bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycation-induced age-related illnesses, antiglycation and drug delivery strategies
Authors: Abdelkader Hamdy , Mustafa Wesam W , Alqahtani Ali M , Alsharani Sultan , Al Fatease Adel , Alany Raid G
Published: August 2022

Objectives

Ageing is a major cause of multiple age-related diseases. Several mechanisms have been reported to contribute to these abnormalities including glycation, oxidative stress, the polyol pathway and osmotic stress. Glycation, unlike glycosylation, is an irregular biochemical reaction to the formation of active advanced glycation end-products (AGEs), which are considered to be one of the causes of these chronic diseases. This study provides a recent and comprehensive review on the possible causes, mechanisms, types, analytical techniques, diseases and treatments of the toxic glycation end products.

Key findings

Several mechanisms have been found to play a role in generating hyperglycaemia-induced oxidative stress including an increase in the levels of reactive oxygen species (ROS), increase in the levels of AGEs, binding of AGEs and their receptors (RAGE) and the polyol pathway and thus have been investigated as promising novel targets.

This review focuses on the key mechanisms attributed to cumulative increases of glycation and pathological RAGE expression as a significant cause of multiple age-related diseases, and reporting on different aspects of antiglycation therapy as a novel approach to managing/treating age-related diseases. Additionally, historical, current and possible future antiglycation approaches will be presented focussing on novel drug delivery methods.
The access to CETA quotas: Extending CGE models with a market for quota licenses
Authors: Döbeling Tatjana
Published: August 2022

We analyze the market dynamics that are caused by tariff-rate quotas, particularly the effects of quota license allocation between heterogeneous commodities at the tariff line level. The allocation is endogenously modeled with a mixed complementarity problem approach for the case of the Comprehensive Economic and Trade Agreement between Canada and the European Union. The model results are compared both with alternative models that resemble pre-existing approaches and with the real trade figures that have been collected since the trade agreement's implementation. Our analysis shows a bias toward more expensive commodities if the shadow value of a quota license manifests in a secondary license market. The same quota can thereby be binding to some commodities but not so for others. This feature of quotas can be crucial for policymakers who are concerned about price effects or who want to understand the effects of lumping together commodities of different quality in one quota.
Acceptability of a brief fatigue intervention for inflammatory arthritis: a qualitative process evaluation
Authors: Berry Alice , Bridgewater Susan , Abbott Bryan , Adams Jo , Dures Emma
Published: August 2022

Objectives

We developed a brief cognitive behavioural, one-to-one intervention to reduce fatigue impact for patients with inflammatory arthritis. This qualitative process evaluation explored intervention acceptability and potential refinements from the perspective of patients who attended sessions and rheumatology health professionals (RHPs) who delivered the intervention.

Methods

Interviews were conducted with patients and RHPs from five National Health Service (NHS) sites. Data were analysed using inductive thematic analysis.

Results

Twenty-two patients and 11 RHPs participated.

Patient themes

Collaborative, non-judgemental consultations: patients valued having space to reflect, where their fatigue was validated. Relevant content, but not ground-breaking: patients appreciated the opportunity to tailor content to individual priorities. Daily diaries were useful to visualize fatigue. Self-awareness: patients reported increased acceptance, sense of control, and confidence to manage fatigue. Degrees of openness to change: sessions prompted patients to engage in behaviour change. For some, complicated lives made it difficult to plan for change.

RHP themes

Engagement with intervention: RHPs liked training face to face, and sessions were more enjoyable with experience of delivery. Research vs clinical practice: RHPs expressed concern about fitting sessions into NHS clinic appointments. It was difficult to offer follow-up sessions within 2 weeks. Collaborating with patients: RHPs reported that patients engaged with the tools and strategies. Some RHPs followed the manual in a linear way, whereas others used it flexibly.

Conclusion

There is potential for this brief fatigue intervention to benefit patients. Future research will focus on flexibility to fit with local services and creating educational resources to use in a range of contexts.
Overexpression of the FERONIA receptor kinase MdMRLK2 confers apple drought tolerance by regulating energy metabolism and free amino acids production
Authors: Jing Yuanyuan , Liu Changhai , Liu Bingbing , Pei Tingting , Zhan Minghui , Li Chunrong , Wang Duanni , Li Pengmin , Ma Fengwang
Published: August 2022

Drought is a major abiotic stress limiting the growth and production of apple trees worldwide. The receptor-like kinase FERONIA is involved in plant growth, development and stress responses; however, the function of FERONIA in apple under drought stress remains unclear. Here, the FERONIA receptor kinase gene MdMRLK2 from apple (Malus domestica) was shown to encode a plasma membrane-localized transmembrane protein and was significantly induced by abscisic acid and drought treatments. 35S::MdMRLK2 apple plants showed less photosystem damage and higher photosynthetic rates compared with wild-type (WT) plants, after withholding water for 7 days. 35S::MdMRLK2 apple plants also had enhanced energy levels, activated caspase activity and more free amino acids, than the WT, under drought conditions. By performing yeast two-hybrid screening, glyceraldehyde-3-phosphate dehydrogenase and MdCYS4, a member of cystatin, were identified as MdMRLK2 interaction partners. Moreover, under drought conditions, the 35S::MdMRLK2 apple plants were characterized by higher abscisic acid (ABA) content. Overall, these findings demonstrated that MdMRLK2 regulates apple drought tolerance, probably via regulating levels of energetic matters, free amino acids and ABA.
Sources of Bacterial Leaf Streak Resistance Identified in a Diverse Collection of Barley Germplasm
Authors: Ritzinger Mitchell G. , Smith Kevin P. , Case Austin J. , Wodarek Joseph R. , Dill-Macky Ruth , Curland Rebecca D. , Steffenson Brian J.
Published: August 2022

Bacterial leaf streak (BLS) is a sporadic yet damaging disease of cereals that is growing in importance across the Upper Midwest production region. In barley (Hordeum vulgare ssp. vulgare), this disease is caused primarily by the bacterium Xanthomonas translucens pv. translucens. Accessions resistant to BLS have been reported in past studies, but few have been rigorously validated in the field. To identify accessions carrying diverse resistance alleles to BLS, a largescale germplasm screening study was undertaken against strain CIX95 of X. translucens pv. translucens in St. Paul and Crookston, Minnesota, in 2020 and 2021. The germplasm screened was diverse and included adapted breeding lines from two improvement programs, two landrace panels (one global and one from Ethiopia/Eritrea), introgression lines from wild barley (H. vulgare ssp. spontaneum) in the genetic background of barley cultivar ‘Rasmusson’, and an assemblage of accessions previously reported to carry BLS resistance. Of the 2,094 accessions evaluated in this study, 32 (1.5%) exhibited a consistently high level of resistance across locations and years and had heading dates similar to standard cultivars grown in the region. Accessions resistant to BLS were identified from all germplasm panels tested, providing genetically diverse sources for barley improvement programs focused on breeding for resistance to this important bacterial disease.
Guided Growth for Varus Deformity Following Early Tibial Osteotomy in Infantile Tibia Vara—A Multi-Center Study
Authors: Walker Janet L. , Scott Allison C. , Stephenson Lindsay P. , Westberry David E. , Lerman Joel A. , Ackman Jeffery D. , Nossov Sarah B. , Franklin Corinna C.
Published: August 2022

Background:

Despite early osteotomy, many patients with infantile tibia vara (ITV) have persistent or recurrent varus deformity and disordered growth at the medial proximal tibial physis. Our hypothesis was that lateral tibial tension band plating (LTTBP) could guide correction.

Methods:

A retrospective review at 6 centers of 15 patients (16 extremities) was performed of LTTBP for varus deformity following early osteotomy in ITV, diagnosed≤4years of age. Correction of deformity parameters on digital standing anteroposterior lower extremity radiographs determined outcome.

Results:

Twenty-two LTTBP procedures were performed at mean age of 7.5 years, including 4 revisions for implant failure and 2 reimplantations for recurrence. Single event LLTBP, improved the medial proximal tibial angle with a mean change of 13.4 degrees (0.39 degrees/month). Eleven limbs had preoperative mechanical lateral distal femoral angle (mLDFA)>90 degrees. While n degree femoral procedures were performed, at study end, 11 femurs had mechanical lateral distal femoral angle≤90°. Pretreatment, 13 extremities had mechanical axis zone (MAZone) III varus (81%) and 3 had MAZone II varus (19%). LTTBP’s were able to initially correct 13 limbs to MAZone I or valgus but 4 limbs rebounded to MAZone II varus after implant removal. Final limb alignment, after all surgeries and rebound, included 9 in MAZone I, 5 in MAZone II varus and 2 in MAZone III varus. Average follow-up was 3.0 years at mean 10.7 years of age. Fifteen procedures resulted in improvement in MAZone and 7 had no change. On average, those that improved were younger (7.3 vs. 8.0 y), weighed less (45.5 kg with body mass index 26.5 kg/m2 vs. 67.8 kg and body mass index 35.7 kg/m2), had lower mechanical axis deviation (37.1 mm vs. 43.9 mm), lower medial physeal slope (61.7 vs. 68.7 degrees) and had a higher percentage of open triradiate phases (87 vs. 57%).

Conclusions:

LTTBP for residual varus, after initial osteotomy in ITV, resulted in 81% of limbs initially achieving MAZone I or valgus with implant failure revisions and femoral remodeling. Rebound after implant removal reduced the corrected rate to 56%. Ninety-four percent avoided osteotomy during the study period.

Level of Evidence:

IV
A Quasi-experimental of a Virtual Reality Content Intervention for Level of Comfort of Indonesian Cancer Patients
Authors: Jadmiko Arief Wahyudi , Kristina Tri Nur , Sujianto Untung , Prajoko Yan Wisnu , Dwiantoro Luky , Widodo Aris Puji
Published: August 2022

This study aims to determine the effect of virtual reality content on the comfort level of cancer patients. This study used a quasi-experimental non-equivalent control group design and was conducted on 60 cancer patients. The intervention uses the virtual reality content “My Comfortable Environment,” which was developed based on Kolcaba's comfort theory. Comfort level was measured using the Shortened General Comfort Questionnaire. The Wilcoxon and Mann-Whitney U tests were used to determine the differences before and after the intervention within the group and between the study groups. There was a significant mean difference between pre-test and post-test in the intervention group with P < .000, Z = −4.785, and in the control group with P < .041, Z = −2.032. These results indicate that interventions with virtual reality content and guided imagery both affect the comfort level of cancer patients. However, if the test was conducted between groups, there was a significant difference between the intervention group and the control group with a P value of <.000. These results indicate that the virtual reality content intervention can significantly increase the level of patient comfort through modifying various aspects of patient comfort, especially environmental aspects.
Sodium Ferulate Inhibits Rat Cardiomyocyte Hypertrophy Induced by Angiotensin II Through Enhancement of Endothelial Nitric Oxide Synthase/Nitric Oxide/Cyclic Guanosine Monophosphate Signaling Pathway
Authors: Luo Min , Lin Hui-Cai , Wen Zhao-Qin , Chen Pan-Pan , Shi Wan-Lan , Li Ying-Ying , Gao Yang , Xu Shang-Fu , Xu Rui-Xia , Gong Qi-Hai , Deng Jiang
Published: August 2022

Sodium ferulate (SF) is the sodium salt of ferulic acid, which is one of the effective components of Angelica sinensis and Lignsticum chuanxiong, and plays an important role in protecting the cardiovascular system. In this study, myocardial hypertrophy was induced by angiotensin II 0.1 μmol/L in neonatal Sprague–Dawley rat ventricular myocytes. Nine groups were designed, that is, normal, normal administration, model, L-arginine (L-arg 1000 μmol/L), SF (50, 100, 200 μmol/L) group, and NG-nitro-L-arg-methyl ester 1500 μmol/L combined with SF 200 μmol/L or L-arg 1000 μmol/L group, respectively. Cardiomyocyte hypertrophy was confirmed by observing histological changes and measurements of cell diameter, protein content and atrial natriuretic factor, and β-myosin heavy chain levels of the cells. Notably, SF could inhibit significantly myocardial hypertrophy of neonatal rat cardiomyocytes in a concentration-dependent manner without producing cytotoxicity, and the levels of nitric oxide, NO synthase (NOS), endothelial NOS, and cyclic guanosine monophosphate were increased, but the level of cyclic adenosine monophosphate was decreased in cardiomyocytes. Simultaneously, levels of protein kinase C beta, Raf-1, and extracellular regulated protein kinase 1/2 (ERK1/2) were downregulated, whereas levels of mitogen-activated protein kinase phosphatase-1 were significantly upregulated. All the beneficial effects of SF were blunted by NG-nitro-L-arg-methyl ester. Overall, these findings reveal that SF can inhibit angiotensin II-induced myocardial hypertrophy of neonatal rat cardiomyocytes, which is closely related to activation of endothelial NOS/NO/cyclic guanosine monophosphate, and inhibition of protein kinase C and mitogen-activated protein kinase signaling pathways.
IV Sodium Ferric Gluconate Complex in Patients With Iron Deficiency Hospitalized due to Acute Heart Failure—Investigator Initiated, Randomized Controlled Trial
Authors: Marcusohn Erez , Borreda Itay , Hellman Yaron , Habib Manhal , Bahouth Fadel , Epstein Danny , Zukermann Robert
Published: August 2022

Patients with heart failure (HF) with iron deficiency (ID) have worse New York Heart Association class and are at a higher risk of recurrent hospitalizations. Intravenous (IV) iron has been shown to improve exercise ability and reduce hospitalizations. IV sodium ferric gluconate complex (SFGC) has been found to be safe and affordable but has not been studied in this population in a randomized trial. This was a prospective, single-blind, investigator-initiated, randomized controlled trial. Patients admitted for acute heart failure with ID were randomly assigned 1:1 to receive IV SFGC on top of optimal medical treatment. The primary outcome was the change in the 6-minute walk test (6MWT) from baseline to 3 and 6 months. Between September 2019 and May 2021, 34 patients were randomized. 19 patients (55%) were randomized to the treatment arm receiving 125 mg of IV SFGC per day for 3–5 days. COVID-19 was a major barrier to the implementation of the study follow-up protocol, which caused the study to end early. Both groups of patients had similar clinical characteristics, comorbidities, median left ventricular ejection fraction, and rate of death and readmissions due to HF. A higher level of NT-proBNP was observed in patients treated with IV iron (7902 pg/mL vs. 3158, P = 0.04). There was no difference in 6MWT change between groups at 3 months (improvement of 21.6 vs. 24.1 meters) or 6 months (−5 meters vs. 46 meters). In conclusion, IV SFGC–treated patients had a comparable 6-minute walk at 3 and 6 months despite suffering from more severe HF with higher baseline NT-proBNP (NCT04063033).
Dual Antiplatelet Therapy After Drug-Eluting Stents Implantation in East Asians: A Network Meta-Analysis of Randomized Controlled Trials
Authors: Zhong Peng-Yu , Shang Yao-Sheng , Bai Nan , Ma Ying , Niu Ying , Wang Zhi-Lu
Published: August 2022

Dual antiplatelet therapy (DAPT) is essential to prevent the risk of ischemia events, but it is difficult to avoid concurrent bleeding events. East Asians are associated with a higher tendency of bleeding than Caucasians, which may affect the DAPT duration. Therefore, this network meta-analysis to explore optimum DAPT duration for East Asians. The related randomized controlled trials that compared the different DAPT duration in East Asian patients were included by searching PubMed, EMBASE, and Cochrane Library database. The outcomes included myocardial infarction, stent thrombosis, all-cause death, stroke, and major bleeding. In addition, net adverse cardiac and cardiovascular events was defined as a composite outcome in this study. We calculated the odds ratio (OR) and 95% confidence intervals for end point events by the fixed effects model in the Bayesian’s network frame. We included a total of 12 randomized controlled trials with 30,640 patients. Compared with 12-month DAPT, 1- to 3-month DAPT is effective in myocardial infarction (OR 0.72, 0.46–1.08), stents thrombosis (OR 1.27, 0.59–2.84), all-cause death (OR 0.91, 0.65–1.28), and stroke (OR 0.89, 0.57–1.39). The 1- to 3-month DAPT was associated with a lower risk of major bleeding compared with 12-month DAPT (OR 0.55, 0.4–0.76), 6-month DAPT (OR 0.54, 0.31–0.94), and >12-month DAPT (OR 0.43, 0.28–0.65). In addition, more than 12 months of DAPT did not reduce the incidence of myocardial infarction (OR 0.75, 0.51–1.11) and increased the risk of major bleeding (OR 1.28, 0.88–1.87) compared with 12-month DAPT. The 1- to 3-month DAPT was more secure and effective than the other 3 DAPT strategies. Although East Asians have a higher risk of bleeding, more than 12 months of DAPT does not increase this incidence of major bleeding.
Is the 5-hydroxytryptamine 7 Receptor Constitutively Active in the Vasculature? A Study in Veins/Vein
Authors: Watts Stephanie W. , Flood Emma D. , Thompson Janice M.
Published: August 2022

The 5-hydroxytryptamine 7 (5-HT7) receptor is reported to have considerable constitutive activity when transfected into cells. Constitutive activity—receptor activity in the absence of known agonist—is important for understanding the contributions of a receptor to (patho)physiology. We test the hypothesis that the 5-HT7 receptor possesses constitutive activity in a physiological situation. Isolated veins from male and female Sprague Dawley rats were used as models for measuring isometric force; the abdominal vena cava possesses a functional 5-HT7 receptor that mediates relaxation, whereas the small mesenteric vein does not. Compounds reported to act as inverse agonists were investigated for their ability to cause contraction (moving a constitutively active relaxant receptor to an inactive state, removing relaxation). Compared with a vehicle control, clozapine, risperidone, ketanserin, and SB269970 caused no contraction in the isolated male abdominal vena cava. By contrast, methiothepin caused a concentration-dependent contraction of the male but not female abdominal vena cava, although with low potency (−log EC50 [M] = 5.50 ± 0.45) and efficacy (∼12% of contraction to endothelin-1). Methiothepin-induced contraction was not reduced by the 5-HT7 receptor antagonist (SB269970, 1 μM, not active in the vena cava). These same compounds showed little to no effect in the isolated mesenteric vein. We conclude that the 5-HT7 receptor in the isolated veins of the Sprague Dawley rat does not possess constitutive activity. We raise the question of the physiological relevance of constitutive activity of this receptor important to such diverse physiological functions as sleep, circadian rhythm, temperature, and blood pressure regulation.
Reproducible Quantification of Unbound Fractions of Four Beta-Lactam Antibiotics: Ultrafiltration Versus Microdialysis of Spiked Healthy Donor Plasma
Authors: Beijer Gustaf , Clarin Leona , Östervall Jennie , Barclay Victoria , Eliasson Erik
Published: August 2022

Background:

Ultrafiltration (UF) is a conventional method for isolating the protein-unbound plasma fractions of therapeutic drugs. However, the ideal UF conditions for specific compounds remain largely unexplored. By comparing UF-derived unbound concentrations with the corresponding results obtained using a reference method, the authors sought to identify appropriate UF conditions for cefotaxime, cloxacillin, flucloxacillin, and piperacillin.

Methods:

In vitro microdialysis (MD) with a no-net-flux approach was used as a reference method for plasma protein separation, for which UF performance was assessed. Four levels of relative centrifugal force (2500–11,290g) and 2 levels of temperature (37 vs. 22°C) during 10 minutes of UF centrifugation were evaluated. Ultrafiltrates and reference microdialysates were analyzed using liquid chromatography-tandem mass spectrometry to obtain unbound concentrations. After identifying the appropriate UF conditions in the spiked plasma samples, exploratory analyses of clinical samples (n = 10 per analyte) were performed.

Results:

Of the evaluated UF alternatives, the best overall agreement with the MD-derived reference concentrations was obtained with 11,290 g UF performed at 22°C. For cloxacillin specifically, 37°C UF yielded better agreement than 22°C UF at 11,290 g. Clinical sample analyses indicated minimal differences between 22°C and 37°C at 11,290 g UF for cefotaxime and piperacillin. However, consistently lower levels of unbound cloxacillin (median: −23%, IQR: −19% to −24%) and flucloxacillin (median: −27%, IQR: −21 to −34%) were observed after UF at 22°C versus 37°C.

Conclusions:

For the evaluated UF device, 10 minutes of 11,290 g UF at 22°C is appropriate for flucloxacillin, cefotaxime, and piperacillin, and can arguably be justified for cloxacillin as well for laboratory practice purposes. Maintenance of 37°C during high-centrifugal UF may lead to overestimation, particularly for unbound flucloxacillin.
Differences in Practitioner Experience, Practice Type, and Profession in Attitudes Toward Growing Contact Lens Practice
Authors: Thite Nilesh , Desiato Alfredo , Shinde Lakshmi , Wolffsohm James S , Naroo Shehzad A. , Santodomingo Rubido Jacinto , Cho Pauline , Jones Debbie , Villa-Collar Cesar , Carrillo Guillermo , Chan Osbert , Wang Haiying , Iomdina Elena , Tarutta Elena , Proskurina Olga , Fan Chi Shing , Zeri Fabrizio , Bakkar May M. , Barodawala Fakhruddin , Dabral Neeraj , Lafosse Edouard , Lee Cheni , Nichols Jason , Chan Jack , Park Kyounghee , Nair Vishakh , van der Worp Eef , Vankudre Gopi , Maseedupally Vinod , Bhattarai Yashaswee , Nagzarkar Dimple , Brauer Peter , Gil-Cazorla Raquel
Published: August 2022

Objective:

To investigate eye care practitioners' attitudes and perceptions toward potential interventions that can enhance contact lens (CL) practice across the world, and how this is influenced by their practice setting.

Methods:

A self-administered, anonymized survey was constructed in English and then forward and backward translated into six more languages. The survey was distributed online via social media platforms and mailing lists involving reputed international professional bodies.

Results:

In total, 2,222 responses from 27 countries with sufficient responses were analyzed (53% females, median age- 37 years). Most of the respondents were optometrists (81.9%) and 47.6% were from stand-alone/independent practices. Median working experience in CL prescribing was 11.0 years (IQR: 18.0, 4–22 years). Over two-third of them declared themselves to be very hopeful (22.9%) or hopeful (45.1%) about the future of their CL practice. Among the potential interventions proposed, continuous update of knowledge and skills and competently managing CL-related complications were rated the most important (median score: 9/10 for each). Practitioners working in national/regional retail chains expressed higher proactivity in recommending CLs (9/10) than those in local chains, hospitals, and universities (for all 8/10, P<0.05). National differences were also identified in eye care practitioner attitudes and perceptions (P<0.05).

Conclusions:

The study provided important information to delineate a variety of elements characterizing CL practice across the world. These insights can serve as a basis to design strategies at national and international levels.
Tear Exchange, Intraocular Pressure, and Wear Characteristics of Quadrant-specific Versus Spherical Haptic Scleral Lenses
Authors: Nau Cherie B. , Schornack Muriel M. , McLaren Jay W. , Hochwald Alexander P. , Carrasquillo Karen G.
Published: August 2022

Objectives:

To compare scleral lenses (SLs) with a quadrant-specific (study lens) or a spherical (habitual lens) landing zone in a crossover study.

Methods:

Seven participants (eight eyes) wore each of two lenses for 2 weeks before measurements. We measured visual acuity, contrast sensitivity, intraocular pressure (IOP), fluid reservoir clearance, corneal thickness, tear exchange, and lens experience. Variables were compared between lenses and before and after 2 hr of wear.

Results:

The visual acuity was not different between the study lens, 0.12 logarithm of the minimum angle of resolution (logMAR), and habitual lens, 0.18 logMAR (median, P = 1.0). Contrast sensitivity was 1.3% under the study lens and 1.6% under the habitual lens (P = 0.94). IOP did not change after 2 hr of wear for either lens (study lens, P = 0.33 and habitual lens, P = 0.74), and corneal thickness did not change during wear of either lens (P = 0.44). The fluorescein concentration under the study lens did not change after 2 hr (99% of initial concentration; P = 0.84) but decreased to 46% of initial concentration under the habitual lens (P = 0.008). Lens comfort was slightly better with the study lens (5.0 vs. 4.0, respectively; P = 0.05).

Conclusions:

SLs with spherical or quadrant-specific landing zones provide good vision and do not affect IOP or corneal thickness. However, tear exchange is greater under spherical lenses than under quadrant-specific lenses. The quadrant-specific lens provides greater patient comfort.
Mirror peripheral neuropathy and unilateral chronic neuropathic pain: insights from asymmetric neurological patterns in leprosy
Authors: Raicher Irina , Zandonai Alexandra P. , Anghinah Isadora W. , Frassetto Mariana , Stump Patrick R. N. A. G. , Trindade Maria A. B. , Harnik Simone , Oliveira Rodrigo A. , Macarenco Ricardo S. S. , Doppler Kathrin , Üçeyler Nurcan , Mello Evandro S. , Sommer Claudia , Teixeira Manoel J. , Galhardoni Ricardo , de Andrade Daniel C.
Published: August 2022

Leprosy-related multiple mononeuropathy offers a pattern of impairment where neuropathy with and without neuropathic pain (NeP) are present in the same individual, thus allowing to investigate peripheral sensory and innervation in both conditions. This cross-sectional study collected data on clinical and neurological examination, pain assessment questionnaires, quantitative sensory test, and intraepidermal nerve fiber density of patients with leprosy and divided the cohort into 2 groups: with NeP (P+) and without NeP (P−). Furthermore, we assessed mirror body areas in the same NeP individuals with bilateral neuropathy also presenting unilateral NeP. Pain-free patients having unilateral neuropathy were controls. A total of 37 P+ and 22 P− patients were evaluated. Limb areas with NeP had signs of C-fiber dysfunction and hyperesthesia on quantitative sensory testing compared with limb areas having neuropathy without NeP. Skin denervation was found in all patients with leprosy. Comparisons of limbs with and without neuropathy and with and without NeP revealed that higher heat pain thresholds (HPTs) were associated with neuropathic pain areas, whereas less altered HPT was correlated with higher fiber density. Furthermore, a relationship was found between time of leprosy treatment termination and more intense neuropathy, expressed by HPT increasing 0.03°C each month. As expected, interindividual comparisons failed to show differences in intraepidermal nerve fiber density and subepidermal plexus areas between P+ and P− patients (P = 0.2980, P = 0.9044; respectively). Higher HPT and lower mechanical detection threshold were related to NeP. This study pointed out the relevance of intraindividual comparisons including mirror areas when assessing local changes in peripheral NeP.
Slight High-Frequency Hearing Loss, Effect of COVID-19 or Hydroxychloroquine Usage?
Authors: Rahimi Vida , Rouhbakhsh Nematollah , Manshadi Seyed Ali Dehghan
Published: August 2022

Background and Objectives

Concerns about ototoxic and vestibulotoxic effects have been raised with the use of antiviruses in the treatment of COVID-19. This study aimed to determine the effect of hydroxychloroquine (HCQ) and examine the auditory system and its associated auditory and vestibular symptoms in patients with COVID-19.

Study Design

Prospective study.

Patients

Thirty patients with a history of HCQ (HCQ+) and 30 patients without drug use (HCQ−), and 30 healthy adults as the control group participated.

Main Outcome Measure(s)

Audiological assessments and evaluation of audio-vestibular symptoms. Evaluations were also repeated 1 month later.

Results

Both HCQ+ and HCQ− groups showed poor pure-tone audiometry (PTA) thresholds and decreased transient evoked otoacoustic emission amplitudes at high frequencies in comparison to the healthy group. Despite the lack of significant differences in PTA between the two groups of patients, the differences in transient evoked otoacoustic emission amplitudes were significant. PTA thresholds and otoacoustic emission showed improvement after 1 month. Dizziness was the most common symptom that was reduced after 1 month.

Conclusion

Slight hearing loss was seen in patients with COVID-19 with or without HCQ. Also, hearing thresholds in the HCQ+ group did not show a significant difference compared with the HCQ− group. Nevertheless, it seems that more damage is done to the hair cells of patients with HCQ intake than in other patients. Hence, the ototoxicity effect of high doses of HCQ use in the COVID-19 patients should be considered. A relative improvement in the hearing was seen over time in both patient groups.
Image-Guided Cochlear Implant Programming: A Systematic Review and Meta-analysis
Authors: Yang Alex W. , Lee Katie F. , Noller Michael , Watson Nora , Pillion Elicia M. , Riley Charles A. , Tolisano Anthony M.
Published: August 2022

Objective

To review studies evaluating clinically implemented image-guided cochlear implant programing (IGCIP) and to determine its effect on cochlear implant (CI) performance.

Data Sources

PubMed, EMBASE, and Google Scholar were searched for English language publications from inception to August 1, 2021.

Study Selection

Included studies prospectively compared intraindividual CI performance between an image-guided experimental map and a patient's preferred traditional map. Non-English studies, cadaveric studies, and studies where imaging did not directly inform programming were excluded.

Data Extraction

Seven studies were identified for review, and five reported comparable components of audiological testing and follow-up times appropriate for meta-analysis. Demographic, speech, spectral modulation, pitch accuracy, and quality-of-life survey data were collected. Aggregate data were used when individual data were unavailable.

Data Synthesis

Audiological test outcomes were evaluated as standardized mean change (95% confidence interval) using random-effects meta-analysis with raw score standardization. Improvements in speech and quality-of-life measures using the IGCIP map demonstrated nominal effect sizes: consonant–nucleus–consonant words, 0.15 (−0.12 to 0.42); AzBio quiet, 0.09 (−0.05 to 0.22); AzBio +10 dB signal-noise ratio, 0.14 (−0.01 to 0.30); Bamford–Kowel–Bench sentence in noise, −0.11 (−0.35 to 0.12); Abbreviated Profile of Hearing Aid Benefit, −0.14 (−0.28 to 0.00); and Speech Spatial and Qualities of Hearing Scale, 0.13 (−0.02 to 0.28). Nevertheless, 79% of patients allowed to keep their IGCIP map opted for continued use after the investigational period.

Conclusion

IGCIP has potential to precisely guide CI programming. Nominal effect sizes for objective outcome measures fail to reflect subjective benefits fully given discordance with the percentage of patients who prefer to maintain their IGCIP map.
Reassessing the Need for Preoperative Transfusions in Sickle Cell Disease Patients With an Elevated Baseline Hemoglobin—A Retrospective Study
Authors: Yan Adam , Tole Soumitra , Bair Lissa , Wagner Amanda , Tang Ken , Kirby-Allen Melanie , Simpson Ewurabena , Williams Suzan
Published: August 2022

Background:

Current guidelines recommend a preoperative hemoglobin of 10.0 g/dL in patients with sickle cell disease [SCD], however, this threshold continues to be an area of controversy. Previous studies demonstrating the benefits of preoperative transfusions have largely not captured patients with elevated baseline hemoglobin, in part due to low hydroxyurea uptake and exclusion of nonhemoglobin SS SCD.

Materials and Methods:

We conducted a retrospective chart review of patients with SCD <18 years of age undergoing low and medium-risk procedures at 2 academic medical centers in Canada between 2007 and 2017. The primary objective was to study the association of preoperative transfusion on postoperative complications in patients with SCD with baseline hemoglobin between 9.0 and 10.0 g/dL. Multivariable logistic regression was used to estimate the adjusted effect of preoperative transfusion on the risk of developing postoperative complications.

Results:

In all, 159 procedures in patients with hemoglobin <9.0 g/dL [Hb<9.0] and 173 procedures in patients with hemoglobin between 9.0 and 10.0 g/dL [Hb9.0-10.0] were analyzed. In the absence of preoperative transfusion, Hb9.0-10.0 patients had lower overall complications [23% vs. 34%] compared with Hb<9.0 patients [OR 0.29, 95% CI 0.12-0.72, P=0.008]. In total, 75% of Hb<9.0 and 21% of Hb9.0-10.0 patients received a preoperative simple transfusion. Transfusion was associated with increased risk of postoperative complications in Hb9.0-10.0 [OR 3.02, 95% CI 1.26-7.23, P=0.013], but not Hb<9.0 patients [OR 0.64, 95% CI 0.28-1.45, P=0.30].

Conclusions:

Simple transfusion may not be warranted in Hb9.0-10.0 patients undergoing low-risk procedures. Prospective studies validating these findings are needed.
Factors Associated With Fertility Preservation in a Pediatric, Adolescent and Young Adult Population
Authors: Sax Megan R. , Pettengill Grace , Hasija Abhinav , Ferrara Brycen , Frias Olivia , Riazzi Abbey , Spitznagel Elizabeth , Burns Karen , Strine Andrew C. , Rios Julie Sroga
Published: August 2022

Objective:

To determine the patient characteristics associated with pursuing fertility preservation (FP) before gonadotoxic therapy in a pediatric, adolescent and young adult patient population.

Methods:

This is a retrospective cohort study of patient data at Cincinnati Children’s Hospital Medical Center. Demographics, clinical diagnoses, and treatment characteristics were compared between participants that selected FP versus those that declined. Variables were analyzed separately for males and females by logistic regression.

Results:

Patients with a hematologic cancer were less likely to be eligible for preservation: 53.9% of ineligible males, P<0.001, and 51.8% of ineligible females, P<0.0001. Among patients who were candidates for FP, those receiving high-risk therapy were more likely to elect for FP (65.3% males, P<0.0001, and 87.5% of females, P<0.0001). Pubertal males were more likely to undergo preservation than prepubertal males (70.5% vs. 29.5%, P<0.0001; however, this trend was not demonstrated among female patients. In both males and females, race, ethnicity, religion, primary language, and insurance status were not shown to be statistically significant factors in predicting utilization of FP.

Conclusion:

Risk of infertility, type of cancer, and developmental status influenced decisions on pursuing FP in pediatric, adolescent and young adult patients facing iatrogenic infertility.
Polo-like Kinase 4: the Variation During Therapy and its Relation to Treatment Response and Prognostic Risk Stratification in Childhood Acute Lymphoblastic Leukemia Patients
Authors: Xu Junfang , Zhao Liping
Published: August 2022

Polo-like kinase 4 (PLK4) plays an essential role in the tumorigenesis of some blood malignancies; consequently, we hypothesized that PLK4 might serve as a potential biomarker in childhood acute lymphoblastic leukemia (ALL) patients. Therefore, this study investigated the expression of PLK4 and its clinical relevance in childhood ALL patients. Bone marrow specimens were collected from 95 childhood ALL patients and 20 primary immune thrombocytopenia patients (as controls), and their PLK4 expression (reverse transcription-quantitative polymerase chain reaction) was measured after enrollment. Besides, the PLK4 expression in childhood ALL patients was also determined at day 15 after the initiation of induction therapy (D15). PLK4 was increased in childhood ALL patients compared with controls (2.830 (interquartile range (IQR): 1.890-3.660) versus 0.976 (IQR: 0.670-1.288), P≤0.001). PLK4 at diagnosis was elevated in T cell acute lymphoblastic leukemia patients than in B cell acute lymphoblastic leukemia patients (P=0.027). Besides, PLK4 at diagnosis was positively linked with the Chinese Medical Association risk stratification (P=0.016), but not with prednisone response (P=0.077) or bone marrow response (P=0.083). In addition, PLK4 was decreased at D15 after treatment compared with at diagnosis (P≤0.001). Interestingly, PLK4 at D15 (P=0.033) was elevated in T cell acute lymphoblastic leukemia patients than in B cell acute lymphoblastic leukemia patients. Furthermore, increased PLK4 at D15 was associated with poor prednisone response (P=0.018), poor bone marrow response (P=0.034), and increased the Chinese Medical Association risk stratification (P=0.015). In terms of prognosis, high PLK4 was associated with shorter event-free survival (P=0.020), whereas it was not related to the overall survival (P=0.135). In conclusion, PLK4 has the potential as a biomarker for treatment response and prognostic risk stratification of childhood ALL patients.
Human Immunodeficiency Virus Associated Plasmablastic Lymphoma Involving Bones and Peritoneum in a 4-Year-old Child
Authors: Ramanathan Subramaniam , Moulik Nirmalya Roy , Dhamne Chetan , Shah Sneha , Shet Tanuja , Narula Gaurav
Published: August 2022

In children with underlying Human Immunodeficiency virus infection and AIDS, hematolymphoid cancers, especially non-hodgkin lymphomas are common. Plasmablastic lymphoma is one such non-hodgkin lymphomas arising from the head and neck region (especially sinonasal) but extremely rare. We describe the clinical course in a 4-year-old boy who presented with a solitary bony swelling of the right knee joint, which on diagnostic work-up turned out to be plasmablastic lymphoma. With combination chemotherapy, intrathecal chemotherapy, and early institution ofHighly active anti-retroviral therapy, the child continues to be in remission.
Investigating the Impact of Moringa oleifera Supplemented to Kenyan Breastfeeding Mothers on Maternal and Infant Health: A Cluster Randomized Single-Blinded Controlled Pilot Trial Protocol
Authors: Mogaka Jerusha Nyabiage , Owuor Patrick Mbullo , Odhiambo Silvia , Waterman Carrie , McGuire Michelle K. , Fuchs George J. , Attia Suzanna L.
Published: August 2022

Background:

Undernutrition contributes to up to 45% of deaths globally in children <5 years, with an optimal time for intervention before 24 months of age. Breastmilk microbiome helps establish the infant intestinal microbiome and impacts infant intestinal and nutritional health. Inadequacies in breastmilk composition such as low vitamin A contribute to infant nutrient deficiencies. Changes in milk fatty acid composition (reduced saturated and increased unsaturated fatty acids) may reduce susceptibility to enteric infection and increase protective intestinal bacteria. Moringa oleifera leaves (moringa) provide high nutrient concentrations (including protein, iron, vitamin A) and increase milk production; this may enhance breastmilk quantity and quality and improve infant health.

Objective:

To investigate the role of moringa supplementation to improve maternal and infant nutritional and intestinal health via changes in maternal milk quantity and quality.

Methods:

Fifty mother-infant pairs exclusively breastfeeding will be enrolled in a single-blinded randomized controlled trial in Kombewa County Hospital and Chulaimbo SubCounty Hospital, Kisumu, Kenya.

Intervention:

Dietary Supplementation of 20 g of Moringa oleifera leaf powder divided twice daily in corn porridge consumed daily for 3 months while control comparator will receive porridge daily for 3 months.

Outcomes:

Change in infant growth and maternal milk output (primary); maternal and infant vitamin A and iron status, changes in infant and maternal intestinal health (secondary).

Participating Centers:

Pamoja Community Based Organization, Kombewa Sub-County Hospital, and Chulaimbo Sub-County Hospital.
Hyperparathyroidism Caused by Coexisting Parathyroid Hyperplasia and Unilateral Bifocal Parathyroid Carcinoma
Authors: Liu Wei , Huang Jian-Min , Guan Mei-Chao , Xie Peng
Published: August 2022

The coexistence of parathyroid hyperplasia and carcinoma is uncommon. Here we report findings of 99mTc-sestamibi SPECT/CT study in a case of unilateral bifocal parathyroid carcinoma coexisting with parathyroid hyperplasia in a 49-year-old man. The images showed 4 foci of elevated activity around the thyroid. Histopathology confirmed the 2 lesions of the left side as parathyroid hyperplasia and the other 2 lesions of the right side as parathyroid carcinoma.
Ethical Considerations Surrounding Surgeon Ownership of Ambulatory Surgery Centers
Authors: Xu Amy L , Jain Amit , Humbyrd Casey Jo
Published: August 2022

As surgical care continues to transition to an outpatient setting, ambulatory surgery centers (ASCs) present favorable options for physician investment. As of 2017, more than 90% of ASCs have at least some physician ownership, with 64% solely physician-owned. Yet, physician ownership creates an inherent conflict of interest known as dual agency, where clinicians have a personal financial stake in addition to their obligation towards patient well-being. Here, we assess the ethical considerations surrounding dual agency in the setting of ASCs through the lens of beneficence, nonmaleficence, autonomy, and justice. We further propose strategies for appropriate navigation of such situations, including disclosure of ownership status, instruction on unfamiliar techniques, and adherence to accepted clinical practice guidelines for materials selection and surgical indications.
Night Radiology Coverage for Trauma: Residents, Teleradiology, or Both?
Authors: Yeates Eric O , Grigorian Areg , Chinn Justine , Young Hayley , Colin Escobar Jessica , Glavis-Bloom Justin , Anavim Arash , Yaghmai Vahid , Nguyen Ninh T , Nahmias Jeffry ,   for the UCI Trauma Radiology Study Group
Published: August 2022

BACKGROUND:

Overnight radiology coverage for trauma patients is often addressed with a combination of on-call radiology residents (RR) and a teleradiology service; however, the accuracy of these 2 readers has not been studied for trauma. We aimed to compare the accuracy of RR versus teleradiologist interpretations of CT scans for trauma patients.

STUDY DESIGN:

A retrospective analysis (March 2019 through May 2020) of trauma patients presenting to a single American College of Surgeons Level I trauma center was performed. Patients whose CT scans were performed between 10pmto 8amwere included, because their scans were interpreted by both a RR and teleradiologist. Interpretations were compared with the final attending faculty radiologist’s interpretation and graded for accuracy based on the RADPEER scoring system. Discrepancies were characterized as traumatic injury or incidental findings and missed findings or overcalls. Turnaround time was also compared.

RESULTS:

A total of 1,053 patients and 8,226 interpretations were included. Compared with teleradiologists, RR had a lower discrepancy (7.7% vs 9.0%, p = 0.026) and major discrepancy rate (3.8% vs 5.2%, p = 0.003). Among major discrepancies, RR had a lower rate of traumatic injury discrepancies (3.2% vs 4.4%, p = 0.004) and missed findings (3.4% vs 5.1%, p < 0.001), but a higher rate of overcalls (0.5% vs 0.1%, p < 0.001) compared with teleradiologists. The mean turnaround time was shorter for RR (51.3 vs 78.8 minutes, p < 0.001). The combination of both RR and teleradiologist interpretations had a lower overall discrepancy rate than RR (5.0% vs 7.7%, p < 0.001).

CONCLUSIONS:

This study identified lower discrepancy rates and a faster turnaround time by RR compared with teleradiologists for trauma CT studies. The combination of both interpreters had an even lower discrepancy rate, suggesting this combination is optimal when an in-house attending radiologist is not available.