bluuebunny/crossref_metadata_2025 huggingface dataset:
Posterior versus lateral surgical approach: functionality and quality of life after total hip arthroplasty in a matched cohort study
Authors: Castioni Davide , Galasso Olimpio , Iannò Bruno , Mercurio Michele , Gasparini Giorgio
Published: November 2021

Background

One of the most controversial aspects for maximizing outcomes after total hip arthroplasty (THA) remains the surgical approach to the hip joint. The posterior (PA) and lateral approaches (LA) are the two most commonly performed approaches used worldwide, but sparse data are available for their comparison in terms of health-related quality-of-life (HRQoL). The aim of this study was to assess the role of the PA and LA in the HRQoL and hip functionality of patients who underwent primary and elective THA for osteoarthritis, after a minimum 2-year follow-up.

Methods

One hundred twenty-eight patients (140 THAs: 68 with PA and 72 with LA) were evaluated in a matched cohort study. Data gathered included the body mass index, the American Society of Anesthesiologists score, surgery time, serum creatine phosphokinase (CpK) levels, estimated intraoperative blood loss and intra- or postoperative complications. Preoperatively and at the last follow-up, the activities of daily living, and the instrumental activities of daily living (IADL) scales, the Western Ontario and Mac Master University (WOMAC) Questionnaire, the Harris Hip Score (HHS) and the Visual Analogue Scale (VAS) were used to assess HRQoL and functionality. The Short Form-36 Health Survey (SF-36) Questionnaire was administered at the last follow-up.

Results

Postoperatively, CpK was higher in the LA group compared to the PA (695 ± 648 vs. 447 ± 326 UI/L, p < 0.001). At a mean follow-up of 47 ± 22 months for the LA group and 42 ± 29 months for the PA group, IADL, VAS, HHS and WOMAC scores significantly improved for both groups (all p < 0.001), but PA reported better VAS, residual pain and WOMAC scores (p = 0.002, p = 0.004 and p = 0.018, respectively). The PA group demonstrated a significant higher mental SF-36 subscale values than the LA group (49 ± 13 vs. 42 ± 19, p = 0.001). The LA group showed a higher number of Trendelenburg signs (p = 0.029). On the contrary, the PA group showed a higher number of leg lengthening (p = 0.020); however, most of these cases was less than the clinically significant value of 10 mm (p = 0.738).

Conclusions

Patients who underwent THA performed with the PA reported greater improvement in HRQoL with lower residual pain, postoperative muscle damage and Trendelenburg signs than those who underwent the LA.
Dental follicles promote soft tissue management in surgical exposure of labially impacted maxillary canine
Authors: Hu Li-Ru , Qi Wen-Ting , Bao Chong-Yun , Pan Jian , Liu Xian
Published: November 2021

Background

The present study aimed to report a technically improved operation on the surgical exposure of labially impacted maxillary canine, elaborating the management of soft tissue to achieve better aesthetic results, and post-treatment periodontal health.

Methods

Patients sought orthodontic treatment with unilateral labially impacted maxillary canines were selected in this study. The impacted teeth were assigned to the experimental group and contralateral unimpacted canines were assigned to the control group. The impacted canines were surgically exposed with dissected dental follicle (DF) stitching to muscle and mucosa surrounding the crowns. The gingival index (GI), probing depth (PD), the width of the keratinized gingiva (WKG), gingival scars (GS), bone loss (BL), and apical root resorption (ARR) were recorded after the removal of the fixed appliance. A two-sample t-test was used for independent samples for parametric variables.

Results

A total of 24 patients with unilateral maxillary canine impaction were successfully treated. The outcomes of GI, WKG, GS, BL, and ARR did not indicate statistical significance between the experimental group and the control group.

Conclusions

The preservation of DF promotes soft tissue management in combined surgical and orthodontic treatment of labially impacted maxillary canine to achieve better periodontal status.

Trial Registration Chinese Clinical Trial Registry ChiCTR2000029091, 2020-01-12.
Healthcare avoidance: a qualitative study of dental care avoidance in Germany in terms of emergent behaviours and characteristics
Authors: Gragoll Isabell , Schumann Lukas , Neubauer Monique , Westphal Christina , Lang Hermann
Published: November 2021

Background

The treatment of acute pain is part of everyday dental practice. Often, these symptoms result from years of patients' inadequate or missing dental routines and lead to a reduction in the quality of life or health of the patients and to high costs for the health care system. Despite the enormous advantages of modern dentistry, many patients avoid going to the dentist. Therefore, the study aimed to determine the reasons and behaviours that cause patients to avoid visits to the dentist.

Methods

We conducted semi-structured interviews with patients who had an above-average DMFT index and had been going to the dentist only irregularly for years. The sample participants were recruited from the northern German region of Mecklenburg-Western Pomerania. 20 individual interviews were recorded, transcribed verbatim and coded. We used a qualitative framework approach to code the transcripts in order to establish a consensus among the researchers. Ultimately, through discussions and reviews of the attributes and meaning of the topics, a typology could be established.

Results

A typology of patients who avoid the dentist was developed. Four independent characteristic patterns of dentist avoidance could be developed: avoiding the dentist due to "distance" (type A; includes subtype A1 "avoiding the dentist due to negligence" and subtype A2 "dental avoidance due to neutralization"), "disappointment" (type B), "shame" (type C), and "fear" (type D). Using the typology as a generalised tool to determine the minimum and maximum contrasts, it was possible to capture the diversity and multidimensionality of the reasons and behaviours for avoidance. All patients had negative dental experiences, which had led to different avoidance patterns and strategies.

Conclusions

The identified avoidance characteristics represent a spectrum of patients from Northern Germany who avoid going to the dentist. This is the first comprehensive study in Germany representing avoidance behaviour of dentist patients in the form of a typology. The results suggest that dentistry also needs qualitative research to better understand patient characteristics and provide direct access to patients who avoid regular dental visits. Thus, the results make a potentially fundamental contribution to the improvement of dental care and enrich its understanding.
Number of teeth is associated with all-cause and disease-specific mortality
Authors: Yu Yau-Hua , Cheung Wai S. , Steffensen Bjorn , Miller Donald R.
Published: November 2021

Background

Tooth loss has been shown to correlate with multiple systemic comorbidities. However, the associations between the number of remaining natural teeth (NoT) and all-cause mortality have not been explored extensively. We aimed to investigate whether having fewer NoT imposes a higher risk in mortality. We tested such hypotheses using three groups of NoT (20–28,10–19, and 0–9), edentulism and without functional dentition (NoT < 19).

Methods

The National Health and Nutrition Examination Survey in the United States (NHANES) (1999–2014) conducted dental examinations and provided linkage of mortality data. NHANES participants aged 20 years and older, without missing information of dental examination, age, gender, race, education, income, body-mass-index, smoking, physical activities, and existing systemic conditions [hypertension, total cardiovascular disease, diabetes, and stroke (N = 33,071; death = 3978), or with femoral neck bone mineral density measurement (N = 13,131; death = 1091)] were analyzed. Cox proportional hazard survival analyses were used to investigate risks of all-cause, heart disease, diabetes and cancer mortality associated with NoT in 3 groups, edentulism, or without functional dentition.

Results

Participants having fewer number of teeth had higher all-cause and disease-specific mortality. In fully-adjusted models, participants with NoT0-9 had the highest hazard ratio (HR) for all-cause mortality [HR(95%CI) = 1.46(1.25–1.71); p < .001], mortality from heart diseases [HR(95%CI) = 1.92(1.33–2.77); p < .001], from diabetes [HR(95%CI) = 1.67(1.05–2.66); p = 0.03], or cancer-related mortality [HR(95%CI) = 1.80(1.34–2.43); p < .001]. Risks for all-cause mortality were also higher among the edentulous [HR(95%CI) = 1.35(1.17–1.57); p < .001] or those without functional dentition [HR(95%CI) = 1.34(1.17–1.55); p < .001].

Conclusions

Having fewer NoT were associated with higher risks for all-cause mortality. More research is needed to explore possible biological implications and validate our findings.
‘As long as I have a restroom somewhere […], I am fine’: a qualitative study on the perspectives of peri- and postmenopausal women on the impact of the urinary component of the genitourinary syndrome of menopause (GSM)
Authors: Gabes Michaela , Kann Gesina , von Sommoggy Julia , Stute Petra , Apfelbacher Christian J.
Published: November 2021

Background

Our aim was to gain insight into the experiences of women suffering from the urinary component of the Genitourinary Syndrome of Menopause (GSM) and to understand the impact of urinary complaints as part of GSM on the lives of affected women.

Design

Qualitative study.

Setting

Online, primary care.

Participants and methods

Postmenopausal women aged from 46 to 85 years reporting vaginal and urinary complaints were recruited to participate in either online or face-to-face focus groups to share their experiences with urinary complaints as part of GSM. Transcripts of sessions were analysed using qualitative content analysis.

Results

One online focus group, one face-to-face focus group and one online-interview were conducted, involving 11 women. Five a priori assumed main themes related to the impact of urogenital symptoms were identified: daily life, emotional well-being, sexual functioning, self-concept and body image, and interpersonal relations and communication. Additionally, two further themes associated with GMS as a clinical condition were inductively found: unmet healthcare needs, including expectations of affected women regarding menopausal symptoms and a lack of adequate health education, and aspects on the personal dealing with the complaints, including personal coping strategies and medical treatment.

Conclusions

This study showed that urinary complaints as part of GSM have, similar to vaginal complaints, negative impacts on the daily life, the emotional well-being, the sexual functioning, the self-concept and body impact as well as interpersonal relations and communication of affected women. We further identified several unmet healthcare needs that should trigger improvements in healthcare.
Establishing an expert consensus for the operational definitions of asthma-associated infectious and inflammatory multimorbidities for computational algorithms through a modified Delphi technique
Authors: Yoon Jungwon , Billings Heather , Wi Chung-Il , Hall Elissa , Sohn Sunghwan , Kwon Jung Hyun , Ryu Euijung , Shrestha Pragya , Liu Hongfang , Juhn Young J.
Published: November 2021

Background

A subgroup of patients with asthma has been reported to have an increased risk for asthma-associated infectious and inflammatory multimorbidities (AIMs). To systematically investigate the association of asthma with AIMs using a large patient cohort, it is desired to leverage a broad range of electronic health record (EHR) data sources to automatically identify AIMs accurately and efficiently.

Methods

We established an expert consensus for an operational definition for each AIM from EHR through a modified Delphi technique. A series of questions about the operational definition of 19 AIMS (11 infectious diseases and 8 inflammatory diseases) was generated by a core team of experts who considered feasibility, balance between sensitivity and specificity, and generalizability. Eight internal and 5 external expert panelists were invited to individually complete a series of online questionnaires and provide judgement and feedback throughout three sequential internal rounds and two external rounds. Panelists’ responses were collected, descriptive statistics tabulated, and results reported back to the entire group. Following each round the core team of experts made iterative edits to the operational definitions until a moderate (≥ 60%) or strong (≥ 80%) level of consensus among the panel was achieved.

Results

Response rates for each Delphi round were 100% in all 5 rounds with the achievement of the following consensus levels: (1) Internal panel consensus: 100% for 8 definitions, 88% for 10 definitions, and 75% for 1 definition, (2) External panel consensus: 100% for 12 definitions and 80% for 7 definitions.

Conclusions

The final operational definitions of AIMs established through a modified Delphi technique can serve as a foundation for developing computational algorithms to automatically identify AIMs from EHRs to enable large scale research studies on patient’s multimorbidities associated with asthma.
Polygenic risk score across distinct colorectal cancer screening outcomes: from premalignant polyps to colorectal cancer
Authors: Obón-Santacana Mireia , Díez-Villanueva Anna , Alonso Maria Henar , Ibáñez-Sanz Gemma , Guinó Elisabet , López Ana , Rodríguez-Alonso Lorena , Mata Alfredo , García-Rodríguez Ana , Palomo Andrés García , Molina Antonio J. , Garcia Montse , Binefa Gemma , Martín Vicente , Moreno Victor
Published: November 2021

Background

Different risk-based colorectal cancer (CRC) screening strategies, such as the use of polygenic risk scores (PRS), have been evaluated to improve effectiveness of these programs. However, few studies have previously assessed its usefulness in a fecal immunochemical test (FIT)-based screening study.

Methods

A PRS of 133 single nucleotide polymorphisms was assessed for 3619 participants: population controls, screening controls, low-risk lesions (LRL), intermediate-risk (IRL), high-risk (HRL), CRC screening program cases, and clinically diagnosed CRC cases. The PRS was compared between the subset of cases (n = 648; IRL+HRL+CRC) and controls (n = 956; controls+LRL) recruited within a FIT-based screening program. Positive predictive values (PPV), negative predictive values (NPV), and the area under the receiver operating characteristic curve (aROC) were estimated using cross-validation.

Results

The overall PRS range was 110–156. PRS values increased along the CRC tumorigenesis pathway (Mann-Kendall P value 0.007). Within the screening subset, the PRS ranged 110-151 and was associated with higher risk-lesions and CRC risk (ORD10vsD1 1.92, 95% CI 1.22–3.03). The cross-validated aROC of the PRS for cases and controls was 0.56 (95% CI 0.53–0.59). Discrimination was equal when restricted to positive FIT (aROC 0.56), but lower among negative FIT (aROC 0.55). The overall PPV among positive FIT was 0.48. PPV were dependent on the number of risk alleles for positive FIT (PPVp10-p90 0.48–0.57).

Conclusions

PRS plays an important role along the CRC tumorigenesis pathway; however, in practice, its utility to stratify the general population or as a second test after a FIT positive result is still doubtful. Currently, PRS is not able to safely stratify the general population since the improvement on PPV values is scarce.
SToRytelling to Improve Disease outcomes in Gout (STRIDE-GO): a multicenter, randomized controlled trial in African American veterans with gout
Authors: Singh Jasvinder A. , Joseph Amy , Baker Joshua , Richman Joshua S. , Shaneyfelt Terrence , Saag Kenneth G. , Eisen Seth
Published: November 2021

Background

Urate-lowering therapy (ULT) adherence is low in gout, and few, if any, effective, low-cost, interventions are available. Our objective was to assess if a culturally appropriate gout-storytelling intervention is superior to an attention control for improving gout outcomes in African-Americans (AAs).

Methods

In a 1-year, multicenter, randomized controlled trial, AA veterans with gout were randomized to gout-storytelling intervention vs. a stress reduction video (attention control group; 1:1 ratio). The primary outcome was ULT adherence measured with MEMSCap™, an electronic monitoring system that objectively measured ULT medication adherence.

Results

The 306 male AA veterans with gout who met the eligibility criteria were randomized to the gout-storytelling intervention (n= 152) or stress reduction video (n= 154); 261/306 (85%) completed the 1-year study. The mean age was 64 years, body mass index was 33 kg/m2, and gout disease duration was 3 years. ULT adherence was similar in the intervention vs. control groups: 3 months, 73% versus 70%; 6 months, 69% versus 69%; 9 months, 66% versus 67%; and 12 months, 61% versus 64% (p> 0.05 each). Secondary outcomes (gout flares, serum urate and gout-specific health-related quality of life [HRQOL]) in the intervention versus control groups were similar at all time points except intervention group outcomes were better for the following: (1) number of gout flares at 9 months were fewer, 0.7 versus 1.3 in the previous month (p= 0.03); (2) lower/better scores on two gout specific HRQOL subscales: gout medication side effects at 3 months, 32.8 vs. 39.6 (p= 0.02); and unmet gout treatment need at 3 months, 30.9 vs. 38.2 (p= 0.003), and 6 months, 29.5 vs. 34.5 (p= 0.03), respectively.

Conclusions

A culturally appropriate gout-storytelling intervention was not superior to attention control for improving gout outcomes in AAs with gout.

Trial registration

Registered atClinicalTrials.govNCT02741700
Predicted norovirus resurgence in 2021–2022 due to the relaxation of nonpharmaceutical interventions associated with COVID-19 restrictions in England: a mathematical modeling study
Authors: O’Reilly Kathleen M. , Sandman Frank , Allen David , Jarvis Christopher I. , Gimma Amy , Douglas Amy , Larkin Lesley , Wong Kerry L. M. , Baguelin Marc , Baric Ralph S. , Lindesmith Lisa C. , Goldstein Richard A. , Breuer Judith , Edmunds W. John
Published: November 2021

Background

To reduce the coronavirus disease burden in England, along with many other countries, the government implemented a package of non-pharmaceutical interventions (NPIs) that have also impacted other transmissible infectious diseases such as norovirus. It is unclear what future norovirus disease incidence is likely to look like upon lifting these restrictions.

Methods

Here we use a mathematical model of norovirus fitted to community incidence data in England to project forward expected incidence based on contact surveys that have been collected throughout 2020–2021.

Results

We report that susceptibility to norovirus infection has likely increased between March 2020 and mid-2021. Depending upon assumptions of future contact patterns incidence of norovirus that is similar to pre-pandemic levels or an increase beyond what has been previously reported is likely to occur once restrictions are lifted. Should adult contact patterns return to 80% of pre-pandemic levels, the incidence of norovirus will be similar to previous years. If contact patterns return to pre-pandemic levels, there is a potential for the expected annual incidence to be up to 2-fold larger than in a typical year. The age-specific incidence is similar across all ages.

Conclusions

Continued national surveillance for endemic diseases such as norovirus will be essential after NPIs are lifted to allow healthcare services to adequately prepare for a potential increase in cases and hospital pressures beyond what is typically experienced.
Relationship between genetic polymorphism of drug transporters and the efficacy of Rosuvastatin, atorvastatin and simvastatin in patients with hyperlipidemia
Authors: Sivkov Andrey , Chernus Natalya , Gorenkov Roman , Sivkov Sergey , Sivkova Svetlana , Savina Tamara
Published: November 2021

Background

To determine the effect of genetic polymorphism of drug transporters on the efficacy of treatment with Rosuvastatin, Atorvastatin and Simvastatin in patients with hyperlipidemia.

Methods

The study consists of 180 patients, aged 40–75 years, with hyperlipidemia. All patients were divided into two equal groups: patients with different SLCO1B1 (521CC, 521CT and 521TT) and MDR1 (3435CC, 3435TC and 3435TT) genotypes. Each group was divided into rosuvastatin-treated, atorvastatin-treated and simvastatin-treated subgroups. The lipid-lowering effect of statins was assessed by tracing changes in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels.

Results

The use of statins over a 4-month period led to substantial reductions in TC and LDL-C levels. The hypolipidemic effect of studied agents was seen in both groups. However, it was less pronounced in patients with 521CC genotype. No statistically significantly differences were found between carriers of 3435TT, 3435CT and 3435CC genotypes.

Conclusions

The lipid-lowering efficacy of rosuvastatin was higher compared to other two statins. Patients with SLCO1B1 521CC genotype are more likely to encounter a decrease in the hypolipidemic effect of statins. Such a risk should be considered when treating this category of patients. MDR1 polymorphism had no significant effect on statin efficacy.
The effect of vitamin D, magnesium and zinc supplements on interferon signaling pathways and their relationship to control SARS-CoV-2 infection
Authors: Nabi-Afjadi Mohsen , Karami Hadis , Goudarzi Kaveh , Alipourfard Iraj , Bahreini Elham
Published: November 2021

The concern of today's communities is to find a way to prevent or treat COVID-19 and reduce its symptoms in the patients. However, the genetic mutations and more resistant strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerge; the designed vaccines and adjuvant therapies would potentially control the symptoms and severity of COVID-19. The most important complication of this viral infection is acute respiratory distress syndrome, which occurs due to the infiltration of leukocytes into the alveoli and the raised cytokine storm. Interferons, as a cytokine family in the host, play an important role in the immune-related antiviral defense and have been considered in the treatment protocols of COVID-19. In addition, it has been indicated that some nutrients, including vitamin D, magnesium and zinc are essential in the modulation of the immune system and interferon (IFN) signaling pathway. Several recent studies have investigated the treatment effect of vitamin D on COVID-19 and reported the association between optimal levels of this vitamin and reduced disease risk. In the present study, the synergistic action of vitamin D, magnesium and zinc in IFN signaling is discussed as a treatment option for COVID-19 involvement.
Thymol-loaded PLGA nanoparticles: an efficient approach for acne treatment
Authors: Folle Camila , Marqués Ana M. , Díaz-Garrido Natalia , Espina Marta , Sánchez-López Elena , Badia Josefa , Baldoma Laura , Calpena Ana Cristina , García Maria Luisa
Published: November 2021

Background

Acne is a common skin disorder that involves an infection inside the hair follicle, which is usually treated with antibiotics, resulting in unbalanced skin microbiota and microbial resistance. For this reason, we developed polymeric nanoparticles encapsulating thymol, a natural active compound with antimicrobial and antioxidant properties. In this work, optimization physicochemical characterization, biopharmaceutical behavior and therapeutic efficacy of this novel nanostructured system were assessed.

Results

Thymol NPs (TH-NP) resulted on suitable average particle size below 200 nm with a surface charge around − 28 mV and high encapsulation efficiency (80%). TH-NP released TH in a sustained manner and provide a slow-rate penetration into the hair follicle, being highly retained inside the skin. TH-NP possess a potent antimicrobial activity against Cutibacterium acnes and minor effect towards Staphylococcus epidermis, the major resident of the healthy skin microbiota. Additionally, the stability and sterility of developed NPs were maintained along storage.

Conclusion

TH-NP showed a promising and efficient alternative for the treatment of skin acne infection, avoiding antibiotic administration, reducing side effects, and preventing microbial drug resistance, without altering the healthy skin microbiota. Additionally, TH-NP enhanced TH antioxidant activity, constituting a natural, preservative-free, approach for acne treatment.

Graphical Abstract
Understanding socioeconomic differences in metabolic syndrome remission among adults: what is the mediating role of health behaviors?
Authors: Hoveling Liza A. , Liefbroer Aart C. , Bültmann Ute , Smidt Nynke
Published: November 2021

Background

Although the incidence of metabolic syndrome (MetS) strongly varies based on individuals’ socioeconomic position (SEP), as yet no studies have examined the SEP-MetS remission relationship. Our aim is to longitudinally assess the associations between SEP measures education, income and occupational prestige, and MetS remission, and whether these associations are mediated by health behaviors, including physical activity, smoking, alcohol intake and diet quality.

Methods

A subsample (n = 16,818) of the adult Lifelines Cohort Study with MetS at baseline was used. MetS remission was measured upon second assessment (median follow-up time 3.8 years), defined according to NCEP-ATPIII criteria. To estimate direct associations between SEP, health behaviors and MetS remission multivariable logistic regression analyses were used. To estimate the mediating percentages of health behaviors that explain the SEP-MetS remission relationship the Karlson-Holm-Breen method was used. Analyses were adjusted for age, sex, the other SEP measures and follow-up time.

Results

At the second assessment, 42.7% of the participants experienced MetS remission. Education and income were positively associated with MetS remission, but occupational prestige was not. The association between education and MetS remission could partly (11.9%) be explained by health behaviors, but not the association between income and MetS remission.

Conclusions

Individuals with higher education more often experienced remission from MetS, mainly because individuals with higher education were more likely to have healthier behaviors. However, individuals with higher income more often experienced MetS remissions, regardless of their health behaviors. The occupational prestige of individuals was not associated with MetS remission.
The effectiveness of digital interventions for increasing physical activity in individuals of low socioeconomic status: a systematic review and meta-analysis
Authors: Western Max J. , Armstrong Miranda E. G. , Islam Ishrat , Morgan Kelly , Jones Una F. , Kelson Mark J.
Published: November 2021

Background

Digital technologies such as wearables, websites and mobile applications are increasingly used in interventions targeting physical activity (PA). Increasing access to such technologies makes an attractive prospect for helping individuals of low socioeconomic status (SES) in becoming more active and healthier. However, little is known about their effectiveness in such populations. The aim of this systematic review was to explore whether digital interventions were effective in promoting PA in low SES populations, whether interventions are of equal benefit to higher SES individuals and whether the number or type of behaviour change techniques (BCTs) used in digital PA interventions was associated with intervention effects.

Methods

A systematic search strategy was used to identify eligible studies from MEDLINE, Embase, PsycINFO, Web of Science, Scopus and The Cochrane Library, published between January 1990 and March 2020. Randomised controlled trials, using digital technology as the primary intervention tool, and a control group that did not receive any digital technology-based intervention were included, provided they had a measure of PA as an outcome. Lastly, studies that did not have any measure of SES were excluded from the review. Risk of Bias was assessed using the Cochrane Risk of Bias tool version 2.

Results

Of the 14,589 records initially identified, 19 studies were included in the final meta-analysis. Using random-effects models, in low SES there was a standardised mean difference (SMD (95%CI)) in PA between intervention and control groups of 0.06 (− 0.08,0.20). In high SES the SMD was 0.34 (0.22,0.45). Heterogeneity was modest in both low (I2 = 0.18) and high (I2 = 0) SES groups. The studies used a range of digital technologies and BCTs in their interventions, but the main findings were consistent across all of the sub-group analyses (digital interventions with a PA only focus, country, chronic disease, and duration of intervention) and there was no association with the number or type of BCTs.

Discussion

Digital interventions targeting PA do not show equivalent efficacy for people of low and high SES. For people of low SES, there is no evidence that digital PA interventions are effective, irrespective of the behaviour change techniques used. In contrast, the same interventions in high SES participants do indicate effectiveness. To reduce inequalities and improve effectiveness, future development of digital interventions aimed at improving PA must make more effort to meet the needs of low SES people within the target population.
The role of dendritic cells and their interactions in the pathogenesis of antibody-associated autoimmune encephalitis
Authors: Ismail Fatme Seval , Meuth Sven G. , Melzer Nico
Published: November 2021

Autoimmune encephalitis (AE) is an inflammatory brain disease which is frequently associated with antibodies (Abs) against cell-surface, synaptic or intracellular neuronal proteins. There is increasing evidence that dendritic cells (DCs) are implicated as key modulators in keeping the balance between immune response and tolerance in the CNS. Migratory features of DCs to and from the brain are linked to initiating and maintaining of neuroinflammation. Genetic polymorphisms together with other triggers such as systemic or cerebral viral infection, or systemic malignancies could contribute to the dysbalance of “regulatory” and “encephalitogenic” DCs with subsequent dysregulated T and B cell reactions in AE. Novel in vivo models with implantation of mature DCs containing neuronal antigens could help to study the pathogenesis and perhaps to understand the origin of AE. Investigations of DCs in human blood, lymphoid tissues, CSF, and brain parenchyma of patients with AE are necessary to deepen our knowledge about the complex interactions between DCs, T and B cells during neuroinflammation in AE. This can support developing new therapy strategies.
Anti-viral and pro-inflammatory functions of Toll-like receptors during gamma-herpesvirus infections
Authors: Gaglia Marta Maria
Published: November 2021

Toll-like receptors (TLRs) control anti-viral responses both directly in infected cells and in responding cells of the immune systems. Therefore, they are crucial for responses against the oncogenic γ-herpesviruses Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus and the related murine virus MHV68, which directly infect immune system cells. However, since these viruses also cause lifelong persistent infections, TLRs may also be involved in modulation of inflammation during latent infection and contribute to virus-driven tumorigenesis. This review summarizes work on both of these aspects of TLR/γ-herpesvirus interactions, as well as results showing that TLR activity can drive these viruses’ re-entry into the replicative lytic cycle.
Exploring the roles of HPV16 variants in head and neck squamous cell carcinoma: current challenges and opportunities
Authors: Cochicho Daniela , Gil da Costa Rui , Felix Ana
Published: November 2021

The incidence of squamous cell carcinomas of the head and neck (HNSCC) is consistently increasing, in association with human papillomavirus (HPV) infection, especially HPV16. HPV variants show heterogeneity in the pathogenicity of cervical cancer, but little has been established about their relevance on HNSCC. This review addresses the distribution of HPV16 variants in HNSCC and their potential contribution to clinical practice. A search was performed in PubMed using the keywords HNSCC HPV16 variants. Sixty articles were identified between 2000 and 2020 and 9 articles were selected for a systematic analysis. Clinical cohorts comprised 4 to 253 patients aged between 17 and 91 years with confirmed HPV16-positive HNSCC. Samples were collected from fresh biopsies of the tumour, oral rinse or formol fixed/paraffin embedded tissue, from the oral cavity, oropharynx, hypopharynx, larynx and Waldeyer's tonsillar ring. HPV16 variants were identified using Sanger sequencing techniques. Seven studies addressed the HPV16 E6 gene, one studied E6 and E7, another studied L1 and one focused on the long control region. European variants represent 25–95%, Asian-American 5–57% and African 2–4% of the total isolates, suggesting a marked predominance of European strains. No correlations could be drawn with patient prognosis, partly because many studies relied on small patient cohorts. Additional studies are needed, particularly those employing next generation sequencing techniques (NGS), which will allow faster and accurate analysis of large numbers of samples.
A novel model of acquired hydrocephalus for evaluation of neurosurgical treatments
Authors: McAllister James P. , Talcott Michael R. , Isaacs Albert M. , Zwick Sarah H. , Garcia-Bonilla Maria , Castaneyra-Ruiz Leandro , Hartman Alexis L. , Dilger Ryan N. , Fleming Stephen A. , Golden Rebecca K. , Morales Diego M. , Harris Carolyn A. , Limbrick David D.
Published: November 2021

Background

Many animal models have been used to study the pathophysiology of hydrocephalus; most of these have been rodent models whose lissencephalic cerebral cortex may not respond to ventriculomegaly in the same way as gyrencephalic species and whose size is not amenable to evaluation of clinically relevant neurosurgical treatments. Fewer models of hydrocephalus in gyrencephalic species have been used; thus, we have expanded upon a porcine model of hydrocephalus in juvenile pigs and used it to explore surgical treatment methods.

Methods

Acquired hydrocephalus was induced in 33–41-day old pigs by percutaneous intracisternal injections of kaolin (n = 17). Controls consisted of sham saline-injected (n = 6) and intact (n = 4) animals. Magnetic resonance imaging (MRI) was employed to evaluate ventriculomegaly at 11–42 days post-kaolin and to plan the surgical implantation of ventriculoperitoneal shunts at 14–38-days post-kaolin. Behavioral and neurological status were assessed.

Results

Bilateral ventriculomegaly occurred post-induction in all regions of the cerebral ventricles, with prominent CSF flow voids in the third ventricle, foramina of Monro, and cerebral aqueduct. Kaolin deposits formed a solid cast in the basal cisterns but the cisterna magna was patent. In 17 untreated hydrocephalic animals. Mean total ventricular volume was 8898 ± 5917 SD mm3at 11–43 days of age, which was significantly larger than the baseline values of 2251 ± 194 SD mm3for 6 sham controls aged 45–55 days, (p < 0.001). Past the post-induction recovery period, untreated pigs were asymptomatic despite exhibiting mild-moderate ventriculomegaly. Three out of 4 shunted animals showed a reduction in ventricular volume after 20–30 days of treatment, however some developed ataxia and lethargy, from putative shunt malfunction.

Conclusions

Kaolin induction of acquired hydrocephalus in juvenile pigs produced an in vivo model that is highly translational, allowing systematic studies of the pathophysiology and clinical treatment of hydrocephalus.
Primary breast CD20-positive extranodal NK/T cell lymphoma with stomach involvement: a case report and literature review
Authors: Zhang Ying , Wang Kuansong , Tan Qian , Yang Keda , Wu Dengshu , Xu Yajing , Zhao Xielan , Jiang Zhiping
Published: November 2021

Background

We present a unique case of primary breast CD20-positive extranodal NK/T cell lymphoma with stomach involvement in a young Chinese female patient.

Case presentation

The patient presented with a mass in her right breast that rapidly increased in size over approximately 2 months. Upper gastrointestinal endoscopy showed a giant serpentine ulcer in the stomach. Biopsy was performed, and microscopic inspection revealed that the fibrous tissue was diffusely involved by medium to large abnormal lymphocytes. The cytoplasm was low to moderate. The tumor cells had irregular nuclei and inconspicuous nucleoli. The lymphoid cells were strongly immunoreactive to CD20, CD3, CD4, CD56, TIA-1, EBER, and Ki-67 (90%). Epstein-Barr virus genomes were also found in tumor cells by in situ hybridization. A whole-body positron emission tomography (PET)-CT scan revealed intense FDG uptake in the right breast and greater curvature of the stomach. Monoclonal rearrangements of the T cell receptor (TCR-γ) and immunoglobulin heavy chain (IgH) were identified by genetic analysis. Whole-genome next-generation sequencing was performed, and up to 12 gene mutations, including a frameshift mutation in exon 4 of the BCOR (G97Rfs*87; 44.3%) gene and a base substitution mutation (Q61H 17.6%) in exon 3 of the KRAS gene, were detected. Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed using the database for annotation, visualization, and integrated discovery, which showed that rare primary breast CD20-positive extranodal NK/T cell lymphoma had a unique genetic background compared with diffuse large B cell lymphoma and extranodal NK/T cell lymphoma without CD20 expression. The patient received four cycles of the modified SMILE regimen. The second whole-body PET-CT scan revealed that the right breast mass was significantly smaller than before; additionally, FDG uptake in the stomach wall disappeared.

Conclusions

Systemic examination, extensive immunohistochemistry, and molecular profiling are essential for an accurate diagnosis. More similar cases are required to clarify the biological pathways and even the potential molecular mechanisms of rare lymphomas, which may help direct further treatment.
Impact of low-dose calcipotriol ointment on wound healing, pruritus and pain in patients with dystrophic epidermolysis bullosa: A randomized, double-blind, placebo-controlled trial
Authors: Guttmann-Gruber Christina , Piñón Hofbauer Josefina , Tockner Birgit , Reichl Victoria , Klausegger Alfred , Hofbauer Peter , Wolkersdorfer Martin , Tham Khek-Chian , Lim Seong Soo , Common John E. , Diem Anja , Ude-Schoder Katharina , Hitzl Wolfgang , Lagler Florian , Reichelt Julia , Bauer Johann W. , Lang Roland , Laimer Martin
Published: November 2021

Background

Wound management is a critical factor when treating patients with the inherited skin fragility disease dystrophic epidermolysis bullosa (DEB). Due to genetic defects in structural proteins, skin and mucous epithelia are prone to blistering and chronic wounding upon minor trauma. Furthermore, these wounds are commonly associated with excessive pruritus and predispose to the development of life-threatening squamous cell carcinomas, underscoring the unmet need for new therapeutic options to improve wound healing in this patient cohort. Vitamin D3 is acknowledged to play an important role in wound healing by modulating different cellular processes that impact epidermal homeostasis and immune responses. In this study, we evaluate the safety and efficacy of low-dose calcipotriol, a vitamin D3 analogue, in promoting wound healing and reducing itch and pain in patients with DEB.

Methods

Eligible DEB patients, aged ≥ 6 years and with a known mutation in the COL7A1 gene, were recruited to a placebo-controlled, randomized, double blind, cross-over phase II monocentric clinical trial. Patients were required to have at least two wounds with a minimum size of 6 cm2 per wound. The primary objective was to evaluate efficacy of daily topical application of a 0.05 µg/g calcipotriol ointment in reducing wound size within a 4-week treatment regimen. Secondary objectives were to assess safety, as well as the impact of treatment on pruritus, pain, and bacterial wound colonization in these patients.

Results

Six patients completed the clinical trial and were included into the final analysis. Topical low-dose calcipotriol treatment led to a significant reduction in wound area at day 14 compared to placebo (88.4% vs. 65.5%, P < 0.05). Patients also reported a significant reduction of pruritus with calcipotriol ointment compared to placebo over the entire course of the treatment as shown by itch scores of 3.16 vs 4.83 (P < 0.05) and 1.83 vs 5.52 (P < 0.0001) at days 14 and 28, respectively. Treatment with low-dose calcipotriol did not affect serum calcium levels and improved the species richness of the wound microbiome, albeit with no statistical significance.

Conclusions

Our results show that topical treatment with low-dose calcipotriol can accelerate wound closure and significantly reduces itch, and can be considered a safe and readily-available option to improve local wound care in DEB patients.

TrialRegistration EudraCT: 2016–001,967-35. Registered 28 June 2016, https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001967-35/AT
Molecular motor KIF3B in the prelimbic cortex constrains the consolidation of contextual fear memory
Authors: Joseph Nadine F. , Zucca Aya , Wingfield Jenna L. , Espadas Isabel , Page Damon , Puthanveettil Sathyanarayanan V.
Published: November 2021

Molecular and cellular mechanisms underlying the role of the prelimbic cortex in contextual fear memory remain elusive. Here we examined the kinesin family of molecular motor proteins (KIFs) in the prelimbic cortex for their role in mediating contextual fear, a form of associative memory. KIFs function as critical mediators of synaptic transmission and plasticity by their ability to modulate microtubule function and transport of gene products. However, the regulation and function of KIFs in the prelimbic cortex insofar as mediating memory consolidation is not known. We find that within one hour of contextual fear conditioning, the expression of KIF3B is upregulated in the prelimbic but not the infralimbic cortex. Importantly, lentiviral-mediated knockdown of KIF3B in the prelimbic cortex produces deficits in consolidation while reducing freezing behavior during extinction of contextual fear. We also find that the depletion of KIF3B increases spine density within prelimbic neurons. Taken together, these results illuminate a key role for KIF3B in the prelimbic cortex as far as mediating contextual fear memory.
Measuring the effects of nurse practitioner (NP)-led care on depression and anxiety levels in people with multiple sclerosis: a study protocol for a randomized controlled trial
Authors: Smyth Penelope , Watson Kaitlyn E. , Tsuyuki Ross T.
Published: November 2021

Background

Canada has one of the highest rates of multiple sclerosis (MS) in the world. Treatments and supports for people with MS (PwMS) have become increasingly complex, requiring individualized and adaptive care. Specialized NPs provide advanced skills to those with complex medical conditions, with potential to enhance the health, functioning, and quality of life for PwMS. This study aims to determine the effect of a Nurse Practitioner (NP) on depression and anxiety levels in PwMS.

Methods

We will perform a parallel randomized controlled trial. PwMS who are followed by general private-practice neurologists will be randomly assigned to the intervention group (NP-led care) or the ‘usual care’ control group (general neurologist or family physician and registered nurse support). In the intervention group, the NP will assess and provide care to the MS patient and their caregiver at a baseline visit, with 3-month and 6-month follow-up visits. PwMS in the control group will receive usual care provided by their community neurologists or family physicians with the standard assistance provided by registered nurses experienced in MS care. The primary outcome will be the difference in change in the patient’s anxiety and depression scores as measured by the validated Hospital Anxiety and Depression Scale (HADS) questionnaire at 3 months. Secondary outcomes will include difference in change in HADS at 6 months; Modified Fatigue Impact Scale scores (MSIF) at 3 and 6 months; EQ-5D scores at 3 and 6 months; caregiver health-related quality of life in MS measures (CAREQOL-MS) at 3 and 6 months; number of visits and phone calls to healthcare professionals recorded by patient, and satisfaction with NP-led care vs usual care measured by the validated Consultant Satisfaction Questionnaire.

Discussion

Findings from this study will contribute to exploring benefits of advanced nursing practitioner interventions for PwMS followed by general neurologists and family physicians in a community setting. It will provide evidence of the benefits of NP-led care for PwMS and offer an alternative healthcare resource for management of MS.

Trial registration

ClinicalTrials.govPro00069595. Retrospectively registered on June 26, 2020. Protocol version: January 2017, version 1.
Definitions and elements of endpoints in phase III randomized trials for the treatment of COVID-19: a cross-sectional analysis of trials registered in ClinicalTrials.gov
Authors: Sakamaki Kentaro , Uemura Yukari , Shimizu Yosuke
Published: November 2021

Background

There are several challenges in designing clinical trials for the treatment of novel infectious diseases, such as COVID-19. In particular, the definition of endpoints related to the severity, time frame, and clinical course remains unclear. Therefore, we conducted a cross-sectional analysis of phase III randomized trials for COVID-19 registered at ClinicalTrials.gov.

Methods

We collected the data from ClinicalTrials.gov on March 31, 2021, by specifying the following search conditions under Advanced Search: Condition or disease: (COVID-19) OR (SARS-CoV-2); Study type: Interventional Studies; Study Results: All Studies; Recruitment: Not yet recruiting, Recruiting, Enrolling by invitation, Active, Not recruiting, Suspended, Completed; Sex: All; and Phase: Phase 3. From the downloaded search results, we selected trials that met the following criteria: Primary Purpose: Treatment; Allocation: Randomized. We manually transcribed information not included in the downloaded file, such as Primary Outcome Measures, Secondary Outcome Measures, Time Frame, and Inclusion Criteria. In the analysis, we examined primary and secondary endpoints in trials with severe and non-severe patients, including the types of endpoints, time frame, clinical course, and sample size.

Results

A total of 406 trials were included in the analysis. The median numbers of endpoints in trials with severe and non-severe patients were 9 and 7, respectively. Approximately 25% of the trials used multiple primary endpoints. Regardless of the type of endpoint, the time frames were longer in the trials with severe patients than in the trials with non-severe patients. In the evaluation of the clinical course, worsening was often considered in binary endpoints, and improvement was considered in time-to-event endpoints. The sample size was the largest in clinical trials using binary endpoints.

Conclusions

Endpoints can differ with respect to severity, and the clinical course and time frame are important for defining endpoints. This study provides information that can facilitate the achievement of a consensus for the endpoints in evaluating COVID-19 treatments.