bluuebunny/crossref_metadata_2025 huggingface dataset:
Negative Pressure Wound Therapy for Extremity Open Wound Management: A Review of the Literature
Authors: Van Rysselberghe Noelle L. , Gonzalez Christian A. , Calderon Christian , Mansour Adam , Oquendo Yousi A. , Gardner Michael J.
Published: August 2022

Negative pressure wound therapy (NPWT) with reticulated open cell foam is used commonly in orthopaedic trauma, particularly in the management of complex open fracture wounds. This article reviews the literature to date regarding this adjunctive treatment, particularly in regard to removal of infectious material, temporary management of wounds pending soft tissue reconstruction, combat wounds, and over split-thickness skin grafts. Mechanism of action is also reviewed, including stabilization of the wound environment, edema control, macrodeformation, and microdeformation effects. Use of NPWT as an adjunct in management of open fractures along with operative debridement, systemic antibiotics, and early soft tissue reconstruction are the highest yield interventions for managing open fracture wounds with infection. NPWT as an adjunct therapy in the protocol for open fractures seems to add additional clinical benefit for patients with severe open fracture wounds not amenable to primary, immediate closure.
Adult Trauma Patients With Thoracolumbar Injury Classification and Severity Score of 4
Authors: Naftchi Alexandria F. , Vazquez Sima , Spirollari Eris , Carpenter Austin B. , Ng Christina , Zeller Sabrina , Feldstein Eric , Rawanduzy Cameron , Das Ankita , Gabriele Christian , Gandhi Ronan , Stein Alan , Frid Ilya , Dominguez Jose F. , Hanft Simon J. , Houten John K. , Kinon Merritt D.
Published: August 2022

Study Design:

Systematic review.

Objective:

Evaluate characteristics of patients with thoracolumbar injury classification and severity (TLICS) score of 4 (To4) severity traumatic thoracolumbar injury.

Summary of Background Data:

The TLICS score is used to predict the need for operative versus nonoperative management in adult patients with traumatic thoracolumbar injury. Ambiguity exists in its application and score categorization.

Methods:

A systematic review of the literature was performed. The databases of MEDLINE, Embase, Web of Science, and Cochrane Review were queried. Studies included adults with traumatic thoracolumbar injury with assigned TLICS score and description of management strategy.

Results:

A total of 16 studies met inclusion criteria representing 1911 adult patients with traumatic thoracolumbar injury. There were 503 (26.32%) patients with To4, of which 298 (59.24%) were operative. Studies focusing on the thoracolumbar junction and AO Type A fracture morphology had To4 patient incidences of 11.15% and 52.94%, respectively. Multiple studies describe better quality of life, pain scores, and radiographic outcomes in To4 who underwent operative treatment patients.

Conclusion:

To4 injuries are more commonly AO Type A and located in the thoracolumbar junction in adult patients with traumatic thoracolumbar injury. Despite ambiguous recommendations regarding treatment provided by TLICS, outcomes favor operative intervention in this subset of traumatic thoracolumbar injury patients.
The Addition of a Temporary Intramedullary K-wire to Facilitate Plating for Metacarpal Fractures
Authors: Huang Chi-Han , Lo I-Ning , Wang Jung-Pan
Published: August 2022

Open reduction internal fixation with plate fixation is commonly used in treating metacarpal fractures to facilitate early rehabilitation. However, it is sometimes challenging to maintain a satisfactory 3-dimensional alignment during the plating process. We present a method using a temporary centrally placed intramedullary k-wire to maintain a fundamental stability for reduction of metacarpal fractures. This method facilitates the plating process and simplifies the open reduction internal fixation of the metacarpal fractures.
Beyond ibrutinib: novel BTK inhibitors for the treatment of chronic lymphocytic leukemia
Authors: Perutelli Francesca , Montalbano Maria Chiara , Boccellato Elia , Coscia Marta , Vitale Candida
Published: August 2022

Purpose of the review

Ibrutinib was the first Bruton tyrosine kinase inhibitor (BTKi) approved for clinical use, contributing to a dramatic change in the treatment landscape of chronic lymphocytic leukemia (CLL). This review provides an overview of next-generation BTKi that have been recently approved or are being investigated for the treatment of CLL, specifically highlighting differences and similarities compared to ibrutinib.

Recent findings

Acalabrutinib presented comparable response rates to ibrutinib with lower rates of adverse events and is currently approved for the treatment of CLL. Zanubrutinib displayed excellent response rates with a lower incidence of BTKi-related adverse events, but major rates of neutropenia, and its approval is awaited. With the aim of overcoming drug resistance, noncovalent BTKi have been developed. Of all the explored agents to date, pirtobrutinib has shown promising results with manageable toxicities.

For the treatment of CLL, several effective therapeutic strategies to target BTK are or will soon be available: these drugs present different safety profiles, thus making it possible to tailor the treatment choice according to patient's characteristics. Importantly, noncovalent BTKi will provide a therapeutic chance also for those relapsed/refractory CLL patients who are BTKi-resistant and are considered an unmet clinical need.
SURGICAL OUTCOMES OF VASOPROLIFERATIVE RETINAL TUMORS' REFRACTORY TO NONINVASIVE THERAPIES
Authors: Mares Virginia , Veloso Carlos E. , Pulido Jose S. , Nehemy Marcio B.
Published: August 2022

Purpose:

To evaluate the outcomes of surgical treatment of refractory vasoproliferative retinal tumors (VPTs) and its complications.

Methods:

Clinical charts of all patients diagnosed with VPTs who underwent surgical treatment from 2005 to 2020 were reviewed. Clinical features, surgical techniques, and outcomes were evaluated.

Results:

From 25 eyes of 23 patients with VPTs, 17 (68%) eyes underwent surgical intervention to treat tumor activity and associated complications including epiretinal membrane (n = 10, 59%), retinal detachment (n = 8, 47%), and vitreous hemorrhage (n = 3, 18%). All eyes underwent pars plana vitrectomy with endolaser/cryotherapy to control tumor activity and to treat associated complications. Three cases required tumor resection. At the end of follow-up (mean 55.4 months, range 2–305 months), no eye presented tumor activity or retinal detachment after one or two surgeries. There was no epiretinal membrane recurrence. The mean baseline best-corrected visual acuity was 1.2 ± 0.7 logMAR, and the mean final best-corrected visual acuity was 0.7 ± 0.6 logMAR (P < 0.05). The best-corrected visual acuity improved two or more lines in 12 (70.5%) eyes at the end of follow-up.

Conclusion:

In this series of patients with large active VPTs, surgical intervention allowed control of the tumor activity in all patients and provided overall satisfactory anatomic and functional outcomes.
A PIGMENTED FUNDUS LESION WITH PSEUDOHYPOPYON AND SUBRETINAL FLUID RESEMBLING UNILATERAL RETINAL PIGMENT EPITHELIUM DYSGENESIS
Authors: Krohn Jørgen , Vorren Alietha C.Y.
Published: August 2022

Purpose:

To describe multimodal imaging findings in a patient with a rare, symptomatic fundus lesion arising from the retinal pigment epithelium.

Methods:

Case report.

Results:

A 36-year-old woman presented with photopsia in her left eye. Funduscopy revealed an 8-mm × 7-mm, dark brown lesion at the level of the retinal pigment epithelium inferior to the macula. The lesion had an irregular, cauliflower-like border and a light grey subretinal pseudohypopyon. On fundus autofluorescence, the lesion was markedly hypoautofluorescent with an irregular hyperautofluorescent margin. It was generally hyopofluorescent on fluorescein angiography and moderately hypofluorescent on indocyanine green angiography. Spectral-domain optical coherence tomography revealed a fine layer of subretinal fluid over the entire lesion, thinning of the outer retinal layers with loss of photoreceptors, and an irregular retinal pigment epithelium. Multiple drusen-like subretinal deposits were located along the lesion margin, and inferiorly, the pseudohypopyon appeared as a hyperreflective subretinal mass. During 3 years of follow-up, her symptoms remained unchanged and fundus photography showed minimal enlargement of the lesion.

Conclusion:

Multimodal imaging findings of a solitary pigmented retinal pigment epithelium lesion with pseudohypopyon and subretinal fluid are shown. The lesion may represent an atypical variant of unilateral retinal pigment epithelium dysgenesis.
Firefighter Well-Being Defined and Operationalized at the Organizational and Worker Level
Authors: Kling Hannah E. , Maldonado Luisa , St George Sara M. , Brannan Debi , Murphy Lauren A. , Schaefer Solle Natasha , Kobetz Erin N. , Caban-Martinez Alberto J.
Published: August 2022

Objective

The aim of the study is to define and explore organizational- and worker-level factors of firefighter well-being.

Methods

Qualitative data were collected using interviews and focus group sessions among 17 career firefighters across 4 fire departments. Interviews were recorded and transcribed, and a general inductive approach was used to code similar concepts into themes.

Results

Firefighters defined well-being as being content with oneself and being able to balance ones’ emotional, mental, and physical health. Themes contributing to firefighter well-being include the nature of the job, the influence of others, and physical health. Subthemes mapping to themes include dealing with trauma, compartmentalizing work and home life, coworkers and station culture, the role of superiors on attitudes and practices, being a reliable firefighter, and lack of sleep.

Conclusions

Career firefighters describe well-being as a holistic approach to balancing emotional, mental, and physical health.
Bronchoalveolar Lavage (BAL) and Pathologic Assessment of Electronic Cigarette or Vaping Product Use-associated Lung Injury (EVALI)
Authors: Harry-Hernandez Salem , Thiboutot Jeffrey , Wahidi Momen M. , Giovacchini Coral X. , De Cardenas Jose , Meldrum Catherine , Los Jenna G. , Illei Peter B. , Shojaee Samira , Eissenberg Thomas , DiBardino David , Giannini Heather , Maldonado Fabien , Roller Lance , Yarmus Lonny B. , Kapp Christopher M.
Published: August 2022

Background:

E-cigarette or vaping-use related acute lung injury (EVALI) is a spectrum of radiographic and histologic patterns consistent with acute to subacute lung injury. However, limited data exist characterizing bronchoalveolar lavage (BAL) findings. The goal of this study is to further define the pathologic findings from BAL and biopsy samples of subjects with EVALI across 7 institutions.

Methods:

A multicentered registry of patients admitted with EVALI who underwent flexible bronchoscopy with BAL+/−transbronchial biopsy from July 2019 to April 2021 was compiled for retrospective evaluation from 7 academic institutions throughout the United States. Radiographic and cytopathologic findings and frequencies were correlated with the substance vaped.

Results:

Data from 21 subjects (42.9% women) who were predominantly White (76.2%) with a median age of 25 years (range, 16 to 68) with EVALI were included in this study. Sixteen patients (76.2%) reported use of tetrahydrocannabinol; the remainder used nicotine. BAL was performed in 19 of the 21 subjects, and transbronchial lung biopsy was performed in 7 subjects. BAL findings revealed neutrophilic predominance (median, 59.5%, range, 3.1 to 98) in most cases. Ten BAL samples demonstrated pulmonary eosinophilia ranging from 0.2% to 49.1% with one subject suggesting a diagnosis of acute eosinophilic pneumonia associated with the use of e-cigarettes. Lipid-laden macrophages were noted in 10 of 15 reports (66.7%). Transbronchial biopsy most frequently demonstrated patterns of organizing pneumonia (57.1%).

Conclusion:

EVALI-associated BAL findings typically demonstrate a spectrum of nonspecific inflammatory changes, including neutrophilia, lipid-laden macrophages, and in some cases eosinophilia.
Transcutaneous electrical stimulation in obstructive sleep apnoea: current developments and concepts of the TESLA-home programme
Authors: Nasser Ebrahim , Ratneswaran Deeban , Alsharifi Abdulaziz , Williams Adrian J. , Steier Joerg
Published: August 2022

Purpose of review

Obstructive sleep apnoea (OSA) is a highly prevalent condition affecting about 1 billion people worldwide. The first line therapy for most patients with OSA is continuous positive airway pressure (CPAP) therapy. However, there are significant limitations with long-term adherence to CPAP therapy, which may be as low as 30–60%.

Recent finding

Electrical stimulation of the hypoglossal nerve has been studied in recent years. It achieves upper airway patency by causing a contraction of the genioglossus muscle, the strongest dilator of the upper airway, and by maintaining its neuromuscular tone in the asleep patient with OSA. Electrical stimulation can be delivered invasively, hypoglossal nerve stimulation (HNS), and noninvasively, transcutaneous electrical stimulation in OSA (TESLA). However, randomised controlled trials, the STAR and the TESLA trial, have provided promising results on efficacy and safety of the methods.

Patient and public involvement underlines the interest in TESLA and HNS and highlights the need to provide non-CPAP therapeutic options to those who may find it difficult to cope with first line therapies. The relatively low costs and the favourable safety profile of the TESLA approach provide the chance to offer this treatment to patients with OSA following further development of the evidence.
Caregiver stress and social determinants of health in key populations: immigrant parents, parents of children with medical complexity, and adolescent parents
Authors: Smiley Yael , Silberholz Elizabeth , Bekele ElShadey , Brodie Nicola
Published: August 2022

Purpose of review

To examine the five domains of social determinants of health – economic stability, education access, healthcare access and quality, neighborhood and built environment, and social and community context – and how these relate to caregiver stress in under-resourced populations.

Recent findings

Socioeconomic and family factors are increasingly understood as drivers of child health. Caregiver stress can impact family stability and child wellbeing. Immigrant parents, caregivers of children with medical complexity, and adolescent parents experience stressors due to the unique needs of their families. These groups of parents and caregivers also face various challenges identified as social determinants of health. Interventions to mitigate these challenges can promote resilience, care coordination, and community-based supports.

Current research describes caregiver stress in key populations, how caregiver stress affects children, and approaches to minimize and mitigate these effects. Pediatric providers can implement best practices to support families who are navigating stress due to caregiving and social determinants of health.
Characteristics and Outcomes of Critically Ill Children With Multisystem Inflammatory Syndrome
Authors: Snooks Kellie , Scanlon Matthew C. , Remy Kenneth E. , Shein Steven L. , Klein Margaret J. , Zee-Cheng Janine , Rogerson Colin M. , Rotta Alexandre T. , Lin Anna , McCluskey Casey K. , Carroll Christopher L.
Published: August 2022

Objectives:

To characterize the prevalence of pediatric critical illness from multisystem inflammatory syndrome in children (MIS-C) and to assess the influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain on outcomes.

Design:

Retrospective cohort study.

Setting:

Database evaluation using the Virtual Pediatric Systems Database.

Patients:

All children with MIS-C admitted to the PICU in 115 contributing hospitals between January 1, 2020, and June 30, 2021.

Measurements and Main Results:

Of the 145,580 children admitted to the PICU during the study period, 1,338 children (0.9%) were admitted with MIS-C with the largest numbers of children admitted in quarter 1 (Q1) of 2021 (n = 626). The original SARS-CoV-2 viral strain and the D614G Strain were the predominant strains through 2020, with Alpha B.1.1.7 predominating in Q1 and quarter 2 (Q2) of 2021. Overall, the median PICU length of stay (LOS) was 2.7 days (25–75% interquartile range [IQR], 1.6–4.7 d) with a median hospital LOS of 6.6 days (25–75% IQR, 4.7–9.3 d); 15.2% received mechanical ventilation with a median duration of mechanical ventilation of 3.1 days (25–75% IQR, 1.9–5.8 d), and there were 11 hospital deaths. During the study period, there was a significant decrease in the median PICU and hospital LOS and a decrease in the frequency of mechanical ventilation, with the most significant decrease occurring between quarter 3 and quarter 4 (Q4) of 2020. Children admitted to a PICU from the general care floor or from another ICU/step-down unit had longer PICU LOS than those admitted directly from an emergency department.

Conclusions:

Overall mortality from MIS-C was low, but the disease burden was high. There was a peak in MIS-C cases during Q1 of 2021, following a shift in viral strains in Q1 of 2021. However, an improvement in MIS-C outcomes starting in Q4 of 2020 suggests that viral strain was not the driving factor for outcomes in this population.
Proton Pump Inhibitor Use and Associated Infectious Complications in the PICU: Propensity Score Matching Analysis
Authors: Goyer Isabelle , Lacotte Edouard , Montreuil Julien , Thibon Pascal , Briant Anaïs R. , Dupont Claire , Parienti Jean-Jacques , Brossier David
Published: August 2022

OBJECTIVES:

We aimed to evaluate the association between proton pump inhibitor (PPI) exposure and nosocomial infection (NI) during PICU stay.

DESIGN:

Propensity score matched analysis of a single-center retrospective cohort from January 1, 2017, to December 31, 2018.

SETTING:

Tertiary medical and surgical PICU in France.

PATIENTS:

Patients younger than 18 years old, admitted to the PICU with a stay greater than 48 hours.

INTERVENTION:

Patients were retrospectively allocated into two groups and compared depending on whether they received a PPI or not.

MEASUREMENTS AND MAIN RESULTS:

Seven-hundred fifty-four patients were included of which 231 received a PPI (31%). PPIs were mostly used for stress ulcer prophylaxis (174/231; 75%), but upper gastrointestinal bleed risk factors were rarely present (18%). In the unadjusted analyses, the rate of NI was 8% in the PPI exposed group versus 2% in the nonexposed group. After propensity score matching (n = 184 per group), we failed to identify an association between PPI exposure and greater odds of NI (adjusted odds ratio 2.9 [95% CI, 0.9–9.3]; p = 0.082). However, these data have not excluded the possibility that there is up to nine-fold greater odds of NI.

CONCLUSIONS:

This study highlights the prevalent use of PPIs in the PICU, and the potential association between PPIs and nine-fold greater odds of NI is not excluded.
Business of Medicine in the Academic Plastic Surgery Community
Authors: Khetpal Sumun , Hauc Sacha , Lopez Joseph , Prsic Adnan
Published: August 2022

Purpose

Business fundamentals, such as leadership, negotiations, and personal finance, remain as an overlooked component of residency education. It remains unclear how faculty members in academic plastic surgery particularly view the integration of a business curriculum within plastic surgery residency curriculum and how one's personal exposure to business concepts may impact their perception on the importance of learning such concepts in surgical training.

Methods

A 15-question survey was distributed through the American College of Academic Plastic Surgeons members in order to assess how academic plastic surgeons perceived the importance of a business curriculum and, if applicable, how the formalized study of these concepts were incorporated within plastic surgery residency programs. Surgeons were also queried about barriers toward organizing and executing such a curriculum and about the importance of certain topics for education.

Results

Fifty-five academic plastic surgeons, representing 25 institutions, completed the survey. More than 60% of academic plastic surgeons either strongly agreed or agreed to a formalized business curriculum being a necessary component of residency curriculum, and more than 70% either strongly agreed or agreed to wishing for more instruction in such concepts.

Conclusion

This study elucidates how academic plastic surgeons perceive the education of business fundamentals during plastic surgery training. Although the majority of respondents found such teachings as valuable, our findings suggest limited resources allocated to these important concepts. Future efforts should incentivize plastic surgery programs to provide formal instruction within the business of medicine and, in doing so, position trainees for success in their careers.
Nanobdella aerobiophila gen. nov., sp. nov., a thermoacidophilic, obligate ectosymbiotic archaeon, and proposal of Nanobdellaceae fam. nov., Nanobdellales ord. nov. and Nanobdellia class. nov.
Authors: Kato Shingo , Ogasawara Ayaka , Itoh Takashi , Sakai Hiroyuki D. , Shimizu Michiru , Yuki Masahiro , Kaneko Masanori , Takashina Tomonori , Ohkuma Moriya
Published: August 2022

A co-culture of a novel thermoacidophilic, obligate symbiotic archaeon, designated as strain MJ1T, with its specific host archaeon

Metallosphaera sedula

strain MJ1HA was obtained from a terrestrial hot spring in Japan. Strain MJ1T grew in the co-culture under aerobic conditions. Coccoid cells of strain MJ1T were 200–500 nm in diameter, and attached to the MJ1HA cells in the co-culture. The ranges and optima of the growth temperature and pH of strain MJ1T in the co-culture were 60–75 °C (optimum, 65–70 °C) and pH 1.0–4.0 (optimum, pH 2.5), respectively. Core lipids of dialkyl glycerol tetraethers (GDGT)−3 and GDGT-4 were highly abundant in MJ1T cells concentrated from the co-culture. Strain MJ1T has a small genome (0.67 Mbp) lacking genes for biosynthesis of essential biomolecules, such as nucleotides, lipids and ATP. The genomic DNA G+C content was 24.9 mol%. The 16S rRNA gene sequence of strain MJ1T was most closely related to that of the cultivated species, ‘Nanopusillus acidilobi’ strain N7A (85.8 % similarity). Based on phylogenetic and physiological characteristics, we propose the name Nanobdella aerobiophila gen. nov., sp. nov. to accommodate the strain MJ1T (=JCM 33616T=DSM 111728T). In addition, we propose the names Nanobdellaceae fam. nov., Nanobdellales ord. nov., and Nanobdellia class. nov. to accommodate the novel genus.
Evaluation of RT-PCR pooling test for the detection of SARS-CoV-2 in low-resource setting
Authors: Maharjan Narayani , Thapa Niresh , Magar Bibek Pun , Maharjan Muna , Tu Jiancheng
Published: August 2022

Background

Specimen pooling is an efficient method when there is limited accessibility or scarcity of test kits and reagents for nucleic acid extraction and molecular detection. We evaluated the ability of the standard real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test for detecting a single positive sample of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within a pool of negative samples and to find out the maximum pool dilution limit up to which a single positive sample can be detected.

Methods

RNA extracts from nasopharyngeal and oropharyngeal samples were pooled for the detection of the SARS-CoV-2 virus by RT-PCR. Positive samples were serially diluted in negative samples pools with dilutions ranging from 1/2 to 1/64 to estimate the optimal pool size. The viral transport medium (VTM) of three positive samples was also evaluated for optimal pool size determination.

Results

A single positive sample with a Cycle threshold (Ct) value range from 16-23 (high viral load) can be detected in dilution pools upto1/64 for both genes. In pooling before RNA extraction, a positive sample with a low Ct value (13) and intermediate Ct value (25) was detected till 1/32 dilution pool but a positive sample with a high Ct value (32) was not detected further 1/4 dilution. Besides, two positive VTM samples were detected in pools of sizes 5, 8, and 10.

Conclusions

This study concluded that sample testing by pooling is reliable if done properly and can help increase testing capacity in a low-resource setting.
Seasonal variations in social contact patterns in a rural population in north India: Implications for pandemic control
Authors: Nagpal Sargun , Kumar Rakesh , Noronha Riz Fernando , Kumar Supriya , Gupta Debayan , Amarchand Ritvik , Gosain Mudita , Sharma Hanspria , Menon Gautam I. , Krishnan Anand
Published: August 2022

Social contact mixing patterns are critical to the transmission of communicable diseases and have been employed to model disease outbreaks including COVID-19. Nonetheless, there is a paucity of studies on contact mixing in low and middle-income countries such as India. Furthermore, mathematical models of disease outbreaks do not account for the temporal nature of social contacts. We conducted a longitudinal study of social contacts in rural north India across three seasons and analysed the temporal differences in contact patterns.

A contact diary survey was performed across three seasons from October 2015-16, in which participants were queried on the number, duration, and characteristics of contacts that occurred on the previous day. A total of 8,421 responses from 3,052 respondents (49% females) recorded characteristics of 180,073 contacts. Respondents reported a significantly higher number and duration of contacts in the winter, followed by the summer and the monsoon season (Nemenyi post-hoc, p<0.001). Participants aged 0-9 years and 10-19 years of age reported the highest median number of contacts (16 (IQR 12-21), 17 (IQR 13-24) respectively) and were found to have the highest node centrality in the social network of the region (pageranks = 0.20, 0.17). Employed males across all age groups were found to have a higher number of contacts than unemployed males (Negative Binomial Regression: rate ratio 1.18, 95% CI: 1.05-1.31). A large proportion (>80%) of contacts that were reported in schools or on public transport involved physical contact.

To the best of our knowledge, our study is the first from India to show that contact mixing patterns vary by the time of the year and provides useful implications for pandemic control. Our results can be used to parameterize more accurate mathematical models for prediction of epidemiological trends of infections in rural India.
Symptom presentation among SARS-CoV-2 positive cases and the impact of COVID-19 vaccination; three prospective household cohorts
Authors: Westerhof Ilse , de Hoog Marieke , Ieven Margareta , Lammens Christine , van Beek Janko , Rozhnova Ganna , Eggink Dirk , Euser Sjoerd , Wildenbeest Joanne , Duijts Liesbeth , van Houten Marlies , Goossens Herman , Giaquinto Carlo , Bruijning-Verhagen Patricia
Published: August 2022

OBJECTIVE

Using data from European prospective household studies, we systematically compared the symptom burden of the wild-type and Alpha variant infected individuals versus the Omicron BA.1 and BA.2 infected individuals across paediatric and adult age-groups. In addition, we measured the impact of COVID-19 vaccination on the Omicron symptom burden.

METHODS

The household transmission studies were conducted during the wild-type and Alpha period (April 2020 to April 2021) and the early Omicron BA.1 and BA.2 dominant period (January to March 2022). All three studies used similar protocols. Households were prospectively followed from detection of the first SARS-CoV-2 index case until at least day 21 including (repeated) PCR testing, paired serology and daily symptom reporting for all household members. To avoid possible index-case ascertainment bias, we restricted analyses to secondary household cases. Age-stratified SARS-CoV-2 symptom burden was compared for wild-type/Alpha versus Omicron infections and for primary versus primary plus booster series vaccinated adult cases.

FINDINGS

In total 216 secondary cases from wild-type/Alpha, and 130 from the Omicron period were included. Unvaccinated children <12 years experienced more symptoms and higher maximum and cumulative severity scores during the Omicron compared to the wild-type/Alpha period (p=0.004, p=0.011 and p=0.075, respectively). In adults, disease duration and maximum and cumulative severity scores were reduced during the Omicron period. Adjusted for age, gender and prior immunity Omicron was associated with lower odds for loss of smell or taste (Odds Ratio [OR]: 0.14; 95%CI 0.03-0.50), and higher, but non-significant odds for upper respiratory symptoms, fever and fatigue (ORs varying between 1.85-2.23). Comparing primary versus primary plus booster vaccinated adult cases during the Omicron period no differences were observed in disease severity or duration (p≥0.12).

INTERPRETATION

In children, the Omicron variant causes higher symptom burden compared to the wild-type/Alpha. Adults experienced a lower symptom burden possibly due to prior vaccination. A shift in most frequently reported symptoms occurred with a marked reduction in loss of smell or taste during the Omicron period. An additional effect of booster vaccination on symptom severity in infected adults compared to primary series only, could not be demonstrated.
Differentiation of human induced pluripotent stem cells into cortical neural stem cells
Authors: Neaverson Alexandra , Andersson Malin H. L. , Arshad Osama A. , Foulser Luke , Goodwin-Trotman Mary , Hunter Adam , Newman Ben , Patel Minal , Roth Charlotte , Thwaites Tristan , Kilpinen Helena , Hurles Matthew E. , Day Andrew , Gerety Sebastian S.
Published: August 2022

Efficient and effective methods for converting human induced pluripotent stem cells (iPSC) into differentiated derivatives are critical for performing robust, large-scale studies of development and disease modelling, and for providing a source of cells for regenerative medicine. Here, we describe a 14-day neural differentiation protocol which allows for the scalable, simultaneous differentiation of multiple iPSC lines into cortical neural stem cells (NSCs). We currently employ this protocol to differentiate and compare sets of engineered iPSC lines carrying loss of function alleles in developmental disorder associated genes, alongside isogenic wildtype controls. Using RNA sequencing (RNA-Seq), we can examine the changes in gene expression brought about by each disease gene knockout, to determine its impact on neural development and explore mechanisms of disease. The 10-day Neural Induction period uses the well established dual-SMAD inhibition approach combined with Wnt/β-Catenin inhibition to selectively induce formation of cortical NSCs. This is followed by a 4-day Neural Maintenance period facilitating NSC expansion and rosette formation, and NSC cryopreservation. We also describe methods for thawing and passaging the cryopreserved NSCs, which are useful in confirming their viability for further culture. Routine implementation of ICC Quality Control confirms the presence of PAX6-positive and/or FOXG1-positive NSCs and the absence of OCT4-positive iPSCs after differentiation. RNA-Seq, flow cytometry, immunocytochemistry (ICC) and RT-qPCR provide additional confirmation of robust presence of NSC markers in the differentiated cells. The broader utility and application of our protocol is demonstrated by the successful differentiation of wildtype iPSC lines from five additional independent donors. This paper thereby describes an efficient method for the production of large numbers of high purity cortical NSCs, which are widely applicable for downstream research into developmental mechanisms, further differentiation into postmitotic cortical neurons, or other applications such as large-scale drug screening experiments.
Prosocial behavior, social reward and affective state discrimination in adult male and female mice
Authors: Misiołek Klaudia , Klimczak Marta , Chrószcz Magdalena , Szumiec Łukasz , Bryksa Anna , Przyborowicz Karolina , Rodriguez Parkitna Jan , Harda Zofia
Published: August 2022

Prosocial behavior, defined as voluntary behavior intended to benefit another, has long been regarded as a primarily human characteristic. In recent years, it was reported that laboratory animals also favor prosocial choices in various experimental paradigms, thus demonstrating that prosocial behaviors are evolutionarily conserved. Here, we investigated prosocial choices in adult male and female C57BL/6 laboratory mice in a task where a subject mouse is equally rewarded for entering any of the two compartments of the experimental cage, but only entering of the compartment designated as “prosocial” rewards an interaction partner. In parallel we have also assessed two traits that are regarded as closely related to prosociality: sensitivity to social reward and the ability to recognize the affective state of another individual. We find that female, but not male, mice increased frequency of prosocial choices from pretest to test. At the same time, both sexes showed similar rewarding effects of social contact in the conditioned place preference test, and similarly, there was no effect of sex on affective state discrimination measured as the preference for interaction with a hungry or relieved mouse over a neutral animal. These observations bring interesting parallels to differences between sexes observed in humans, and are in line with reported higher propensity for prosocial behavior in human females, but differ with regard to sensitivity to social stimuli in males.
Magnetogenetic closed-loop reduction of seizure activity in a rat model of epilepsy
Authors: Metto Abigael C. , Gilad Assaf A. , Pelled Galit
Published: August 2022

On-demand neurostimulation has shown success in epilepsy patients with pharmacoresistant seizures. Seizures produce magnetic fields that can be recorded using magnetoencephalography. We developed a new closed-loop approach to control seizure activity based on magnetogenetics using the electromagnetic perceptive gene (EPG) that encodes a protein that responds to magnetic fields. The EPG transgene was expressed in inhibitory interneurons under hDlx promoter and kainic acid was used to induce acute seizures. In vivo electrophysiological signals were recorded. We found that hDlx EPG rats exhibited a significant delay in the onset of first seizure (1142.72 ± 186.35s) compared to controls (644.03 ± 15.06s) and significantly less seizures (4.11 ± 1.03) compared to controls (8.33 ± 1.58). These preliminary findings suggest that on-demand activation of EPG expressed in inhibitory interneurons suppress seizure activity, and magnetogenetics via EPG may be an effective strategy to alleviate seizure severity in a minimally invasive, closed-loop and cell-specific fashion.
Noisy neuronal populations effectively encode sound localization in the dorsal inferior colliculus of awake mice
Authors: Boffi Juan C. , Bathellier Brice , Asari Hiroki , Prevedel Robert
Published: August 2022

Sound location coding has been extensively studied at the central nucleus of the mammalian inferior colliculus (CNIC), supporting a population code. However, this population code has not been extensively characterized on the single-trial level with simultaneous recordings or at other anatomical regions like the dorsal cortex of inferior colliculus (DCIC), which is relevant for learning-induced experience dependent plasticity. To address these knowledge gaps, here we made in two complementary ways large-scale recordings of DCIC populations from awake mice in response to sounds delivered from 13 different frontal horizontal locations (azimuths): volumetric two-photon calcium imaging with ∼700 cells simultaneously recorded at a relatively low temporal resolution, and high-density single-unit extracellular recordings with ∼20 cells simultaneously recorded at a high temporal resolution. Independent of the method, the recorded DCIC population responses revealed substantial trial-to-trial variation (neuronal noise) which was significantly correlated across pairs of neurons (noise correlations) in the passively listening condition. Nevertheless, decoding analysis supported that these noisy response patterns encode sound location on the single-trial basis, reaching errors that match the discrimination ability of mice. The detected noise correlations contributed to minimize the error of the DCIC population code of sound azimuth. Altogether these findings point out that DCIC can encode sound location in a similar format to what has been proposed for CNIC, opening exciting questions about how noise correlations could shape this code in the context of cortico-collicular input and experience dependent plasticity.
α-Synuclein pathology and reduced neurogenesis in the olfactory system affect olfaction in a mouse model of Parkinson’s disease
Authors: Martin-Lopez Eduardo , Vidyadhara D.J. , Liberia Teresa , Meller Sarah J. , Harmon Leah E. , Hsu Ryan M. , Han Kimberly , Yücel Betül , Chandra Sreeganga S. , Greer Charles A.
Published: August 2022

Parkinson’s Disease (PD) is characterized by multiple symptoms including olfactory dysfunction, whose underlying mechanisms remain unclear. Here, we explored pathological changes in the olfactory pathway of transgenic (Tg) mice expressing the human A30P mutant α-synuclein (α-syn) (α-syn-Tg mice) at 6-7 and 12-14 months of age, representing early and late-stages of motor progression, respectively. α-Syn-Tg mice at late stages exhibited olfactory behavioral deficits, which correlated with severe α-syn pathology in projection neurons of the olfactory pathway. In parallel, olfactory bulb (OB) neurogenesis in α-syn-Tg mice was reduced in the OB granule cells at 6-7 months, and OB periglomerular cells at 12-14 months, respectively, both of which could contribute to olfactory dysfunction. Proteomic analyses showed a disruption in endo- and exocytic pathways in the OB during the early stages which appeared exacerbated at the synaptic terminals when the mice developed olfactory deficits at 12-14 months. Our data suggest that, 1) the α-syn-Tg mice recapitulate the olfactory functional deficits seen in PD; 2) olfactory structures exhibit spatiotemporal disparities for vulnerability to α-syn pathology; 3) α-syn pathology is restricted to projection neurons in the olfactory pathway; 4) neurogenesis in adult α-syn-Tg mice is reduced in the OB; and 5) synaptic endo- and exocytosis defects in the OB may further explain olfactory deficits.
Geometric differences in the ribosome exit tunnel impact the escape of small nascent proteins
Authors: Yu Shiqi , Srebnik Simcha , Duc Khanh Dao
Published: August 2022

The exit tunnel is the sub-compartment of the ribosome that contains the nascent polypeptide chain and as such, is involved in various vital functions, including regulation of translation and protein folding. As the geometry of the tunnel shows important differences across species, we focus on key geometrical features of eukaryote and prokaryote tunnels. We used a simple coarse-grained molecular dynamics model to study the role of the tunnel geometry in the post-translational escape of short proteins (sORF’s), with lengths ranging from 6 to 56 amino acids. We found that the probability of escape for prokaryotes is one for all but the 12-mer chains. Moreover, proteins of this length have an extremely low escape probability in eukaryotes. A detailed examination of the associated single trajectories and energy profiles showed that these variations can be explained by the interplay between the protein configurational space and the confinement effects introduced by the constriction sites of the ribosome exit tunnel. For certain lengths, either one or both of the constriction sites can lead to the trapping of the protein in the “pocket” regions preceding these sites. As the distribution of existing sORF’s indicate some bias in length that is consistent with our findings, we finally suggest that the constraints imposed by the tunnel geometry have impacted the evolution of sORF’s.
Increasing the efficacy of exposure using a whole brain approach to real-time fMRI neurofeedback among female victims of interpersonal violence
Authors: Calvert Maegan L. , Cisler Josh M. , Bush Keith A.
Published: August 2022

Individuals who experience interpersonal violence (IPV) and poly-victimization have an increased likelihood of developing Posttraumatic Stress Disorder (PTSD), and statistically, women are more likely than men to be victims of IPV, experience poly-victimization, and develop PTSD. Current gold-standard PTSD treatments utilize exposure, a key mechanism of change; however, exposure-based treatments suffer from moderate remission rates. This outcome underscores the importance of utilizing knowledge of neural mechanisms to increase treatment effectiveness and PTSD remission rates. The current study used a symptom provocation paradigm, which is conceptually similar to exposure, and whole brain multivariate pattern classifiers (MVPC) to provide participants with neurofeedback on their ability to regulate their brain-states. In the MRI scanner, women (N = 21; control n = 11, PTSD n = 10) completed a symptom provocation paradigm. The MVPC was constructed during the first two runs and neurofeedback was given during the third and fourth run. During all four runs, participants were instructed to increase or decrease their emotional engagement with their stress/trauma script and during the last two runs, participants were provided visual feedback indicating their performance in regulating brain states. Skin conductance response was utilized as an independent measure of physiological arousal. Generalized linear models indicated a significant interaction effect of feedback and condition as well as feedback and group. Generalized linear models of skin conductance response largely mirrored these findings. Results indicate neurofeedback of whole brain activation can be utilized to increase engagement with trauma memories. Thus, exposure-based treatments, possibly with refractory cases of PTSD, may be improved with neurofeedback by providing the therapist and patient insight into their brain-state during exposure which may increase the effectiveness of exposure-based treatments.
LONGITUDINAL CLUSTER ANALYSIS OF HEMODIALYSIS PATIENTS WITH COVID-19 IN THE PRE-VACCINATION ERA
Authors: Esposito Pasquale , Garbarino Sara , Fenoglio Daniela , Cama Isabella , Cipriani Leda , Campi Cristina , Parodi Alessia , Vigo Tiziana , Franciotta Diego , Altosole Tiziana , Grosjean Fabrizio , Viazzi Francesca , Filaci Gilberto , Piana Michele
Published: August 2022

Coronavirus disease 2019 (COVID-19) is characterized by a high heterogeneity of clinical presentation and outcomes. This is also true for patients undergoing maintenance hemodialysis (HD), who, due to specific clinical factors and immune status, represent a distinct subgroup of COVID-19 patients.

Starting from this observation in this research letter we tested and validated in two cohorts of HD patients with COVID-19 (derivation and validation cohort, respectively) an innovative model which combines linear mixed effect modeling and cluster analysis on longitudinal.

This study aimed to describe a methodology allowing patient stratification from simple and widely available data.

Our results could be interesting not only to improve COVID-19 management but also to support the application of longitudinal cluster analysis strategy in other clinical settings.
Acquiring thin histological sections of açaí (Euterpe oleracea Mart.) seeds for molecular mapping by mass spectrometry imaging
Authors: Brum Felipe Lopes , Martins Gabriel Rocha , Mohana-Borges Ronaldo , da Silva Ayla Sant’Ana
Published: August 2022

RATIONALE

Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) of tissues became popular in the last decade. Consequently, adapting sample preparation methods for different materials turned to be a pivotal step for a successful analysis, due to the requirement of samples slices of 12-20 μm thickness. However, preparing thin sections compatible with MALDI-IMS for unusual samples is challenging, as existing histological protocols may not be suitable, thus requiring new methods. Açaí (Euterpe oleracea Mart.) seed is an example of a challenging material due to its toughness and resistance to crack. Therefore, our goal was to develop a methodology to obtain thin (<20 μm) and entire longitudinal sections of açaí seeds for MALDI-IMS analysis.

METHODS

Different strategies were evaluated for obtaining thin cuts of seeds, being the combination of the following steps the most suitable option: (i) softening of seeds by water immersion for 24 h; (ii) longitudinal cut of seeds to obtain half-seeds using a razor blade and a hammer; (iii) half-seeds imbibition in gelatin; (iv) sectioning using a cryostat at −20 °C to obtain samples with <20 μm thickness; and (v) collection of samples in an indium tin oxide coated glass slide covered by a double-face copper tape to avoid sample wrapping and ensure adhesion after unfreezing. (iv) storage of samples in a −80 °C freezer, if necessary.

RESULTS

As a result, this adapted sample preparation method enabled the analysis of açaí seeds by MALDI-IMS providing spatial distribution of carbohydrates in the endosperm.

CONCLUSIONS

The adaptations developed for sample preparation will help investigate the metabolic and physiological properties of açaí seeds in future studies.
Rodent Automated Bold Improvement of EPI Sequences (RABIES): A standardized image processing and data quality platform for rodent fMRI
Authors: Desrosiers-Gregoire Gabriel , Devenyi Gabriel A. , Grandjean Joanes , Chakravarty M. Mallar
Published: August 2022

Functional magnetic resonance imaging (fMRI) in rodents holds great potential for advancing our understanding of brain networks. Unlike the human fMRI community, there remains no standardized resource in rodents for image processing, analysis and quality control, posing significant reproducibility limitations. Our software platform, Rodent Automated Bold Improvement of EPI Sequences (RABIES), is a novel pipeline designed to address these limitations for preprocessing, quality control, and confound correction, along with best practices for reproducibility and transparency. We demonstrate the robustness of the preprocessing workflow by validating performance across multiple acquisition sites and both mouse and rat data. Building upon a thorough investigation into data quality metrics across acquisition sites, we introduce guidelines for the quality control of network analysis and offer recommendations for addressing issues. Taken together, the RABIES software will allow the emerging community to adopt reproducible practices and foster progress in translational neuroscience.
Development of Metal organic Framework Based Biosensor to Detect the Coronavirus (Covid-19)
Authors: Alkhodairy Hanoof Fahad , Naeem Muhammad , Helal Aasif , Khalil Amjad Bajis
Published: August 2022

Recent outbreak of novel coronavirus (COVID-19) caused around 7 million deaths people worldwide and still afflicting on the global health, economy and social setup. Timely detection and diagnosis are crucial steps to reduce the spread and prevention of any pandemic. Different types of diagnosis methos has been used. In last decade nanomaterials and metal organic frameworks (MOFs) based biosensors has been developed to detect the other viruses. We have designed the Zeolitic imidazolate framework-8 (ZIF-8) based biosensor to detect the COVID-19. ZIF-8 work as fluorescence quenching and re-emergence platform to detect the COVID-19 RNA sequences. ZIF-8 platform is highly sensitive which can distinguish the highly conserved single strand RNA and with 200 pM concentrations. It can distinguish down to the single mismatch nucleotide in RNA sequences.