbalances, mainly in females suffering from mild COVID-19.

Key Points

Question

Do disease severity and sex predict the risk of persistent cognitive failures in COVID-19 hospitalised survivors? Does electrolytic imbalance at the acute phase represent a risk factor for persistent cognitive failures after recovery?

Findings

Females who suffered from mild compared to severe COVID-19 had a higher risk of presenting persistent mental fatigue. In this group, dysnatraemia at the acute stage represented a significant risk factor on the odds of showing such a persistent cognitive failure after recovery.

Meaning

Sodium levels must be monitored and balanced during hospitalisation of females affected by mild COVID-19 to prevent mental fatigue among the possible short- and long-term effects.
Telomere length among Chinese oldest old
Authors: Yeung Suey S.Y. , Wang Xingyan , Ma Suk Ling , Chen Yangchao , Tsui Stephen Kwok Wing , Tang Nelson Leung Sang , Woo Jean
Published: July 2022

Introduction

Telomere length (TL) is generally regarded as a biomarker of aging. TL, which is influenced by sociodemographic factors, has been shown to be inversely associated with morbidity. However, most studies were examined in the youngest old and whether the findings can be extended to the oldest old is less clear. This study examined TL and its associated factors in Chinese oldest old in Hong Kong.

Methods

Follow-up data collected after 14 years from the baseline of the Mr. and Ms. Osteoporosis cohort were analyzed. A structured interview on sociodemographic factors and physical measurement was conducted. Frailty and sarcopenia status were respectively determined by Fried’s criteria and Asian Working Group for Sarcopenia definition. TL was measured by a molecular inversion probe - quantitative PCR (MIP-qPCR) assay and expressed as telomere / a single copy reference gene (T/S) ratio. Adjusted binary logistic regressions were used to examine the associations between TL and the presence of multimorbidity, age-related diseases, frailty and sarcopenia.

Results

Among 555 participants (mean age 83.6±3.8 years, 41.3% women), the mean T/S ratio was 1.01±0.20. Males had lower T/S ratio (0.97±0.20) compared with females (1.07±0.18) (p<0.001). A lower education level was related to a longer TL (p=0.016). Being a current smoker was related to a shorter TL (p=0.007). TL was not significantly different across categories of age, subjective socioeconomic status, drinking status, physical activity level and body mass index (p>0.05). There were no associations between TL and the presence of multimorbidity, diabetes, stroke, cardiovascular diseases, cognitive impairment, frailty and sarcopenia.

Conclusion

Among Chinese oldest old, males had shorter TL compared with females. TL was not associated with age-related diseases, frailty and sarcopenia in this age group. TL may not be a biological marker of aging among the oldest old.
Geographic and temporal trends in fentanyl-detected deaths in Connecticut, 2009-2019
Authors: Lu Haidong , Crawford Forrest W. , Gonsalves Gregg S. , Grau Lauretta E.
Published: July 2022

Purpose

Since 2012 fentanyl-detected fatal overdoses have risen from 4% of all fatal overdoses in Connecticut to 82% in 2019. We aimed to investigate the geographic and temporal trends in fentanyl-detected deaths in Connecticut during 2009-2019.

Methods

Data on the dates and locations of accidental/undetermined opioid-detected fatalities were obtained from Connecticut Office of the Chief Medical Examiner. Using a Bayesian space-time binomial model, we estimated spatiotemporal trends in the proportion of fentanyl-detected deaths.

Results

During 2009-2019, a total of 6,632 opioid deaths were identified. Among these, 3,234 (49%) were fentanyl-detected. The modeled spatial patterns suggested that opioid deaths in northeastern Connecticut had higher probability of being fentanyl-detected, while New Haven and its neighboring towns and the southwestern region of Connecticut, primarily Greenwich, had a lower risk. Model estimates also suggested fentanyl-detected deaths gradually overtook the preceding non-fentanyl opioid-detected deaths across Connecticut. The estimated temporal trend showed the probability of fentanyl involvement increased substantially since 2014.

Conclusion

Our findings suggest that geographic variation exists in the probability of fentanyl-detected deaths, and areas at heightened risk are identified. Further studies are warranted to explore potential factors contributing to the geographic heterogeneity and continuing dispersion of fentanyl-detected deaths in Connecticut.
Near point-of-care HIV viral load testing: Uptake and utilization in suburban Yangon, Myanmar
Authors: Tun Ni Ni , Smithuis Frank , Tun Nyan Lynn , Min Myo , Ma Hlaing Myo Ma , van Olmen Josefien , Lynen Lutgarde , Gils Tinne
Published: July 2022

Introduction

HIV viral load testing in resource-limited settings is often centralized, limiting access. Near point-of-care (POC) viral load testing was introduced in Myanmar in 2017. We assessed its uptake and utilization.

Methods

Routine program data from three HIV clinics of Medical Action Myanmar were used. Annual viral load uptake was cross-sectionally analysed in people living with HIV (PLHIV) on antiretroviral therapy (ART) initiated between July 2009-June 2019. Attrition at two years was assessed between PLHIV with different access to viral load testing with Kaplan-Meier analysis. For those eligible for a first viral load when near POC viral load became available, a viral load cascade was constructed. We used logistic regression to explore predictors of confirmed virological failure after a first high viral load.

Results

Among 5271 PLHIV who started ART between July 2009-December 2019, annual viral load uptake increased significantly after near POC was introduced. Attrition in the first two years after ART initiation was not different among those eligible for a first viral load before viral load was available, after centralized laboratory-based viral load, and after near POC viral load introduction. After introduction of near POC viral load, 92% (2945/3205) of eligible PLHIV received a first viral load, a median of 2.8 years (IQR: 1.4-4.4) after initiation. The delay was 3.7 years (IQR: 2.8-5.1) and 0.9 years (IQR: 0.6-1.4) in those becoming eligible before and after near POC viral load was available, respectively. Among those with a first viral load, 95% (2796/2945) were ≤1000 copies/ml. Eighty-four % (125/149) of those with a viral load >1000 copies/ml received enhanced adherence counselling and a follow up viral load, a median of 119 days (IQR: 95-167) after the first viral load. Virological failure was confirmed in 67% (84/125), and 82% (69/84) of them were switched to second-line ART. Nine-three % (64/69) among those switched were alive on ART at end of follow-up. Having a first viral load of ≥5000 copies/ml was associated with confirmed virological failure.

Conclusion

Near POC viral load testing enabled rapid scale-up of viral load testing in Myanmar. PLHIV with a high viral load were adequately managed.
The Association of Socioeconomic Status, the Concern for Catching Covid-19, and Anxiety Between Individuals with and without a Cancer History from a Cross-sectional Study
Authors: Zhang Xiaochen , Sasmal Sonya , Yu Mengda , Bernardo Brittany , Adeyanju Toyin , Paskett Electra D.
Published: July 2022

Background

COVID-19 has negative impacts on mental health in all populations. Individuals with a history of cancer have an increased risk of catching and having more severe symptoms of COVID-19 than the general public. The objective of this study was to examine how cancer history and concern for catching COVID-19 relate to anxiety.

Methods

This cross-sectional study is part of the “Impact of COVID-19 on Behaviors across the Cancer Control Continuum in Ohio” project conducted from June to November 2020. The sample consisted of 7012 participants who completed survey online, by phone, or by mail. Self-reported concern for catching COVID-19 and anxiety over the last 7 days were used. Linear and logistic regression models were performed to determine the association between demographics, cancer history, concern for catching COVID-19, and anxiety.

Results

In our study sample, most participants rated their concern for catching COVID-19 as moderately high or high (56%) and reported anxiety for one day or more (63%). Individuals with a cancer history were more likely to report moderate-high or high concern for catching COVID-19 (59% vs.54%, P<0.001) but less likely to report anxiety (58% vs. 67%, P<0.001) compared to those without a cancer history. Individuals with higher SES were less likely to report anxiety (middle vs. low SES: OR=0.68, 95%CI=0.59-0.79; high vs. low SES: OR=0.70, 95%CI=0.61-0.82). Additionally, increased concern for catching COVID-19 was associated with higher likelihood of reporting anxiety (moderate-low vs. low: OR=1.65, 95%CI=1.42-1.92; moderate-high vs. low: OR=2.98, 95%CI=2.53-3.50; high vs. low: OR=4.35, 95%CI=3.74-5.07).

Conclusions

Our findings suggest individuals with a cancer history reported higher concern for catching COVID-19. Higher concern for catching COVID was associated with anxiety. These findings indicate that healthcare providers should pay special attention to the different populations to reduce concerns for catching COVID-19 and provide strategies to improve mental health during a pandemic outbreak.

Funding

This study was supported by a supplement to The Ohio State University Comprehensive Cancer Center (OSUCCC) core support grant (P30 CA016058), and the OSUCCC The Recruitment, Intervention and Survey Shared Resource (RISSR)(P30 CA016058).The Ohio State University Center for Clinical and Translational Science grant support (National Center for Advancing Translational Sciences, Grant UL1TR001070) in publications relating to this project. This work was supported by the National Cancer Institute (F99CA253745 to X.Z.).
Promoting HIV care continuum outcomes among people who use drugs and alcohol: A systematic review of randomized trials published from 2011 to 2021
Authors: Pitpitan Eileen V. , Wiginton John Mark , Romero Raul Bejarano , Baker Dania Abu
Published: July 2022

Substance use remains a robust predictor of HIV infection, as well as a serious impediment to progress across the HIV care continuum for people living with HIV. As such, the careful design and implementation of interventions uniquely tailored to target substance use and HIV care behaviors remain paramount. A necessary step in these efforts is to understand the extent to which HIV care interventions have been efficacious in helping people who use substances progress across the HIV care continuum. Using PubMed and ProQuest databases, we performed a systematic review of randomized trials of HIV care continuum interventions among people who use substances published between 2011 and 2021, the treatment-as-prevention era. Existing systematic reviews and studies in which less than half of those sampled reported substance use were excluded. We identified ten studies (total N=5410; range: 210-1308), nine of which intentionally targeted substance-using populations. Four of these studies involved use of at least one of several substances, including alcohol, opioids, stimulants, and/or marijuana, among others; three involved injection drug use only; one involved methamphetamine use only; and one involved alcohol use only. One study targeted a population with incidental substance use, which involved use of alcohol, injection drug use, and non-injection drug use. Viral suppression was targeted in 8/10 studies, followed by uptake/initiation of antiretroviral therapy (ART; 6/10), ART adherence (6/10), retention to care (4/10), and linkage to care (3/10). For each outcome, intervention effects were found in roughly half of the studies in which a given outcome was assessed. Mediated (2/10) and moderated (2/10) effects were minimally examined. The diversity of substances used in and across studies, as well as other characteristics that varied across studies, prevented broad deductions or conclusions about the amenability of specific substances to intervention. Moreover, study quality was mixed due to varying attrition and assessment measures (self-report vs biological/clinical). More coordinated, comprehensive, and targeted efforts are needed to disentangle intervention effects on HIV care continuum outcomes among populations using diverse substances.
Sildenafil in Emergency Treatment of Biliary Colic: A pilot randomized controlled trial
Authors: Yakoot Mostafa
Published: July 2022

Background

Sildenafil was reported to have a strong inhibitory effect on both gallbladder contraction and biliary pressure of the Sphincter of Oddi. We hypothesized that a single oral dose of sildenafil might counteract the smooth muscle spasm and decrease the intra-ductal and sphincteric pressures to relieve pain of biliary colic and facilitate release of impacted stones.

Objectives

To assess the pain-relieving effect of 25 mg oral Sildenafil dose in comparison to an oral 20 mg ketorolac dose in adult patients presenting with acute biliary colic.

Methods

Twenty consecutive eligible patients presenting with moderate to severe biliary colic were randomly assigned to receive one Sildenafil 25 mg tablet or two ketorolac 10 mg oral tablets. A four point’s verbal rating scale (VRS) and 100 mm Visual pain analog scale (VPAS) of pain severity were measured before treatment then at 30 and 60 minutes after the dose intake.

Results

Treatment success, defined as reduction of VRS, 60 minutes after dose intake from moderate and severe to mild or none was similar (9/10) in both treatment groups. Significant reductions of VPAS at 30 and 60 minutes were noted in both groups. The reduction in VPAS after 60 minutes from dose intake was significantly greater in Sildenafil group (83.16%) than ketorolac group (79.34%) (p=0.033).

Conclusions

Single oral dose of sildenafil 25 mg might be safe and effective for relief of biliary colic. Further studies are needed to confirm its value particularly for patients who cannot tolerate or show inadequate response to NSAIDs or opiates.

Highlights

Sildenafil has a strong relaxing effect on the smooth muscles of gallbladder.

We tested the effect of sildenafil 25 mg oral dose on the relief biliary colic.

We found it at least comparable to 20 mg of the potent analgesic ketorolac.

We recommend further studies on impacted stones in the common bile duct.
Early Detection of SARS-CoV-2 Omicron BA.4/5 in German wastewater
Authors: Wilhelm Alexander , Schoth Jens , Meinert-Berning Christina , Bastian Daniel , Ciesek Sandra , Teichgräber Burkhard , Wintgens Thomas , Weber Frank-Andreas , Widera Marek
Published: July 2022

Wastewater-based SARS-CoV-2 epidemiology (WBE) has been established as an important tool to support individual testing strategies. Omicron sub-variants BA.4/5 have spread globally displacing the predeceasing variants. Due to the severe transmissibility and immune escape potential of BA.4/5, early monitoring was required to asses and implement countermeasures in time.

In this study, we monitored the prevalence of SARS-CoV-2 BA.4/5 at six municipal wastewater treatment plants (WWTPs) in the Federal State of North-Rhine-Westphalia (NRW, Germany) in May and June 2022. Initially, L452R-specific primers/probes originally designed for SARS-CoV-2 Delta detection were validated using inactivated authentic viruses and evaluated for their suitability to detect BA.4/5. Subsequently, the assay was used for RT-qPCR analysis of RNA purified from wastewater obtained twice a week at six WWTPs. The occurrence of L452R carrying RNA was detected in early May 2022 and the presence of BA.4/5 was confirmed by variant-specific single nucleotide polymorphism PCR (SNP-PCR) targeting E484A/F486V. Finally, the mutant fractions were quantitatively monitored by digital PCR confirming BA.4/5 as the majority variant by 5th June 2022.

In conclusions, the successive workflow using RT-qPCR, variant-specific SNP-PCR, and RT-dPCR demonstrates the strength of WBE as a versatile tool to rapidly monitor variant spreading independent of individual test capacities.
The human host response to monkeypox infection: a proteomic case series study
Authors: Wang Ziyue , Tober-Lau Pinkus , Farztdinov Vadim , Lemke Oliver , Schwecke Torsten , Steinbrecher Sarah , Muenzner Julia , Kriedemann Helene , Sander Leif Erik , Hartl Johannes , Mülleder Michael , Ralser Markus , Kurth Florian
Published: July 2022

Monkeypox (MPX) is caused by the homonymous orthopoxvirus (MPXV) known since the 1970s to occur at low frequency in West and Central Africa. Recently, the disease has been spreading quickly in Europe and the US. The rapid rise of MPX cases outside previously endemic areas and the different clinical presentation prompt for a better understanding of the disease, including the development of clinical tests for rapid diagnosis and monitoring. Here, using Zeno SWATH MS - a latest-generation proteomic technology - we studied the plasma proteome of a group of MPX patients with a similar infection history and clinical severity typical for the current outbreak. Moreover, we compared their proteomes to those of healthy volunteers and COVID-19 patients. We report that MPX is associated with a strong and characteristic plasma proteomic response and describe MPXV infection biomarkers among nutritional and acute phase response proteins. Moreover, we report a correlation between plasma protein markers and disease severity, approximated by the degree of skin manifestation. Contrasting the MPX host response with that of COVID-19, we find a range of similarities, but also important differences. For instance, Complement factor H-related protein 1 (CFHR1) is induced in COVID-19, but suppressed in MPX, reflecting the different role of the complement system in the two infectious diseases. However, the partial overlap between MPX and COVID-19 host response proteins allowed us to explore the repurposing of a clinically applicable COVID-19 biomarker panel assay, resulting in the successful classification of MPX patients. Hence, our results provide a first proteomic characterization of the MPX human host response based on a case series. The results obtained highlight that proteomics is a promising technology for the timely identification of disease biomarkers in studies with moderate cohorts, and we reveal a thus far untapped potential for accelerating the response to disease outbreaks through the repurposing of multiplex biomarker assays.
Assessing COVID-19 pandemic excess deaths in Brazil: years 2020 and 2021
Authors: Robles Colonia Saditt Rocio , Cardeal Lara Morena , de Oliveira Rogério Antonio , Trinca Luzia Aparecida
Published: July 2022

We estimated the impact of the COVID-19 pandemic on mortality in Brazil for 2020 and 2021 years. We used mortality data (2015–2021) from the Health Ministry, the Brazilian government, to fit linear mixed models for forecasting baseline deaths under non-pandemic conditions. An advantage of the linear mixed model is the flexibility to capture year-trend while dealing with the correlations among death counts over time. Following a specified model-building strategy, estimation of all-cause excess deaths at the country level and stratified by sex, age, ethnicity and region of residence, from March 2020 to December 2021. We also considered the estimation of excess deaths due to specific causes. The estimated all-cause excess deaths was 187 842 (95% PI: 164 122; 211 562, P-Score=16.1%) for weeks 10-53, 2020, and 441 048 (95% PI: 411 740; 470 356, P-Score=31.9%) for weeks 1-52, 2021. P-Score values ranged from 1.4% (RS, South) to 38.1% (AM, North) in 2020 and from 21.2% (AL and BA, Northeast) to 66.1% (RO, North) in 2021. Differences among men (18.4%) and women (13.4%) appeared in 2020 only, and the P-Score values were about 30% for both sexes in 2021. Except for youngsters (<20 years old), all adult age groups were badly hit, especially those from 40 to 79 years old. In 2020, the Indigenous+East Asian population had the highest P-Score (26.2%), and the Black population suffered the greatest impact (34.7%) in 2021. The pandemic impact had enormous regional heterogeneity and substantial differences according to socio-demographic factors, mainly during the first wave, showing that some population strata benefited from the social distancing measures when they could adhere to them. In the second wave, the burden was very high for all but extremely high for some, highlighting that our society must tackle the health inequalities experienced by groups of different socio-demographic status.
Projecting COVID-19 Cases and Subsequent Hospital Burden in Ohio
Authors: Khuda Bukhsh Wasiur R. , Bastian Caleb Deen , Wascher Matthew , Klaus Colin , Sahai Saumya Yashmohini , Weir Mark , Kenah Eben , Root Elisabeth , Tien Joseph H. , Rempala Grzegorz
Published: July 2022

As the Coronavirus 2019 (COVID-19) disease started to spread rapidly in the state of Ohio, the Ecology, Epidemiology and Population Health (EEPH) program within the Infectious Diseases Institute (IDI) at the Ohio State University (OSU) took the initiative to offer epidemic modeling and decision analytics support to the Ohio Department of Health (ODH). This paper describes the methodology used by the OSU/IDI response modeling team to predict statewide cases of new infections as well as potential hospital burden in the state.

The methodology has two components: 1) A Dynamic Survival Analysis (DSA)-based statistical method to perform parameter inference, statewide prediction and uncertainty quantification. 2) A geographic component that down-projects statewide predicted counts to potential hospital burden across the state. We demonstrate the overall methodology with publicly available data. A Python implementation of the methodology has been made available publicly.

Highlights

We present a novel statistical approach called Dynamic Survival Analysis (DSA) to model an epidemic curve with incomplete data. The DSA approach is advantageous over standard statistical methods primarily because it does not require prior knowledge of the size of the susceptible population, the overall prevalence of the disease, and also the shape of the epidemic curve.

The principal motivation behind the study was to obtain predictions of case counts of COVID-19 and the resulting hospital burden in the state of Ohio during the early phase of the pandemic.

The proposed methodology was applied to the COVID-19 incidence data in the state of Ohio to support the Ohio Department of Health (ODH) and the Ohio Hospital Association (OHA) with predictions of hospital burden in each of the Hospital Catchment Areas (HCAs) of the state.
Risk factors among Black and White COVID-19 patients from a Louisiana Hospital System, March, 2020 – August, 2021
Authors: Yu Qingzhao , Cao Wentao , Hamer Diana , Urbanek Norman , Straif-Bourgeois Susanne , Cormier Stephania , Ferguson Tekeda , Richmond-Bryant Jennifer
Published: July 2022

Objectives

To investigate relationships between race and COVID-19 hospitalizations, intensive care unit (ICU) admissions, and mortality over time and which characteristics, may mediate COVID-19 associations.

Methods

We analyzed hospital admissions, ICU admissions, and mortality among positive COVID-19 cases within the ten-hospital Franciscan Ministries of Our Lady Health System around the Mississippi River Industrial Corridor in Louisiana over four waves of the pandemic from March 1, 2020 – August 31, 2021. Associations between race and each outcome were tested, and multiple mediation analysis was performed to test if other demographic, socioeconomic, or air pollution variables mediate the race-outcome relationships.

Results

Race was associated with each outcome over the study duration and during most waves. Early in the pandemic, hospitalization, ICU admission, and mortality rates were greater among Black patients, but as the pandemic progressed these rates became greater in White patients. However, Black patients were still disproportionately represented in these measures. Age was a significant mediator for all outcomes across waves, while comorbidity and emissions of naphthalene and chloroprene acted as mediators for the full study period.

Conclusions

The role of race evolved throughout the pandemic in Louisiana, but Black patients bore a disproportionate impact. Naphthalene and chloroprene air pollution partially explained the long-term associations. Our findings imply that air pollution might contribute to the increased COVID-19 hospitalizations and mortality among Black residents in Louisiana but likely do not explain most of the effect of race.

What is already known on this topic

Early in the pandemic, there was evidence of disparities in COVID-19 cases, hospitalizations, intensive care unit (ICU) admissions, and mortality due to race. Studies were emerging to indicate that strength of these relationships was waning over time.

What this study adds

This study tests relationships between race and hospitalizations, ICU admissions, and mortality and finds that Black patients continue to be disproportionately represented, although that inequity diminished over time. This study, the first to use multiple mediation analysis to study COVID-19 associations, suggests that the relationship between race and health outcome can be explained by mediators including age and, to a lesser extent, comorbidity and air pollution.

How this study might affect research, practice or policy

This study supports the need for healthcare resources to be available to Louisiana’s communities of color, for policy to support increased access to health care in the Industrial Corridor region, and for policy to support the reduction of air pollution emissions to disproportionately impacting the health of the Industrial Corridor’s communities of color.
Immune Heterogeneity and Epistasis Explain Punctuated Evolution of SARS-CoV-2
Authors: Nielsen Bjarke Frost , Li Yimei , Sneppen Kim , Simonsen Lone , Viboud Cécile , Levin Simon A. , Grenfell Bryan T.
Published: July 2022

Identifying drivers of viral diversity is key to understanding the evolutionary as well as epidemiological dynamics of the COVID-19 pandemic. Using rich viral genomic data sets, we show that periods of steadily rising diversity have been punctuated by sudden, enormous increases followed by similarly abrupt collapses of diversity. We introduce a mechanistic model of saltational evolution with epistasis and demonstrate that these features parsimoniously account for the observed temporal dynamics of inter-genomic diversity. Our results provide support for recent proposals that saltational evolution may be a signature feature of SARS-CoV-2, allowing the pathogen to more readily evolve highly transmissible variants. These findings lend theoretical support to a heightened awareness of biological contexts where increased diversification may occur. They also underline the power of pathogen genomics and other surveillance streams in clarifying the phylodynamics of emerging and endemic infections. In public health terms, our results further underline the importance of equitable distribution of up-to-date vaccines.
Border-associated macrophages transventricularly infiltrate the early embryonic cerebral wall to differentiate into microglia
Authors: Hattori Yuki , Kato Daisuke , Murayama Futoshi , Koike Sota , Naito Yu , Kawaguchi Ayano , Wake Hiroaki , Miyata Takaki
Published: July 2022

The relationships between microglia and macrophages, especially their lineage segregation outside the yolk sac, have been recently explored, providing a model in which a conversion from macrophages seeds microglia during brain development. However, spatiotemporal evidence to support such microglial seeding and to explain how it occurs has not been obtained. By cell tracking via slice culture, intravital imaging, and Flash tag-mediated labeling, we found that a group of intraventricular macrophages belonging to border-associated macrophages (BAMs), which were abundantly observed along the inner surface of the mouse cerebral wall at embryonic day 12, frequently entered the brain wall. Immunohistochemistry of the tracked cells showed that postinfiltrative BAMs acquired microglial properties while losing a macrophage phenotype. We also found that the intraventricular BAMs were supplied transepithelially from the roof plate. Thus, this study demonstrates that the “roof plate→ventricle→cerebral wall” route is an essential path for microglial colonization into the embryonic mouse brain.
Multiscale functional connectivity patterns of the aging brain learned from rsfMRI data of 4,259 individuals of the multi-cohort iSTAGING study
Authors: Zhou Zhen , Srinivasan Dhivya , Li Hongming , Abdulkadir Ahmed , Nasrallah Ilya , Wen Junhao , Doshi Jimit , Erus Guray , Mamourian Elizabeth , Bryan Nick R. , Wolk David A. , Beason-Held Lori , Resnick Susan M. , Satterthwaite Theodore D. , Davatzikos Christos , Shou Haochang , Fan Yong ,   the ISTAGING Consortium
Published: July 2022

To learn multiscale functional connectivity patterns of the aging brain, we built a brain age prediction model of functional connectivity measures at seven scales on a large fMRI dataset, consisting of resting-state fMRI scans of 4259 individuals with a wide age range (22 to 97 years, with an average of 63) from five cohorts. We computed multiscale functional connectivity measures of individual subjects using a personalized functional network computational method, harmonized the functional connectivity measures of subjects from multiple datasets in order to build a functional brain age model, and finally evaluated how functional brain age gap correlated with cognitive measures of individual subjects. Our study has revealed that functional connectivity measures at multiple scales were more informative than those at any single scale for the brain age prediction, the data harmonization significantly improved the brain age prediction performance, and harmonization in the tangent space worked better than in the original space. Moreover, brain age gap scores of individual subjects derived from the brain age prediction model were significantly correlated with clinical and cognitive measures. Overall, these results demonstrated that multiscale functional connectivity patterns learned from a large-scale multi-site rsfMRI dataset were informative for characterizing the aging brain and the derived brain age gap was associated with cognitive and clinical measures.
Amyloid beta peptides (Aβ) from Alzheimer’s disease neuronal secretome induce endothelial activation in a human cerebral microvessel model
Authors: Shin Yu Jung , Evitts Kira M. , Jin Solhee , Howard Caitlin , Sharp-Milgrom Margaret , Young Jessica E. , Zheng Ying
Published: July 2022

In Alzheimer’s disease (AD), secretion and deposition of amyloid beta peptides (Aβ) have been associated with blood-brain barrier dysfunction. However, the role of Aβ in endothelial cell (EC) dysfunction remains elusive. Here we investigated AD mediated EC activation by studying the effect of Aβ secreted from human induced pluripotent stem cell-derived cortical neurons (hiPSC- CN) harboring a familial AD mutation (Swe+/+) on human brain microvascular endothelial cells (HBMECs) in 2D and 3D perfusable microvessels. We demonstrated that increased Aβ levels in Swe+/+ conditioned media (CM) led to stress fiber formation and upregulation of genes associated with endothelial inflammation and immune-adhesion. Perfusion of Aβ-rich Swe+/+ CM induced acute formation of von Willebrand factor (VWF) fibers in the vessel lumen, which was attenuated by reducing Aβ levels in CM. Our findings suggest that Aβ can trigger rapid inflammatory and thrombogenic responses within cerebral microvessels, which may exacerbate AD pathology.