bluuebunny/crossref_metadata_2025 huggingface dataset:
P11 Evaluation of in vitro activity of double β-lactam therapy and relationship with PBP activity in Escherichia coli isolates
Authors: Suich J , Van der Woude M , Wearmouth D , Burns P , Barlow G
Published: June 2022

Background

PBPs are involved in the construction of peptidoglycan, which is the major constituent of bacterial cell walls and the target of β-lactam antibiotics. There is little published research analysing the relationship between β-lactams with differing bacterial PBP targets and how they can be manipulated in combinations with respect to clinical or microbiological (e.g. resistance) outcomes (i.e. does expanded PBP activity via a combination lead to better in vitro/in vivo outcomes).

Objectives

To systematically explore the relationship between double β-lactam therapy (with and without at least one partner being a β-lactamase inhibitor antibiotic such as co-amoxiclav) and in vitro activity against susceptible Escherichia coli strains.

Methods

We systematically explored the relationship between double β-lactam therapy combinations against seven E. coli strains of variable resistance in vitro. This included fully susceptible isolates, ESBL producers and carbapenemase producers (CPEs). For each of 10 antibiotics, the MIC was determined individually, and subsequently in combination with 9 further antibiotics, using the MTS™ ‘cross’ synergy method (Liofilchem, 2012).

Results

Overall, 86/630 (13.6%) of all combinations tested showed synergy and 408/630 (64.8%) were additive; 136/630 (21.6%) combinations showed indifference. Of the 86 ‘bug–drug’ combinations that showed synergy, 42/86 (49%) included ceftazidime/avibactam, representing 42/126 (33%) of all ceftazidime/avibactam-based combinations tested, and 56/86 (65%) of synergistic combinations covered PBP2. Synergy was most commonly detected in ESBL producers (58/86; 67% of combinations) and less frequently seen in CPEs (2/86; 2% of combinations) and fully susceptible isolates (8/86; 9% of combinations). Additive effects were seen in 92/180 (51%) combinations versus ESBLs, compared with 18/90 (20%) in CPEs, versus 154/180 (86%) in fully susceptible isolates. No antagonism was identified with any antibiotic combination.

Conclusions

In the combinations tested, synergy or additive effects were common (78%); similar to our previous work with fosfomycin/β-lactam combinations (89%), but higher than we found with fosfomycin/non-β-lactam combinations (28%). Many of the synergistic bug–drug combinations identified contained a β-lactam inhibitor as a partner and/or provided PBP2 activity. This provisionally suggests a role for PBP2 (also targeted by avibactam) in synergy, although the presence of a β-lactamase inhibitor may also be important. Confirmation using an alternative method and mechanistic elucidation is required. The clinical/microbiological importance of such effects remains unclear.
P16 Strengthening surveillance systems for antimicrobial resistance in urinary tract infections in Kenya
Authors: Bartonjo G , Ngata E , Revathi G , Aiken A
Published: June 2022

Background

Urinary tract infections (UTIs) are amongst the most common conditions leading to outpatient visits and are also one of the most common causes of inappropriate antibiotic usage. Addressing antimicrobial resistance (AMR) requires strengthening surveillance system in Kenya where UTI is a problem with health systems having limited capacity for accurate laboratory identification of UTI pathogens. Empirical treatment to manage UTIs is the most common problem due to limited microbiology capacity. These include shortages of suitable training, equipment, quality control procedures and professional expertise to make an accurate clinical interpretation of urine cultures. This leads to reporting normal flora as pathogens.

Objectives

To deliver training on the identification and antibiotic susceptibility testing of bacterial isolates from urine infections at participating hospitals in the Kenyan AMR surveillance network and measure competency levels in staff participating in the training with the aim of strengthening the Kenyan surveillance system.

Methods

A 1 day baseline visit to the five sites was made between October and November 2021 using a standardized checklist to assess laboratory capacity. This was followed by urine processing training conducted between November 2021 and January 2022 in Malindi, Jaramogi, Kitale, Nakuru and Nyeri County Hospitals. Training materials were developed with the input of Aga Khan University Hospital. A 5 day in-person training course was delivered at each of the five hospitals, which targeted an average of 2–3 laboratory staff per hospital. The competencies of the laboratory staff were assessed by written pre-assessment and post-assessment tests. A standardized practical assessment was achieved by use of five different control organisms. The scores were done by doing an average performance score at each hospital laboratory.

Results

Out of 13 trainees, 8 were male and 5 were female. The median number of years since qualification for these staff was 6 (IQR 2–9). The median number of total months of microbiology training time was 2.3 (IQR 1–7). The median pre-training and post-training scores were 46% and 90%, respectively; non-parametric Wilcoxon rank test showed statistical difference (P < 0.0001) between pre-training and post-training. All participants improved from pre-to post- training assessment from the 5 day training with marked improvement amongst from staff with lowest previous level of laboratory training.

Conclusions

Training microbiology staff in the accurate processing of urine sample will be an important activity for a Kenyan AMR surveillance system. These training materials, if delivered by an experienced trainer, can achieve a clear improvement in knowledge levels and practical competence for real-life microbiology identifications.
P17 Quality assurance in bacterial identification and antimicrobial susceptibility testing results: an essential component of antimicrobial resistance surveillance
Authors: Githii Susan , Kahura Jedida , Zawadi Mercy , Muchiri George , Waswa Ethel , Stabler Richard
Published: June 2022

Background

Antimicrobial resistance (AMR) is a major threat to human health. Bacterial identification and antibiotic susceptibility testing play an essential role in patient care and control of antibiotic resistance mechanisms by indicating which antibiotics are most likely to treat an infection, reducing the empirical prescription of broad-spectrum antibiotics and avoiding the unnecessary prescription of antibiotics to reduce healthcare costs. AMR surveillance in Kenya has historically been focused on pathogens that cause significant mortality and morbidity such as diarrhoea illnesses and bacteraemia. Many private hospitals and a few public hospitals in Kenya have the capacity to conduct antimicrobial susceptibility testing; however, the available data are rarely verified for quality.

Methods

This study was conducted in five sentinel sites in Kenya. Clinical samples were processed in the sites as part of routine microbiology. Each sentinel site selected isolates as per the National AMR sample referral guide and sent them to the National Microbiology Reference Laboratory (NMRL) for quality assessment. Upon reception of isolates at NMRL, they were subcultured and subjected to organism identification testing using MALDI-TOF equipment. Antimicrobial susceptibility testing was performed using Vitek 2 compact. In case of any discrepancy on organism identification, correct antibiotic selection and resistance interpretation, the sites were informed.

Results

Antimicrobial susceptibility testing was conducted on Escherichia coli and Staphylococcus aureus, which were the most frequently isolated pathogens. High resistance to cephalosporins was observed with the E. coli isolates. Over 80% susceptibility of E. coli to amikacin, ampicillin, gentamicin, meropenem, nitrofurantoin and piperacillin/tazobactam was observed. This shows that the antibiotics can be used for empirical therapy in areas where there is no laboratory capacity for antibiotic susceptibility testing. Resistance to gentamicin of S. aureus isolates was found to be 10%, which shows that gentamicin still finds a role in controlling S. aureus infections. Penicillin resistance in S. aureus was 100%. High levels of resistance were observed with erythromycin (61%) and ampicillin (84%)

Conclusions

There is no site that scored 100% in pathogen identification and drug–bug combination. Continuous capacity building of AMR surveillance sites through mentorships to improve quality of data generated is of paramount importance. E. coli and S. aureus were the most frequently isolated pathogens. High levels of resistance were observed with erythromycin (61%) and ampicillin (84%), which calls for antibiotic stewardship programmes to educate on optimal antibiotic use.
P19 A service evaluation to assess antimicrobial resistance in penicillin allergy
Authors: Ahmed S , Relton S , West R , Sandoe J
Published: June 2022

Background

Antibiotic consumption is one of the main drivers for antimicrobial resistance (AMR). To improve clinical outcomes and tackle AMR, we need to improve antibiotic usage in patients with penicillin allergy (PenA). Patients with PenA have been found to have higher antibiotic usage, often requiring repeated courses of antibiotics compared with those without PenA. Additionally, patients with PenA are more likely to receive broad spectrum antibiotics.

Objectives

To determine whether patients who have PenA are more likely to be colonized or infected with resistant bacteria.

Methods

Data were extracted from the pathology reporting system (Telepath) for blood culture specimens isolating Staphylococcus aureus and Streptococcus pneumoniae between 2017 and 2019 at Leeds Teaching Hospitals NHS Trust. Sputum samples from 2019 that isolated S. pneumoniae and Haemophilus influenzae were also analysed. These organisms/samples were chosen as these would indicate the presence of an infection where a penicillin would normally be used as first-line therapy. Where patients had multiple samples only the first sample obtained during the study period was included in the analysis. Standard descriptive statistics was used to summarize the data and characteristics were cross tabulated with penicillin allergy status.

Results

S. pneumoniae isolated from blood cultures: A total of 297 patients were included in the analysis, 33/297 (11.1%) had PenA, 50.8% were female and the median age was 60 years (IQR 37–75). Susceptibility results are summarized in Figure 1. Resistant isolates are comprised of isolates with resistant or intermediate susceptibility. S. aureus isolated from blood cultures: Analysis included 783 isolates from first patient encounters, 97/783 (12.4%) patients had PenA, 35.1% were female and the median age was 58 years (IQR 39–74.5). Susceptibility results are summarized in Figure 2. S. pneumoniae isolated from sputum: A total of 156 isolates were included in the final analysis: 29/156 (18.6%) patients had PenA, 53.3% were female and the median age was 67 years. Susceptibility results are summarized in Figure 3. H. influenzae isolated from sputum: A total 719 samples were included, 122/719 (15.8%) patients had PenA, 55.9% were female and median age was 67 years. Susceptibility results are summarized in Figure 4.

Conclusions

PenA prevalence differs across different patient populations. A higher proportion of patients with PenA had resistance in S. pneumoniae sputum isolates compared with those without, however this finding did not meet statistical significance. Further studies evaluating the impact of PenA on AMR need to be conducted.
Cyber Solace: Historicizing an Online Forum for Patients with Depression, 1990-1999
Authors: Huang Daniel
Published: June 2022

Alt.support.depression (ASD) was an online forum for patients with depression that operated in the 1990s on the computer network Usenet. At its peak, the forum had an estimated readership of 57,000 and saw upwards of 500 posts a day. Aligning with recent efforts by historians to deinstitutionalize the history of psychiatry, this study traces the emergence of ASD as a new extramural space for mental health care in the 1990s. Its users created a unique therapeutic milieu informed by the consumer-survivor movement and 1990s cyberculture. As ASD grew in size and complexity, its users sought to redesign their forum, opening what had previously been a technological black box. Working by a process of inscription—a concept described by science and technology studies scholar Madeleine Akrich—they created a unique psychiatric constituency whose attitude towards technologies of mental health care was neither submissive nor subversive. Rather, the forum’s users developed their own notions of patient empowerment and lay expertise in psychiatry.
Professional Jurisdictions and Intraprofessional Identity Dynamics: Doctors of Osteopathic Medicine and the Doctors of General Medicine
Authors: Tsai Gawin , Veazey Brooks Joanna
Published: June 2022

Professional jurisdictional boundaries change throughout time due to a myriad of factors such as scientific advances, social changes, or governmental requirements. Research on the negotiation of these jurisdictional changes has primarily focused on the relational dynamics between professions that affect these boundaries. We examine two physician groups that considered jurisdictional changes which were initially antithetical to their core professional identity. The DOs grappled with whether or not to incorporate drug therapy into their practice, and generalist MDs had to decide whether or not to become a specialty. We find that jurisdictional negotiations also occur within a profession, not just between them. We argue that for a profession to pursue a change in scope, members must settle on an interpretation of their professional identity congruent with the potential jurisdictional change.
Efficient extracellular production of recombinant proteins in E. coli via enhancing expression of dacA on the genome
Authors: Yang Haiquan , Wang Haokun , Wang Fuxiang , Zhang Kunjie , Qu Jinfeng , Guan Jianmin , Shen Wei , Cao Yu , Xia Yuanyuan , Chen Xianzhong
Published: June 2022

D, D-carboxypeptidase DacA plays an important role in the synthesis and stabilization of Escherichia coli cell wall peptidoglycan. The production level of extracellular recombinant proteins in E. coli can be enhanced by high D, D-carboxypeptidase activity. Construction of expression systems under optimal promoters is one of the main strategies to realize high protein production in E. coli. In this study, the promoter PdacA-3 from DacA on the genome of E. coli BL21 (DE3) was verified to be efficient for recombinant green fluorescent protein using the plasmid mutant pET28a-PdacA with PdacA-3. Meanwhile, the promoter PdacA-3 was engineered to increase the production level of proteins via inserting one or two Shine–Dalgarno (SD) sequences between the promoter PdacA-3 and the target genes. The expression level of dacA on the genome was increased by the improved transcription of the engineered promoters (especially after inserting one additional SD sequence). The engineered promoters increased cell membrane permeabilities to significantly enhance the secretion production of extracellular recombinant proteins in E. coli. Among them, the extracellular recombinant amylase activities in E. coli BL21::1SD-pET28a-amyK and E. coli BL21::2SD-pET28a-amyK were increased by 2.0- and 1.6-fold that of the control (E. coli BL21-pET28a-amyK), respectively. Promoter engineering also affected the morphology and growth of the E. coli mutants. It was indicated that the engineered promoters enhanced the expression of dacA on the genome to disturb the synthesis and structural stability of cell wall peptidoglycans.
The Anopheles lindesayi Species Complex (Diptera: Culicidae) in Bhutan
Authors: Somboon Pradya , Phanitchakun Thanari , Namgay Rinzin , Harbach Ralph E
Published: June 2022

This paper deals with species A, C, D, and E of the Lindesayi Complex of Anopheles subgenus Anopheles (Diptera: Culicidae) that were recently recorded from Bhutan. Species B is not included due to insufficient data. Species A is Anopheles lindesayi sensu stricto, and species C, D, and E are new species that are formally described and named herein as Anopheles druki Somboon, Namgay & Harbach, Anopheles himalayensis Somboon, Namgay & Harbach and Anopheles thimphuensis Somboon, Namgay & Harbach, respectively. Morphological characteristics of the adults, larval and pupal stages of each species are provided and compared with An. lindesayi from Bhutan.
A case of an air gun bullet paranasal sinuses injury in an 11-year-old male
Authors: Georgolios Alexandros , Brestel Andrea , Childers Adrienne
Published: June 2022

Non-powder firearms, such as BB guns, are considered safer than traditional firearms and are often marketed toward younger demographics as children’s toys. Recent advances in compressed-gas technology have drastically increased the firing power of these types of firearms, which has caused them to be more dangerous and capable of causing severe injury. We report the case of an 11-year-old male admitted for nasal injury caused by a BB gun pellet. The projectile had an unpredictable course: it pierced the skin of his left nasal sidewall, traversed through the soft tissues of the nose to the right nasal cavity violating the posterior septum, and lodged in the right posterior ethmoids adjacent to the posterior attachment of the middle turbinate. The metallic foreign object was successfully retrieved from the right nasal cavity via an endoscopic approach after minimal endoscopic dissection, guided by the preoperative radiologic imaging.
distAngsd: Fast and Accurate Inference of Genetic Distances for Next-Generation Sequencing Data
Authors: Zhao Lei , Nielsen Rasmus , Korneliussen Thorfinn Sand
Published: June 2022

Commonly used methods for inferring phylogenies were designed before the emergence of high-throughput sequencing and can generally not accommodate the challenges associated with noisy, diploid sequencing data. In many applications, diploid genomes are still treated as haploid through the use of ambiguity characters; while the uncertainty in genotype calling—arising as a consequence of the sequencing technology—is ignored. In order to address this problem, we describe two new probabilistic approaches for estimating genetic distances: distAngsd-geno and distAngsd-nuc, both implemented in a software suite named distAngsd. These methods are specifically designed for next-generation sequencing data, utilize the full information from the data, and take uncertainty in genotype calling into account. Through extensive simulations, we show that these new methods are markedly more accurate and have more stable statistical behaviors than other currently available methods for estimating genetic distances—even for very low depth data with high error rates.
ZIP14 is involved in iron deposition and triggers ferroptosis in diabetic nephropathy
Authors: Wu Keping , Fei Lingyan , Wang Xiaohua , Lei Yan , Yu Liu , Xu Wenqian , Chen Jiasi , Zhu Enyi , Zhong Ming , Huang Mingcheng , Xi Jiang , Yin Fei , Yan Zhijun , Zhao Xinying , Tang Chun , Patzak Andreas , Liu Xiaoping , Zheng Zhihua
Published: June 2022

Ferroptosis is caused by lipid peroxidation and iron accumulation and can cause cell death. Abnormally expressed iron transporters are involved in ferroptosis in a variety of diseases. ZRT/IRT-like protein 14 (ZIP14) is a transport protein that can mediate cellular uptake of iron, zinc, and manganese. Herein, we have tested the hypothesis that the divalent metal transporter ZIP14 is involved in the initiation of ferroptosis in diabetic nephropathy (DN). DN was induced in 8-week-old male rats by streptozotocin before analysis of the degree of renal tubular injury. In addition, an in vitro model of DN in human kidney proximal tubular cell line was used. We showed that ZIP14 was up-regulated and ferrous iron (Fe2+) levels increased both in vivo and in vitro. Expression of glutathione peroxidase 4 and the level of glutathione were reduced, whereas that of malondialdehyde (MDA) increased. Ferrostatin-1 (Fer-1) treatment reduced the expression of ZIP14 and the levels of Fe2+ and MDA, which is consistent with ferroptosis. Fer-1 improved kidney function in DN rats. This was characterized by urine levels of protein-to-creatinine ratio, α1-microglobulin, and N-acetyl-β-D-glucosaminidase. Our study demonstrates a novel role for ZIP14 in diabetic kidney injury mediated by ferroptosis, and suggests a potential new therapeutic approach for the treatment of diabetic nephropathy.
Bioconjugated chelates based on (methylpyridinyl)tacn: synthesis, 64Cu labeling and in vitro evaluation for prostate cancer targeting
Authors: Marlin Axia , Hierlmeier Ina , Guillou Amaury , Bartholomä Mark , Tripier Raphaël , Patinec Véronique
Published: June 2022

Three new bifunctional copper chelators based on the 1,4,7-triazacyclononane (tacn) platform have been synthesized and conjugated to peptides. The first one is constituted of the tacn with two methylpyridinyl and one methylthiazolyl carboxylic acid pendant arms, while, in the second and third ones, the macrocycle is functionalized by three methylpyridinyl groups, with an additional hexynoic acid chain on a carbon of one or two pyridine rings. These three bifunctional chelators have been conjugated to the antagonist DPhe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 peptide for targeting the gastrin-releasing peptide receptor, which is overexpressed in prostate cancer. The resulting monomeric bioconjugates have shown their efficiency to be radiolabeled with β+ emitter 64Cu, and the hydrophilicity and PC-3 cell internalization properties of these radiolabeled conjugates have been studied. PC-3 cell binding affinity of mono- and dimeric metal-free and natCu metallated conjugates have been evaluated by IC50 measurements. The results demonstrate the potential of these methylpyridinyl tacn derivatives for radiopharmaceutical applications.
UG/Abi: a highly diverse family of prokaryotic reverse transcriptases associated with defense functions
Authors: Mestre Mario Rodríguez , Gao Linyi Alex , Shah Shiraz A , López-Beltrán Adrián , González-Delgado Alejandro , Martínez-Abarca Francisco , Iranzo Jaime , Redrejo-Rodríguez Modesto , Zhang Feng , Toro Nicolás
Published: June 2022

Reverse transcriptases (RTs) are enzymes capable of synthesizing DNA using RNA as a template. Within the last few years, a burst of research has led to the discovery of novel prokaryotic RTs with diverse antiviral properties, such as DRTs (Defense-associated RTs), which belong to the so-called group of unknown RTs (UG) and are closely related to the Abortive Infection system (Abi) RTs. In this work, we performed a systematic analysis of UG and Abi RTs, increasing the number of UG/Abi members up to 42 highly diverse groups, most of which are predicted to be functionally associated with other gene(s) or domain(s). Based on this information, we classified these systems into three major classes. In addition, we reveal that most of these groups are associated with defense functions and/or mobile genetic elements, and demonstrate the antiphage role of four novel groups. Besides, we highlight the presence of one of these systems in novel families of human gut viruses infecting members of the Bacteroidetes and Firmicutes phyla. This work lays the foundation for a comprehensive and unified understanding of these highly diverse RTs with enormous biotechnological potential.
L’association entre la défavorisation matérielle par quartier et l’incidence d’hospitalisation chez les enfants infectés par le SRAS-CoV-2 à Montréal
Authors: Abda Assil , del Giorgio Francesca , Gauvin Lise , Autmizguine Julie , Kakkar Fatima , Drouin Olivier
Published: June 2022

Historique

Même si les facteurs sociodémographiques sont liés à l’infection par le SRAS-CoV-2 et aux hospitalisations chez les adultes, peu de données portent sur l’association entre ces caractéristiques et les hospitalisations attribuables au SRAS-CoV-2 chez les enfants. La présente étude visait à déterminer l’association entre la défavorisation matérielle par quartier et l’incidence d’hospitalisations à cause du SRAS-CoV-2 chez les enfants.

Méthodologie

Les chercheurs ont réalisé une étude de cohorte rétrospective de tous les enfants (de 0 à 17 ans) atteints d’une infection par le SRAS-CoV-2 confirmée par un test d’amplification en chaîne par polymérase après transcription inverse (PCR) entre le 1er mars et le 31 mai 2021 dans un hôpital pédiatrique de soins tertiaires de Montréal, au Canada. Ils ont colligé les données par examen des dossiers et ont inclus l’âge, le sexe et les codes postaux, afin de pouvoir lier la défavorisation matérielle à l’échelle de l’aire de diffusion, mesurée au moyen des quintiles de l’indice de défavorisation matérielle de Pampalon. Ils ont examiné l’association entre les quintiles de cet indice et les hospitalisations à l’aide de la régression de Poisson.

Résultats

Pendant la période de l’étude, 964 enfants ont reçu un résultat positif au SRAS-CoV-2 confirmé par un test PCR, et 124 d’entre eux ont été hospitalisés. Au total, 40,7 % des enfants hospitalisés habitaient dans le quintile le plus défavorisé d’après l’indice de défavorisation matérielle de Pampalon. Le rapport du taux d’incidence des hospitalisations dans ce groupe était de 2,42 (intervalle de confiance à 95 % : 1,33; 4,41) par rapport au quintile le plus privilégié.

Conclusion

Plus du double des enfants qui habitaient dans les quartiers les plus défavorisés sur le plan matériel étaient hospitalisés à cause de la COVID-19 par rapport à ceux qui habitaient dans les quartiers les plus privilégiés. Il faudrait déployer des efforts particuliers pour protéger les enfants qui habitent dans des quartiers défavorisés, particulièrement dans l’attente de la vaccination des plus jeunes.
Redeemable Platform Currencies
Authors: Rogoff Kenneth , You Yang
Published: June 2022

Can massive online retailers such as Amazon and Alibaba issue digital tokens that potentially compete with bank debit accounts? There is a long history of trading stamps and loyalty points, but new technologies are poised to sharply raise the significance of redeemable assets as a store of value. Here, we develop a simple stylized model of redeemable tokens that can be used to study sales and pricing strategies for issuing tokens, including ICOs. Our central finding is that platforms can potentially earn higher revenues by making tokens non-tradable unless they can generate a sufficiently high outside-platform convenience yield.
Market Power in Neoclassical Growth Models
Authors: Ball Laurence , Mankiw N Gregory
Published: June 2022

This article examines the optimal accumulation of capital and the effects of government debt in neoclassical growth models in which firms have market power and therefore charge prices above marginal cost. In this environment, the real interest rate earned by savers is less than the net marginal product of capital. We establish a new method for evaluating dynamic efficiency that can be applied in such economies. A plausible calibration suggests that the wedge between the real interest rate and the marginal product of capital is about 4 percentage points and that the US economy is dynamically efficient. In addition, government Ponzi schemes can have different implications for welfare than they do under competition. Even if the government can sustain a perpetual rollover of debt and accumulating interest, the policy may nonetheless reduce welfare by depressing steady-state capital and aggregate consumption. These findings suggest that even with low interest rates, as have been observed recently, fiscal policymakers should still be concerned about the crowding-out effects of government debt.
Assessment of dermal absorption of aluminium from a representative antiperspirant formulation using a (26Al)Al microtracer approach: a follow-up study in humans
Authors: de Ligt Rianne , Westerhout Joost , Grossouw Dimitri , Buters Thomas P , Rissmann Robert , Burggraaf Jacobus , Windhorst Albert D , Tozer Sarah , Pappa Gerlinde , Wall Brian , Bury Dagmar , Mason David R , Vaes Wouter H J
Published: June 2022

A follow-up study was performed in 12 healthy women to evaluate systemic exposure to aluminium following topical application of a representative antiperspirant formulation under real-life use conditions (part A) and to assess the local fate of topically applied aluminium by taking additional tape strips and skin biopsies (Part B). A simple roll-on formulation, containing the maximal possible radioactive dose, was prepared with [26Al] aluminium-labeled chlorohydrate (ACH). The microtracer of [26Al] was used to distinguish aluminium from the natural background, using accelerator mass spectrometry. [26Al] aluminiumcitrate was administered intravenously to estimate the dermal fraction absorbed. Despite the 25-fold increase of the topical dose compared with the previous study, only 12 blood samples gave results above the lower limit of quantitation (0.118 fg/mL). The most reliable estimates of the dermal fraction absorbed are derived from noncompartmental analysis with the urine data. By using the intravenous dose to normalize the urinary excretion to 100% bioavailability, the best estimate of the fraction absorbed of [26Al] from a topical application of [26Al]-aluminium-labeled chlorohydrate in an antiperspirant formulation was 0.00052%. Part B of the study demonstrated that the majority of the aluminium in the formulation remained associated with the external layers of the skin without penetration through the skin.
Survival of Xanthomonas fragariae on Common Materials
Authors: Turechek William W. , Winterbottom Christopher , Meyer-Jertberg Melody , Wang Hehe
Published: June 2022

Xanthomonas fragariae causes strawberry angular leaf spot (ALS), an important disease for the strawberry nursery industry in North America. To identify potential inoculum sources, the survival of X. fragariae was examined on the surfaces of 11 common materials found in nurseries: corrugated cardboard, cotton balls, cotton cloth (t-shirt), strawberry leaf, sheet metal, plastic, rubber, Tyvek, wood (balsa), glass (microscope slide), and latex (latex glove). Prefabricated rectangular samples (7.62 by 2.54 cm) of each material were immersed in a bacterial suspension for 15 min, after which the samples were stored at approximately 20°C (room temperature) or −4°C (the cold storage temperature for dormant plants in strawberry nurseries) for 1, 3, 7, 14, 30, 60, 90, 180, 270, and 365 days after inoculation (DAI). After the storage period elapsed, bacteria were recovered from the surfaces of each of the samples with phosphate-buffered saline (PBS)-soaked cotton balls. Survival rate was determined with a viability real-time quantitative PCR procedure and in a plant bioassay that involved rub inoculation of strawberry leaflets with the PBS-soaked cotton balls used to recover bacteria from the samples. Results showed that X. fragariae could survive on all surfaces but that survival rate differed among materials and storage temperature. All materials were capable of harboring viable bacteria up to 7 DAI when stored at −4°C based on the formation of lesions on inoculated leaves in the plant bioassay. The longest survival observed was 270 DAI on cardboard stored at −4°C. At room temperature, cardboard, cotton balls, cotton t-shirt, and strawberry leaf tissue supported small bacterial populations up to 14 DAI. The information from this study can be used to improve sanitation practices for ALS management in strawberry nurseries.
Multilocus Sequence Analysis Reveals New Hosts of Palm Lethal Decline Phytoplasmas in Florida, U.S.A.
Authors: Mou De-Fen , Helmick Ericka E. , Bahder Brian W.
Published: June 2022

Palm-infecting phytoplasmas have been a persistent threat to sustainable palm production in Florida, U.S.A., for nearly a century. First, lethal yellowing (LY) was introduced in the early 1900s, then lethal bronzing (LB) was introduced around 2006. While LY is currently rare in Florida, LB is actively spreading throughout the state and as it becomes more established, has begun infecting new host species. Continual monitoring efforts throughout the state seeks to catch infections and remove palms before further spread. As a result of this effort, many palms displaying a variety of symptoms are sampled and submitted to the University of Florida – Fort Lauderdale Research and Education Center (FLREC) for confirmation of phytoplasma infection status. Over the course of 3 years, multiple samples of Washingtonia robusta and Roystonea regia were submitted. All of these samples were negative for phytoplasma upon the initial qPCR screening and were tested with universal primers and confirmed as negative. Specimens of Arenga engleri, Rhapidophyllum hystrix, and Sabal palmetto were received and tested positive for LB, LB, and LY, respectively, tentatively representing new host records for these species and respective phytoplasma. Multilocus sequence analyses utilizing the 16S rRNA, 16S-23S intergenic spacer region, secA, secY, and groEL further confirmed the identity of LB and LY in the respective new hosts. These results highlight the need for continued monitoring of palms in Florida so that infected palms can be removed quickly. Also, the novel molecular data ( secY) help better understand and identify phytoplasmas in palms.
Trajectories of Dyspareunia From Pregnancy to 24 Months Postpartum
Authors: Rosen Natalie O. , Dawson Samantha J. , Binik Yitzchak M. , Pierce Marianne , Brooks Melissa , Pukall Caroline , Chorney Jill , Snelgrove-Clarke Erna , George Ronald
Published: June 2022

(Abstracted from Obstet Gynecol 2022;139(3):391–399)

Dyspareunia, defined as pain during vaginal intercourse, commonly affects women during pregnancy and the postpartum period. Although its prevalence has been extensively studied, the wide variability in prevalence estimates may be explained by heterogeneity in trajectories of dyspareunia, which have not been established.
Relationship Between Attitudes and Beliefs About Sleep, Sleep Disturbance, and Pain Interference in Patients With Spinal Pain
Authors: Neilson Brett D. , Shepherd Mark H. , Dickerson Chris , Chaconas Eric J. , Young Jodi L. , Rhon Daniel I.
Published: June 2022

Objectives:

Sleep impairments are a strong predictor of pain, making sleep a potential interest when treating patients with spine pain. Typical beliefs about the importance of sleep in patients seeking care for spinal pain are unknown. The purpose of this study was to describe the beliefs and attitudes about sleep in patients seeking care for spinal pain and to examine the relationships between dysfunctional beliefs and attitudes about sleep (DBAS), disordered sleep, and pain interference.

Materials and Methods:

This cross-sectional study included patients presenting to physical therapy with spine pain. Participants completed questionnaires including demographics, medical history, pain interference (pain, enjoyment, and general activity), DBAS-16, and sleep-related impairment (Patient-Reported Outcome Measurement Information System). Correlations were calculated between DBAS-16 scores and measures of sleep quality/quantity, and a generalized linear model was used to investigate the predictive ability of DBAS-16 scores on pain interference.

Results:

The mean DBAS-16 score was 4.22 (SD=2.03), with 52.5% of participants having DBAS. There was a strong relationship between DBAS-16 and Patient-Reported Outcome Measurement Information System (r
s=0.7; P<0.001). For every point higher score on the DBAS-16, pain interference scores increased by approximately half a point (B=0.46; 95% CI 0.33, 0.59, 1.80; P <0.001)

Discussion:

These results highlight a strong relationship between beliefs and attitudes about sleep and measures of sleep quality/quantity and a linear association with pain interference scores. These findings provide a rationale for targeting beliefs and attitudes about sleep when managing pain-related symptoms in patients seeking care for spine pain.
Verrucous Melanoma Presenting as a Cutaneous Horn
Authors: Bur Delfina , Thibodeaux Quinn , Keeling Brett
Published: June 2022

Verrucous malignant melanoma (MM) is a rare variant of melanoma that often presents diagnostic challenges. This case highlights the unique presentation of verrucous MM underlying a cutaneous horn. It is vital for dermatologists to be aware of this potentially benign-appearing variant to be able to diagnose and treat MM early on.
Late capsular blockage syndrome: Clinical and anterior segment optical coherence tomography characteristics
Authors: Yang Hsin-Yu , Kao Sui-Ching , Tsai Chieh-Chih , Yu Wei-Kuang
Published: June 2022

Background:

Late capsular blockage syndrome (CBS) is a rare phenomenon which is found after cataract surgery. The mechanism, anterior segment optical coherence tomography (OCT) presentation, and clinical characteristics are not well studied.

Methods:

We studied patients who developed late CBS in Taipei Veterans General Hospital from 2012 to 2019. Age, sex, systemic disease, ocular disease, interval between cataract surgery and CBS, axial length, type of intraocular lens implanted, grading of posterior capsular opacity, refraction, visual acuity, and anterior segment OCT findings were documented. Patients are categorized into two groups according to anterior segment OCT findings. All patients underwent Nd:YAG laser capsulotomy and were prescribed a low-dose topical steroid for 7 days. Postcapsulotomy refraction and visual acuity were recorded. All the clinical data were compared in the two groups.

Results:

This study included 18 eyes with late CBS. Patients’ median age was 80 (range, 54–92) years. The mean duration between cataract surgery and CBS diagnosis was 80.28 (range 15–136) months. According to anterior segment OCT findings, we subcategorized the patients into two groups: gravel appearance (n = 7) and milky (n = 11) appearance. After laser capsulotomy, mean visual acuity improved 0.18 ± 0.10 on the LogMAR. A significant myopic shift in refraction after laser capsulotomy was noted in the gravel appearance group compared to the milky appearance group (p = 0.027). No patient developed complications or needed further treatment for CBS during the median follow-up of 14.5 months (range 1–84 months).

Conclusion:

High-resolution anterior segment OCT is useful for analyzing patients with late CBS. Our study implies that the two types of CBS presentation indicate different causes of late CBS formation, as well as distinct clinical presentation and postlaser capsulotomy refractive outcome. In addition, YAG laser capsulotomy is a safe late CBS treatment modality.
Dipeptidyl peptidase-4 inhibitors attenuates osteoporosis in patients with diabetes: A nationwide, retrospective, matched-cohort study in Taiwan
Authors: Chang Chia-Hao , Lu Chieh Hua , Chung Chi-Hsiang , Su Sheng-Chiang , Kuo Feng-Chih , Liu Jhih-Syuan , Li Peng-Fei , Huang Chia-Luen , Chen Kuan-Chan , Ho Li-Ju , Kuo Chih-Chun , Chang Chun-Yung , Lin Ming-Shiun , Liu Yi-Chen , Chu Nain-Feng , Lee Chien-Hsing , Hung Yi-Jen , Hsieh Po-Shiuan , Lin Fu-Huang , Hsieh Chang-Hsun , Chien Wu-Chien
Published: June 2022

Background:

Patients with diabetes have a relatively high risk of fracture due to osteoporosis. However, the risk of osteoporosis associated with the use of oral hypoglycemic drugs and dipeptidyl peptidase-4 inhibitor (DPP-4i) by patients with diabetes is unclear. This study aimed to explore the effect of DPP-4i on the risk of osteoporosis in Taiwanese patients with type 2 diabetes mellitus (T2DM).

Methods:

This study enrolled 6339 patients on DPP-4i (DPP-4i group) and 25 356 patients without DPP-4i (non-DPP-4i group). They were matched by 1:4 propensity score matching, using confounding variables including sex, age, comorbidities, medication, and index year. Cox proportional hazards analysis was used to compare hospitalization and mortality during an average follow-up period of 7 years.

Results:

The mean age of patients in the two groups was 66 years. Men were slightly higher in number (51.79%) than women. At the end of the follow-up period, 113 (0.36%) patients had osteoporosis, of which 15 (0.24%) were in the case group and 98 (0.39%) in the control group. The risk of all-cause osteoporosis was significantly lower in the DPP-4i group than in the non-DPP-4i group (adjusted hazard ratio [HR] 0.616; 95% confidence interval [CI] 0.358–0.961; p = 0.011). Kaplan–Meier analysis showed that the preventive effect on osteoporosis was positively correlated with the cumulative dose of DPP-4i (log-rank, p = 0.039) with the class effect.

Conclusion:

Compared with not using DPP-4i, the use of DPP-4i in Taiwanese T2DM patients was associated with a lower risk of osteoporosis due to the class effect, and the preventive effect was dose-dependent. However, larger prospective studies are needed to validate this finding and to explore the possible mechanism of the preventive effect of DPP-4i.
Associated Mortality Risk of Proton Pump Inhibitor Therapy for the Prevention of Stress Ulceration in Intensive Care Unit Patients
Authors: Reynolds Paul M. , Wells Lauren , Powell Marissa , MacLaren Robert
Published: June 2022

Goals:

The aim was to systematically evaluate risks and benefits of proton pump inhibitor (PPI) use for stress ulcer prophylaxis in the critically ill patient.

Background:

Whether PPIs increase mortality in the critically ill patient remains controversial.

Study:

Systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort studies with trial sequential analysis, Bayesian sensitivity analysis, and fragility index analysis.

Results:

A total of 31 studies in 78,009 critically ill adults receiving PPIs versus any comparator were included. PPI use was associated with an increased mortality risk in all studies [19.6% PPI vs. 17.5% comparator; RR: 1.10; 95% confidence interval (CI): 1.02-1.20; P=0.01], in the subgroup of RCTs (19.4% vs. 18.7%; RR: 1.05; 95% CI: 1.0-1.09, P=0.04), but not cohort studies (19.9% vs. 16.7%; RR: 1.12; 95% CI: 0.98-1.28, P=0.09). Results were maintained with a Bayesian sensitivity analysis (RR: 1.13; 95% credible interval: 1.035-1.227) and a fragility index analysis, but not sequential analysis (P=0.16). RCTs with a higher baseline severity of illness revealed the greatest mortality risk with PPI use (32.1% PPI vs. 29.4% comparator; RR: 1.09; 95% CI: 1.04-1.14; P<0.001). PPI use reduced clinically important bleeding in RCTs (1.4% PPI vs. 2.1% comparator; RR: 0.67; 95% CI: 0.5-0.9; P=0.009) but increased bleeding in cohort studies (2.7% PPI vs. 1.2% comparator; RR: 2.05; 95% CI: 1.2-3.52; P=0.009). PPI use was not associated with a lower incidence of clinically important bleeding when compared with histamine-2 receptor antagonists (1.3% vs. 1.9%; RR: 0.59; 95% CI: 0.28-1.25, P=0.09).

Conclusions:

This meta-analysis demonstrated an association between PPI use and an increased risk of mortality.
Relevance of Excessive Air Swallowing in GERD Patients With Concomitant Functional Dyspepsia and Poor Response to PPI Therapy
Authors: Ribolsi Mentore , Savarino Edoardo , Frazzoni Marzio , Cicala Michele
Published: June 2022

Goals:

The present study was aimed at evaluating the possible role of air swallowing in the association between gastroesophageal reflux disease (GERD) symptoms and concomitant functional dyspepsia (FD) and their role in GERD symptom persistence despite proton pump inhibitor (PPI) therapy.

Background:

It has been shown that individuals with excessive air swallowing experience FD. It has been also demonstrated that a consistent group of GERD patients not responding to PPI therapy swallow more air during mealtime and also have more mixed refluxes.

Materials and Methods:

Multichannel intraluminal impedance-pH tracings from consecutive patients were retrospectively evaluated. A validated structured questionnaire was used to evaluate GERD and concomitant FD symptoms. All patients were treated, within the previous year, with at least 8 weeks of standard-dose PPI therapy.

Results:

A total of 35 patients with conclusive GERD, 35 patients with reflux hypersensitivity, and 35 with functional heartburn were studied. A direct relationship was observed between the number of air swallows and of mixed refluxes (R=0.64). At receiver operating characteristic curve analysis, air swallows and mixed refluxes were significantly associated to the presence of FD and PPI refractoriness. An air swallow cutoff of 107 episodes/24 hours was identified to discriminate patients with and without FD (sensitivity: 87%, specificity: 82.8%). A mixed reflux cutoff of 34 episodes/24 hours was identified to discriminate PPI responders from nonresponders (sensitivity: 84.8%, specificity: 69%). At multivariate analysis, an abnormal number of air swallows and of mixed refluxes were significantly associated to FD and PPI refractoriness.

Conclusion:

Our study highlights the relevant role of excessive air swallowing in eliciting both dyspepsia and refractoriness of typical GERD symptoms to PPI therapy.
Physician and Parent Perceptions on Plant-Based Beverages as Substitutes for Cow’s Milk: A Single City Survey
Authors: Fifi Amanda C. , Pagan Dianne N. , Chakraborty Partha , Mahajan Neha , Axelrod Cara , Bayes Liz Y. , Katz Daphna T.
Published: June 2022

This study assessed physician and parent perceptions regarding plant-based beverage consumption in children. We surveyed 128 physicians and 215 parents of patients at University of Miami and Jackson Memorial Hospital. Among physicians, 52% recommended plant-based beverages, typically soy (33%), for cow’s milk allergy (32%). Only 40% of physicians knew the typical protein content of plant-based beverages compared to cow’s milk. Most physicians (54%) did not discuss potential health risks of plant-based beverages with patients. Among parents, 48% had children <2 years old, and 22% purchased a plant-based beverage, most commonly almond beverage (39%), due to perceived health benefits (54%). In total, 85% of parents believed that plant-based beverages are nutritionally superior or equivalent to cow’s milk. Most parents (52%) depended on physicians for information on plant-based beverages. Overall, less than one third of physicians and parents believed that plant-based beverages should be called milk. There is a lack of knowledge among physicians and parents regarding plant-based beverage use as a dairy substitute in children. Despite parents relying on physicians for health information, physicians are not routinely counseling parents. Removing the label “milk” from plant-based beverages may improve consumer awareness of their nutritional differences and circumvent potential associated health risks in children.