bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutritional importance of tryptophan for improving treatment in depression and diabetes
Authors: Haleem Darakhshan Jabeen
Published: August 2022

The importance of nutrients in our diet is becoming increasingly recognized. From the viewpoint of protein synthesis and other physiologic and metabolic functions, all amino acids are important, but some of these amino acids are not synthesized endogenously. This subset, called essential amino acids, comprise dietarily indispensable nutrients. Tryptophan, an essential amino acid, is the sole precursor of neuronal as well as peripheral serotonin (5-hydroxytryptamine). Its systemic or oral administration increases serotonin synthesis because tryptophan hydroxylase, the rate-limiting enzyme of 5-hydroxytryptamine biosynthesis, is physiologically unsaturated with its substrate. Central serotonin is implicated in a number of psychiatric illnesses, including depression, and in responses to stress. Acting peripherally, serotonin affects vasoconstriction, intestinal motility, control of T cell–mediated immunity, and liver and pancreatic functions. Depression and diabetes are 2 highly prevalent diseases that often coexist. There is evidence that occurrence of depression is 2–3 times higher in people with diabetes mellitus. A comorbid condition of diabetes and depression worsens the treatment and increases risk for death. Stress, known for its causal role in depression, can also enhance risk for diabetes. Stress-induced decreases in the circulating levels of tryptophan can impair brain and pancreatic serotonin-dependent functions to precipitate these diseases. The importance of tryptophan supplementation for improving therapeutic intervention in depression and diabetes is the focus of this article. A deficiency of this essential amino acid may enhance risk for depression as well as diabetes, and can also weaken treatment efficacy of medicinal compounds for treating these diseases. Guidelines for optimal levels of circulating tryptophan can help if supplements of this amino acid can improve treatment efficacy.
An overview of vitamins as epidrugs for colorectal cancer prevention
Authors: Boughanem Hatim , Kompella Pallavi , Tinahones Francisco J , Macias-Gonzalez Manuel
Published: August 2022

Gene expression altering epigenomic modifications such as DNA methylation, histone modification, and chromosome remodeling is crucial to regulating many biological processes. Several lifestyle factors, such as diet and natural, bioactive food compounds, such as vitamins, modify epigenetic patterns. However, epigenetic dysregulation can increase the risk of many diseases, including cancer. Various studies have provided supporting and contrasting evidence on the relationship between vitamins and cancer risk. Though there is a gap in knowledge about whether dietary vitamins can induce epigenetic modifications in the context of colorectal cancer (CRC), the possibility of using them as epidrugs for CRC treatment is being explored. This is promising because such studies might be informative about the most effective way to use vitamins in combination with DNA methyltransferase inhibitors and other approved therapies to prevent and treat CRC. This review summarizes the available epidemiological and observational studies involving dietary, circulating levels, and supplementation of vitamins and their relationship with CRC risk. Additionally, using available in vitro, in vivo, and human observational studies, the role of vitamins as potential epigenetic modifiers in CRC is discussed. This review is focused on the action of vitamins as modifiers of DNA methylation because aberrant DNA methylation, together with genetic alterations, can induce the initiation and progression of CRC. Although this review presents some studies with promising results, studies with better study designs are necessary. A thorough understanding of the underlying molecular mechanisms of vitamin-mediated epigenetic regulation of CRC genes can help identify effective therapeutic targets for CRC prevention and treatment.
Management and outcome of febrile neutropenia in admitted presumed immunocompetent patients with suspected viral illness
Authors: Morin Estelle M , Corriveau-Bourque Catherine , Foulds Jessica L
Published: August 2022

Objectives

Febrile neutropenia (FN) creates concern in paediatrics due to the risk of serious bacterial infections (SBI). Protocols with empiric antibiotics designed for hematology and oncology are often applied in healthy children with FN despite lower rates of SBI in this population. This study quantifies rates of infections in presumed immunocompetent children hospitalized with suspected viral illnesses and FN.

Methods

This was a retrospective chart review of healthy children admitted to the Stollery Children’s Hospital between 2007 and 2017 with fever, absolute neutrophil counts < 0.5 × 109/L, and viral symptoms. Primary outcomes were the incidence of SBI and bacterial pneumonia.

Results

Of 383 encounters reviewed, 96 admissions for 82 patients met inclusion criteria. Eighty-eight encounters (91.7%) were managed with empiric antibiotics. Viruses were identified in 42% of encounters. Three blood cultures were positive for coagulase-negative Staphylococcus and one for Coryneforms, all considered contaminants. There were three urinary tract infections and two pneumonias. Eighty-three per cent of patients had normalization of neutrophil counts, with a median neutropenia duration of 3.2 months. Follow-up diagnoses included chronic benign neutropenia of childhood (N = 17) and three rheumatologic/autoimmune conditions (N = 3).

Conclusion

Our results support previous findings of low rates of invasive bacterial infections in healthy children with FN. With an SBI rate of 3.1% and few patients found to have any pathologic etiology for their neutropenia, prospective studies would be valuable to evaluate the need for a practice change regarding antibiotic use in low-risk patients with suspected viral-induced neutropenia.
DALYs and the Minimally Good Life
Authors: Campbell Tim
Published: August 2022

Nicole Hassoun’s book Global Health Impact: Extending Access to Essential Medicines has three parts. Part 1 is about the right to health, Part 2 offers a concrete proposal for how to promote the ability of people in the developing world to live minimally good lives and Part 3 is concerned with consumer responsibility as it relates to global health. I argue that there is a philosophical tension between the respective projects of Parts 1 and 2. The project of Part 1 reflects a sufficientarian ideal, namely ensuring that each person in our global community has the ability to live a minimally good life. But, the concrete proposal offered in Part 2 reflects a different ideal, namely maximizing global health benefit. While these two ideals may often converge on a set of feasible health outcomes that we should aim to bring about, they can also diverge. The extent to which they diverge depends on our specification of the minimally good life. It is therefore crucial that we have a criterion for distinguishing lives that are at least minimally good from those that are not. Unfortunately, Hassoun’s proposed criterion is problematic in that no life satisfies it.
Telemedicine in Cancer Pain Management: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Buonanno Pasquale , Marra Annachiara , Iacovazzo Carmine , Franco Massimo , De Simone Stefania
Published: August 2022

Objective

Telemedicine is defined as the delivery of medical services through a variety of telecommunication tools. This novel approach can fit the needs of cancer patients who cannot often reach clinics due to their disabling symptoms. In this population of patients, pain is undoubtedly the most important symptom which dramatically affects the quality of life. Our work aimed to investigate the effectiveness of telemedicine in the management of cancer pain in order to assess the feasibility of a combination between telemedicine and traditional in-person visits; we also propose a model of integration of these two approaches.

Methods

We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework to conduct our study. Quality assessment and risk of bias were performed according Cochrane criteria. Results were reported as mean differences and summarized using forest plots. We performed a trial sequential analysis (TSA) to assess the conclusiveness of our results.

Results

Pain severity score and pain interference were lower for patients treated with telemedicine compared to those undergoing classical management (mean difference: −0.408; P =< .001 and −0.492; P = .004, respectively). TSA confirmed that our results were statistically significant and pointed out the need of other studies to reach the required sample size. PROSPERO registration: CRD42022333260.

Conclusions

Telemedicine can be effectively used to manage cancer pain. This novel approach will certainly have a revolutionary economic and organizational impact on health care systems in the next future. Furthermore, the model herein proposed could help set up an algorithm to safely and efficiently implement telemedicine.
Percutaneous Radiofrequency Ablation for Trigeminal Neuralgia Management: A Randomized, Double-Blinded, Sham-Controlled Clinical Trial
Authors: Mansano André Marques , Frederico Thiago Nouer , Valentin Raquel Elisa B , Carmona Maria Jose Carvalho , Ashmawi Hazem Adel
Published: August 2022

Trigeminal neuralgia, considered by many the worst pain that humankind can experience, has been called “the suicide disease.” Neuroablative procedures are good options when conservative treatment fails to promote pain relief or in those whose side effects are unbearable.

The objective was to compare the effectiveness and safety of trigeminal percutaneous radiofrequency ablation in classical refractory trigeminal neuralgia in a prospective, randomized, double-blind, sham-controlled clinical trial. We included 30 consecutive patients with classical trigeminal neuralgia who had failed to respond to drug treatment. The patients were randomly assigned into two groups: a thermal radiofrequency and a sham group. The thermal radiofrequency group were submitted to a 75°C lesion for 60 seconds after proper sensory and motor stimulation. All steps were carried out in the sham group except the thermal lesion. Patients were evaluated using the Numerical Rating Scale (NRS), the 36-Item Short-Form Health Survey questionnaire, and anticonvulsant dose.

After 1 month, the mean NRS score decreased from 9.2 to 0.7 in the radiofrequency group and from 8.9 to 5.8 in the sham group. This significant reduction was measurable starting at day one after the procedure and remained significant throughout the first month. Changing groups was allowed after one month, after which the pain reduction was similar between the two groups. Percutaneous trigeminal radiofrequency ablation results in statistically and clinically significant greater pain relief than the sham procedure after 1 month of follow-up. These results support using radiofrequency nerve ablation as a treatment for refractory trigeminal neuralgia.
Curve Characteristics and Surgical Outcomes in Scoliosis Associated With Childhood Sternotomy or Thoracotomy
Authors: Langner Joanna L. , Ezeonu Teeto , Shafau Abdul-Lateef , Javier Nadine , Bryson Xochitl , Kaur Japsimran , Poppino Kiley , Shivers Claire , Chilakapati Sai , Hall Kimberly E. , Imrie Meghan N. , Rinsky Lawrence , Riccio Anthony I. , Vorhies John S.
Published: August 2022

Background:

The purpose of this study is to describe curve characteristics and postoperative outcomes in patients undergoing spinal fusion (SF) to treat thoracogenic scoliosis related to sternotomy and/or thoracotomy as a growing child.

Methods:

A retrospective review of electronic medical records of all patients with Post-Chest Incision scoliosis treated with SF was performed at 2 tertiary care pediatric institutions over a 19-year period. Curve characteristics, inpatient, and outpatient postoperative outcomes are reported.

Results:

Thirty-nine patients (62% female) were identified. Eighteen had sternotomy alone, 14 had thoracotomy alone, and 7 had both. Mean age at the time of first chest wall surgery was 2.5 years (range: 1.0 d to 14.2 y). Eighty-five percent of patients had a main thoracic curve (mean major curve angle 72 degrees, range: 40 to 116 degrees) and 15% had a main lumbar curve (mean major curve angle 76 degrees, range: 59 to 83 degrees). Mean thoracic kyphosis was 40 degrees (range: 4 to 84 degrees). Mean age at the time of SF was 14 years (range: 8.2 to 19.9 y). Thirty-six patients had posterior fusions and 3 had combined anterior/posterior. Mean coronal curve correction measured at the first postoperative encounter was 53% (range: 9% to 78%). There were 5 (13%) neuromonitoring alerts and 2 (5%) patients with transient neurological deficits. Mean length of hospital stay was 9±13 days. At an average follow-up time of 3.1±2.4 years, 17 complications (10 medical and 7 surgical) were noted in 9 patients for an overall complication rate of 23%. There was 1 spinal reoperation in the cohort. 2/17 (12%) complications were Clavien–Dindo-Sink class III and 5/17 (29%) were class IV.

Conclusion:

Kyphotic thoracic curves predominate in patients with Post-Chest Incision scoliosis undergoing SF. Although good coronal and sagittal plane deformity can be expected after a fusion procedure, postoperative complications are not uncommon in medically complex patients, often necessitating longer postoperative stays.

Level of Evidence:

Level III.
How to reduce bacillus Calmette-Guérin discontinuation in patients with severe functional impairment
Authors: Di Gianfrancesco Luca , Ragonese Mauro , Foti Massimiliano , Palermo Giuseppe , Sacco Emilio , Bassi PierFrancesco , Racioppi Marco
Published: August 2022

Background

Severe functional impairment is often considered a contraindication to intravesical therapy for nonmuscle-invasive bladder cancer (NMIBC). A tailored intravesical bacillus Calmette-Guérin (BCG) procedure was evaluated in high-risk (HR)-NMIBC patients with severe functional impairment.

Materials and methods

Patients with a Katz Index score of 2 or less and an initial diagnosis of HR-NMIBC with atraumatic insertion of a Foley-type indwelling catheter, bladder emptying, and BCG instillation were prospectively treated; after 2 hours, the bladder was emptied and the catheter was removed (group A).

After propensity score matching, 52 patients in group A were compared with that of 52 consecutive patients in group B using a retrospective database, with similar baseline/oncological characteristics and treated with standard intermittent catheterization. Moreover, groups A and B were compared with that of 130 consecutive patients (group C) retrospectively evaluated, with similar oncological characteristics but with a Katz Index score of 3 or greater and treated with standard intermittent catheterization.

Results

The discontinuation rates were 11.5%, 35%, and 9% in groups A, B, and C, respectively (A vs. B, log-rank score 42.52 [p < 0.05]; B vs. C, 107.6 [p < 0.05]; A vs. C, 3.45 [p > 0.05]). The overall adverse event rates were 38.5%, 57.7%, and 39.2%, respectively (A vs. B, p = 0.04; B vs. C, 0.03; A vs. C, 0.92). The rates of severe adverse events were 1.9%, 1.9%, and 1.5%, respectively, without statistically significant differences. The cumulative HR disease-free survival rates were 63.4%, 48%, and 69.2%, respectively (A vs. B, log-rank score 154.9 [p < 0.05]; B vs. C, 415 [p < 0.05]; A vs. C, 244 [p < 0.05]).

Conclusions

A tailored intravesical instillation procedure may reduce BCG discontinuation and adverse effects.
Phase retardation and corneal sublayer thickness repeatability using ultrahigh-resolution polarization-sensitive OCT
Authors: Patil Rahul , Shetty Rohit , Patel Yash , Pisharody Anchana , Narasimhan Raghav , Pircher Michael , Hitzenberger Christoph K. , Nuijts Rudy M.M.A. , Sinha Roy Abhijit
Published: August 2022

Purpose:

To assess phase retardation and corneal sublayer thickness repeatability using ultrahigh-resolution polarization-sensitive optical coherence tomography (PS-OCT).

Setting:

Narayana Nethralaya Eye Hospital, Bangalore.

Design:

Observational.

Methods:

In this study, all eyes were imaged using a custom-built ultrahigh-resolution PS-OCT and high-resolution hybrid OCT (MS-39). The repeatability of phase retardation en face maps and corneal sublayer thickness profiles was evaluated. The reflectivity and phase retardation were calculated from the 2 orthogonal polarization channels to generate en face maps of phase retardation and corneal sublayer thicknesses. 3 consecutive measurements of all participants were acquired for each eye. For each measurement, the participant was asked to sit back and was realigned again. The repeatability was assessed using the intraclass correlation coefficient (ICC).

Results:

The study included 20 healthy eyes of 20 participants. The phase retardation en face maps showed preferential arrangement of collagen fibrils with least retardation in the apex and maximum retardation in the periphery. The phase retardation showed excellent repeatability (ICC >0.95) in all zones. The Bowman layer and stromal layer thicknesses were measured with excellent repeatability (ICC >0.93 and >0.99, respectively). Significant differences (P < .05) in stromal layer thickness were observed between MS-39 and PS-OCT. The repeatability of epithelial thickness measurements was better with PS-OCT than MS-39.

Conclusions:

The combinational assessment of corneal birefringence and sublayer thicknesses shows the advanced potential of ultrahigh-resolution PS-OCT in routine clinical practice over current OCT devices.
Corneal opacities after small-incision lenticule extraction
Authors: Kartal Serdar , Nuijts Rudy M.M.A. , Hjortdal Jesper , Daya Sheraz , Kweon Kim Eung , Sekundo Walter , Ganesh Sri , Brar Sheetal , Moshirfar Majid , Hansen Annika M. , Payne Carter J.
Published: August 2022

A 36-year-old woman was referred to our clinic in October 2021 with suboptimal vision at intermediate and near distances and halos and photophobia after a small-incision lenticule extraction (SMILE) in December 2019. The patient needs to increase font size of her computer to 150% to read text, but images still appear blurred. She indicates that sunglasses seem to improve her contrast. Preoperatively, her refractive error was −2.5 diopters (D) and −2.25 D for right and left eyes. The optical zone size of the SMILE procedure was 6.8 mm. There is no further information available on the peroperative course of the SMILE procedure.

Her uncorrected distance visual acuity (UDVA) is 20/20 in both eyes and does not improve with correction. The Schirmer tear test is 14 to 13 mm. Slitlamp biomicroscopy of the right eye and the left eye reveals hyperreflective small opacities in the anterior one-third of the corneal stroma (Figures 1 and 2

JOURNAL/jcrs/04.03/02158034-202209000-00021/figure1/v/2023-08-19T002640Z/r/image-tiff

JOURNAL/jcrs/04.03/02158034-202209000-00021/figure2/v/2023-08-19T002640Z/r/image-tiff

). No other abnormalities are seen.

The scotopic pupil sizes are 6.41 and 6.73 mm. Straylight measurements are within normal limits. Higher-order aberrations (HOAs) measure for the right eye (6.03 mm pupil) 0.818 μm and for the left eye (6.17 mm pupil) 0.560 μm. The corneal Scheimpflug tomography quad maps for both eyes are shown in Supplemental Figures 1 and 2 (http://links.lww.com/JRS/A663, http://links.lww.com/JRS/A664).

What is your diagnosis or are additional diagnostic methodologies needed to establish a diagnosis? What is your treatment advice for this patient?
Comparative study of refractive and visual quality after wavefront-optimized FS-LASIK for angle kappa adjustment in dominant and nondominant eyes
Authors: Lin Shuhua , Liu Hong-Bo , Zhao Jinghua , Li Yingjun
Published: August 2022

Purpose:

To investigate the differences between dominant and nondominant eyes in femtosecond laser–assisted laser in situ keratomileusis (FS-LASIK) with 50% angle kappa compensation on diopter and visual quality.

Setting:

University hospital.

Design:

Retrospective clinical study.

Methods:

109 patients (218 eyes, 100%) with myopia who underwent FS-LASIK were randomly selected. The preoperative pupil size, center position, and offset between the coaxially sighted corneal light reflex (P-Dist) of the patients was recorded. In preoperative and postoperative 6 months, an iTrace wavefront aberrometer was used to measure the corneal, internal optics, and total aberrations.

Results:

The 6 months postoperatively for corneal coma of the dominant eyes were 0.141 ± 0.055 μm and the nondominant eyes were 0.157 ± 0.033 μm, which was significantly greater than the dominant eyes (P = .028). The postoperative corneal coma aberration changes were positively correlated with preoperative P-Dist, the dominant eyes (r = 0.221, P = .023), and the nondominant eyes (r = 0.251, P = .009).

Conclusions:

Adjusting the angle kappa percentage in the nondominant eyes to be higher than that of the dominant eyes in individualized corneal refractive surgery may help find the ablation center closest to the visual axis.
The Clinical and Economic Burden of Tardive Dyskinesia in Israel
Authors: Barer Yael , Ribalov Rinat , Yaari Ayelet , Maor Ron , Arow Qais , Logan John , Chodick Gabriel , Arkadir David , Eitan Renana
Published: August 2022

Purpose/Background

Tardive dyskinesia (TD) is a hyperkinetic movement disorder caused by exposure to dopamine-receptor blockers. Data on TD burden in Israel are scarce. This analysis assesses the clinical and economic burden of TD in Israeli patients.

Methods/Procedures

This retrospective analysis used a national health plan database (Maccabi Healthcare Services), representing 25% of the Israeli population. The study included adults alive at index date with an International Classification of Diseases, Ninth Revision, Clinical Modification TD diagnosis before 2018 and more than or equal to 1-year enrollment before diagnosis. Tardive dyskinesia patients were matched to non-TD patients (1:3) by underlying psychiatric condition, birth year, and sex. Treatment patterns and 2018 annual health care resource utilization and costs were assessed.

Findings/Results

Of 454 TD patients alive between 2013 and 2018, 333 alive on January 1, 2018, were matched to 999 non-TD patients. At baseline, TD patients had lower socioeconomic status and higher proportion of chronic kidney disease and antipsychotic medication use; all analyses were adjusted accordingly. Tardive dyskinesia patients had significantly more visits to general physicians, neurologists, psychiatrists, physiotherapists, and emergency departments versus non-TD patients (all P < 0.05). Tardive dyskinesia patients also had significantly longer hospital stays than non-TD patients (P = 0.003). Total healthcare and medication costs per patient were significantly higher in the TD versus non-TD population (US $11,079 vs US $7145, P = 0.018).

Implications/Conclusions

Israeli TD patients have higher clinical and economic burden than non-TD patients. Understanding real-world health care resource utilization and costs allows clinicians and decision makers to quantify TD burden and prioritize resources for TD patients' treatment.
Prevalence and Risk Factors of Sarcopenia in Patients with Dizziness
Authors: Kamo Tomohiko , Ogihara Hirofumi , Tanaka Ryozo , Kato Takumi , Azami Masato , Tsunoda Reiko , Fushiki Hiroaki
Published: August 2022

Objective

This study aimed to investigate the prevalence of sarcopenia and factors associated with sarcopenia in patients with dizziness.

Study Design

This is a cross-sectional study.

Patients

A total of 162 patients 65 years or older with the chief complaint of dizziness or vertigo (dizziness group) and 132 community-dwelling elderly (control group) were recruited during their visit to the otolaryngology clinic between May 2020 and October 2021.

Results

Of the 162 patients with dizziness (dizziness group), 53 (32.7%) were classified as sarcopenia according to the 2019 criteria of the Asian Working Group for Sarcopenia. There were significant differences in the prevalence of sarcopenia between the dizziness group and the control group (p < 0.01). The factors that significantly affected the sarcopenia, in order of greater odds ratio, were HADS_A, age, and DHI_Total (odds ratio = 1.223, 1.130, and 1.022, respectively).

Conclusions

The present study shows that (i) the prevalence of sarcopenia in patients with dizziness is higher than a community-dwelling elderly; (ii) patients with dizziness and sarcopenia have higher DHI_functional, DHI_emotional, DHI_total, and HADS_A compared with patients with dizziness but without sarcopenia; and (iii) age, HADS_A, and DHI were associated with sarcopenia in patients with dizziness.
Screening for Child Abuse in Children With Isolated Skull Fractures
Authors: Chen Stephanie Y. , Gao Leland , Imagawa Karen Kay , Roseman Eric R. , Shin Cathy E. , Kim Eugene S. , Spurrier Ryan G.
Published: August 2022

Objective

Head trauma is the most common cause of death from child abuse, and each encounter for recurrent abuse is associated with greater morbidity. Isolated skull fractures (ISF) are often treated conservatively in the emergency department (ED). We determined patterns of physical abuse screening in a children's hospital ED for children with ISF.

Methods

A retrospective review was performed for children aged 3 years and younger who presented to the ED with ISF from January 1, 2015 to December 31, 2019. Children were stratified by age (<12 mo, ≥12 mo) and witnessed versus unwitnessed injury. Primary outcome was social work (SW) assessment to prescreen for abuse. Secondary outcomes were suspicion for abuse based on Child Protective Services (CPS) referral and subsequent ED encounters within 1 year.

Results

Sixty-six ISF patients were identified. Of unwitnessed injury patients aged younger than 12 months (n = 17/22), 88.2% (n = 15/17) underwent SW assessment and 47.1% (n = 8/17) required CPS referral. Of witnessed injury patients aged younger than 12 months (n = 23/44), 60.9% (n = 14/23) underwent SW assessment, with no CPS referrals. Overall, 18.2% (n = 4/22) unwitnessed and 20.5% (n = 9/44) witnessed injury patients returned to our ED: 2 were aged younger than 12 months and had recurrent trauma.

Conclusions

To decrease risk of missed physical abuse, SW consultation should be considered for all ISF patients.
Surgical Challenges in the Management of Post COVID-19 Midface Mucormycosis (PCoMM): An Institutional Protocol
Authors: Tomar Kapil , Roy Indranil Deb , Natarajan Mohan Rangan , Singh Anup Kumar , Ramanujam Vasanthanarayanan
Published: August 2022

Background:

The coronavirus disease 2019 (COVID-19) pandemic has posed another serious threat, mucormycosis infection, affecting the maxilla and orbitocerebral region. This condition has not spared world population from its merciless claws. This article addresses the challenges faced by the maxillofacial surgeons in setting the protocols from preoperative diagnosis, surgical management to postoperative care, including short-term and long-term rehabilitation. To manage this relentlessly progressing condition, a multispecialty team approach is to be activated in diagnosing, managing, and rehabilitating the patients.

Purpose:

The purpose of this clinical study is to document and analyze the clinical and demographic data, presentation of the lesion, the diagnostic methods followed for early clinical detection, and management of post COVID-19 midface mucormycosis. The article also discusses postoperative medical management and prosthetic rehabilitation.

Results:

Most of the mucormycosis cases reporting to our center were treated and recovered patients of Severe Acute Respiratory Syndrome Coronavirus 2 infection. Thirty-four (n=34) case were operated for post COVID-19 midface mucormycosis between October 2020 and December 2021. Male to Female ratio is 1:42. The average age of the patients was 57.5 years. Maximum patients were in fifth and sixth decade of life. Maxilla was the involved bone. Treatment was primarily surgical debridement to extended or radical maxillectomy. All patients were treated with Liposomal Amphotericin B and tab posaconazole for 3 to 4 weeks depending upon the age, weight, and physiological state of the patients to attain an optimal cumulative load. Three patients succumbed to illness postoperatively (n=3, 1.02%). Average duration of hospital stay was 47 days. The average review period was 5.1 months.
INTRAPULMONARY TREATMENT WITH A NOVEL TLR4 AGONIST CONFERS PROTECTION AGAINST KLEBSIELLA PNEUMONIA
Authors: Hernandez Antonio , Zhou Jing , Bohannon Julia K. , McBride Margaret A. , Gibson-Corley Katherine N. , Patil Naeem K. , Owen Allison M. , Burelbach Katherine R. , Sherwood Edward R.
Published: August 2022

Objectives: Nosocomial pneumonia is a common complication in critically ill patients. The goal of this study was to examine the efficacy of the Toll-like receptor 4 agonist 3-deacyl phosphorylated hexacyl disaccharide (3D PHAD), in a clinically relevant murine model of pneumonia, and assess the cellular mechanisms that mediate the protective response. Design: Mice received intrapulmonary 3D PHAD (20 μg) or vehicle for 2 consecutive days before challenge with intrapulmonary Klebsiella pneumoniae (2.3 × 103 colony-forming units). Mice were followed for 14-day survival, pulmonary K. pneumoniae burden, lung leukocyte profile, leukocyte phagocytic capacity, and cytokine production. Pneumonia severity and leukocyte recruitment were further assessed by histological evaluation. Setting: Research laboratory. Subjects: Wild-type, male C57BL/6 J mice. Interventions: Intrapulmonary treatment with 20 μg 3D PHAD for 2 consecutive days. Measurements and main results: Intrapulmonary treatment with 3D PHAD decreased lung K. pneumoniae colony-forming units and pneumonia severity with an associated improvement in survival compared with mice treated with vehicle. The numbers of neutrophils, monocytes, and macrophages in the lungs of 3D PHAD–treated mice were higher than those in vehicle-treated mice before infection but were not significantly different from vehicle-treated mice at 48 h after K. pneumoniae challenge. Lung innate leukocytes from 3D PHAD–treated mice had increased phagocytic capacity. Treatment with 3D PHAD alone increased cytokines in the lungs but decreased cytokines in plasma during K. pneumoniae pneumonia as compared with control. Conclusions: Intrapulmonary treatment with 3D PHAD augments innate immunity in the lung and facilitates resistance to K. pneumoniae pneumonia.
Evaluation of the Diagnostic Performance of urine dipstick test for Detection of urinary tract infections in patients treated in Kenyan hospitals.
Authors: Maina John , Mwaniki John , Mwiti Franklin , Kiiru Susan , Katana Japhet , Wanja Fredrick , Mukaya Joel , Khasabuli Osborn , Kiiru John
Published: August 2022

Introduction
Culture is the gold-standard diagnosis for Urinary Tract Infections (UTIs). However, most hospitals in poor-resource countries lack adequately equipped laboratories and relevant expertise to perform culture and therefore heavily rely on dipstick tests as an alternative diagnostic method for UTIs.
Research gap
In many Kenyan hospitals, routine evaluations are rarely done to assess the reliability of popular screening tests such as the dipstick test. As such, there is a high risk of misdiagnosis emanating from inappropriate or insufficient use of proxy screening tests over the goal standards. As a result, this may lead to misuse, under-use, or over-use of antimicrobials and treatment failure.  
Aim
The present study sought to assess the reliability of the urine dipstick test as a proxy for the diagnosis of urinary tract infections in selected Kenyan hospitals.
Results
Using a cross-sectional hospital-based approach, the present study evaluated the performance of urine dipstick test in UTI diagnosis using culture as the gold standard. A UTI prevalence of 54.1% was found using culture. This was lower than the 66.4% recorded by the dipstick test. Estimated UTI prevalence by Nitrate test, RBCs, and Leukocyte's esterase (L.E) was 11.9%, 28.1 %, and 46%, which were lower than the observed. The nitrate test had a sensitivity of 19.8%, which was lower than 32.9%, 65.5%, and 66.2% by RBCs, all dipstick parameters, and L.E, respectively. Nitrate test (97.4%) and RBCs (77.6%) had a better specificity compared to L.E (56.5%) and all dipstick parameters combined (68.3%).
Conclusion
The prevalence discrepancies from the observed and low sensitivity and Specificity imply dipstick test inadequacy for accurate UTI diagnosis. The finding also demonstrates the need for urine culture for accurate UTI diagnosis.
Exosomes from WSSV-infected shrimp contain viral components that mediate virus infection
Authors: Sun Xumei , Zhang Siyuan
Published: August 2022

Exosomes have been described as vesicles that mediate intercellular communication and thus affect normal and pathological processes. Furthermore, many viruses have been reported to deliver viral components to host cells through exosomes. However, the roles of exosomes in invertebrates response to virus infection are poorly understood. In this study, we found that exosomes purified from white spot syndrome virus (WSSV)-infected hemocytes of shrimp could promote viral replication. These exosomes contained WSSV genomic DNA and nucleocapsid protein VP15, suggesting that exosomes can transfer viral genetic materials between cells, although the exosomes did not have similar infection ability to viruses. Remarkably, in exosomes WSSV DNA was bound to VP15 protein, and moreover VP15 silencing significantly suppressed WSSV infection and reduced the WSSV genome fragments in exosomes, indicating that the presence of VP15 is required for the packing of WSSV DNA inside the exosomes and thereby assists virus to complete immune escape. The above results not only contribute to elucidation of the infection and transmission mechanisms of WSSV, but are also of great significance for further study of virus–host interaction and reasonable prevention measures. Taken together, our findings provide a novel insight into the regulation of virus transmission via exosomes and highlight potential therapeutic strategies.
Knockout of Dicer-2 in the Sf9 cell line enhances the replication of Spodoptera frugiperda rhabdovirus and conditionally increases baculovirus replication
Authors: de Malmanche Henry , Hussain Mazhar , Marcellin Esteban , Reid Steve , Asgari Sassan
Published: August 2022

The Sf9 cell line, originally isolated from the ovarian tissue of Spodoptera frugiperda larvae, is widely used in academia and industry for the baculovirus-mediated production of recombinant proteins and virus-like particles. RNA interference (RNAi) is a conserved antiviral pathway present in eukaryotic organisms and is the primary antiviral defence mechanism in insects. Recent evidence has implicated RNAi as an antiviral response to baculovirus infection in Sf9 cells. To test this hypothesis, CRISPR/Cas9 technology was used to disable the RNAi pathway in Sf9 cells by knocking out Dicer-2, the protein responsible for cleaving viral double-stranded RNA precursors into short interfering RNAs. Infection of Dicer-2 knockout Sf9 cells with either the wild-type baculovirus Autographa californica nucleopolyhedrovirus (AcMNPV), recombinant AcMNPV (rAcMNPV) expressing β-galactosidase (β-gal), or rAcMNPV expressing a wasp venom protein (Vn50) at a multiplicity of infection (m.o.i.) of 1 resulted in a modest increase in virus replication compared to control Sf9 cells under adherent culture conditions. In contrast, Dicer-2 knockout Sf9 monolayer or suspension cultures infected by the rAcMNPV expressing β-gal at higher m.o.i.s (3.5 and 20) did not exhibit increases in either viral DNA replication or β-gal production. Intriguingly, during long-term passaging in suspension, Dicer-2 knockout Sf9 cultures underwent transient crashes in cell proliferation and viability. It was discovered that these periods of low growth and viability coincided with a dramatic increase in the RNA levels of S. frugiperda rhabdovirus, a recently identified adventitious virus that persistently infects the Sf9 cell line, suggesting a role for Dicer-2 in managing chronic viral infections in this industrially relevant insect cell line.
Epigenetic memory acquired during long-term EMT induction governs the recovery to the epithelial state
Authors: Jain Paras , Corbo Sophia , Mohammad Kulsoom , George Jason T , Levine Herbert , Toneff Michael , Jolly Mohit Kumar
Published: August 2022

Epithelial-Mesenchymal Transition (EMT) and its reverse Mesenchymal-Epithelial Transition (MET) are critical during embryonic development, wound healing and cancer metastasis. While phenotypic changes during short-term EMT induction are reversible, long-term EMT induction has been often associated with irreversibility. Here, we show that phenotypic changes seen in MCF10A cells upon long-term EMT induction by TGFβ need not be irreversible, but have relatively longer timescales of reversibility than those seen in short-term induction. Next, using a phenomenological mathematical model incorporating the epigenetic silencing of miR-200 by ZEB, we highlight how the epigenetic memory gained during long-term EMT induction can slow the recovery to the epithelial state post-TGFβ withdrawal. Our results suggest that epigenetic modifiers can govern the extent and timescale of EMT reversibility, and advise caution against labelling phenotypic changes seen in long-term EMT induction as ‘irreversible’.
A dynamic sequence of visual processing initiated by gaze shifts
Authors: Parker Philip R. L. , Martins Dylan M. , Leonard Emmalyn S. P. , Casey Nathan M. , Sharp Shelby L. , Abe Elliott T. T. , Smear Matthew C. , Yates Jacob L. , Mitchell Jude F. , Niell Cristopher M.
Published: August 2022

Animals move their head and eyes as they explore and sample the visual scene. Previous studies have demonstrated neural correlates of head and eye movements in rodent primary visual cortex (V1), but the sources and computational roles of these signals are unclear. We addressed this by combining measurement of head and eye movements with high density neural recordings in freely moving mice. V1 neurons responded primarily to gaze shifts, where head movements are accompanied by saccadic eye movements, but not to head movements where compensatory eye movements stabilize gaze. A variety of activity patterns immediately followed gaze shifts, including units with positive, biphasic, or negative responses, and together these responses formed a temporal sequence following the gaze shift. These responses were greatly diminished in the dark for the vast majority of units, replaced by a uniform suppression of activity, and were similar to those evoked by sequentially flashed stimuli in head-fixed conditions, suggesting that gaze shift transients represent the temporal response to the rapid onset of new visual input. Notably, neurons responded in a sequence that matches their spatial frequency preference, from low to high spatial frequency tuning, consistent with coarse-to-fine processing of the visual scene following each gaze shift. Recordings in foveal V1 of freely gazing head-fixed marmosets revealed a similar sequence of temporal response following a saccade, as well as the progression of spatial frequency tuning. Together, our results demonstrate that active vision in both mice and marmosets consists of a dynamic temporal sequence of neural activity associated with visual sampling.

Highlights

During free movement, neurons in mouse V1 respond to head movements that are accompanied by a gaze-shifting saccadic eye movement, but not a compensatory eye movement.

Neurons respond to gaze shifts with diverse temporal dynamics that form a sequence across the population, from early positive responses to biphasic and negative responses.

In darkness, most neurons show a uniform suppression following a gaze shift.

Temporal dynamics of responses correspond to a neuron’s temporal and spatial frequency preferences, consistent with a coarse-to-fine processing sequence.

A similar temporal sequence following saccades is observed in foveal V1 of freely gazing head-fixed marmosets, demonstrating shared aspects of active visual processing across species.
The impact of maternal dietary folic acid or choline deficiencies on cerebral blood flow, cardiac, aortic, and coronary function in young and middle-aged female mouse offspring following ischemic stroke
Authors: Pull Kasey , Folk Robert , Kang Jeemin , Jackson Shaley , Gusek Brikena , Esfandiarei Mitra , Jadavji Nafisa M.
Published: August 2022

Background and Purpose

Adequate maternal dietary levels of one-carbon (1C) metabolites, such as folic acid and choline, play an important role in the closure of the neural tubein utero; however, the impact of deficiencies in 1C on offspring neurological function after birth remain undefined. Stroke is one of the leading causes of death and disability globally. The aim of our study was to determine the impact of maternal 1C nutritional deficiencies on cerebral and peripheral blood flow after ischemic stroke in adult female offspring.

Method

In this study, female mice were placed on either control (CD), folic acid (FADD), or choline (ChDD) deficient diets prior to pregnancy. Female offspring were weaned onto a CD for the duration of the study. Ischemic stroke was induced in offspring and after six weeks cerebral and peripheral blood flow velocity was measured using ultrasound imaging.

Results

Our data showed that 11.5-month-old female offspring from ChDD mothers had reduced blood flow in the posterior cerebral artery compared to controls. In peripheral blood flow velocity measurements, we report an aging effect.

Conclusions

These results emphasize the importance of maternal 1C diet in early life neuro-programming on long-term vasculature health.
Co-infection of Ehrlichia with B. burgdorferi drives emergency myelopoiesis and promotes Lyme arthritis
Authors: Bonin Jesse L. , Torres Steven R. , Marcinkiewicz Ashley L. , Yang Xiuli , Pal Utpal , DiSpirito Julia M. , Nowak Tristan , Lin Yi-Pin , MacNamara Katherine C.
Published: August 2022

Lyme disease is caused by the extracellular pathogen Borrelia burgdorferi (Bb), transmitted by the Ixodes scapularis tick. Approximately one-third of infected individuals develop arthritis of weight-bearing joints, though it is unclear why some patients develop arthritis and severe systemic disease while others do not. C57BL/6 (B6) mice are susceptible to Bb infection but do not develop arthritis, providing an in vivo model to evaluate mechanisms regulating development of Lyme arthritis. We demonstrate here that co-infection of B6 mice with the tick-borne pathogens Bb and Ehrlichia muris (Em) induced significant arthritis. Although co-infection did not impact bacterial burden or growth of either pathogen, the resultant Lyme arthritis in co-infected mice correlated with significant hematologic disturbances. Whereas single Bb infection elicited no overt hematologic changes, Em infection resulted in thrombocytopenia, lymphopenia, monocytosis, and granulocytosis, which was consistently observed in mice co-infected with both Bb and Em. Hematologic changes correlated with profound changes to the hematopoietic stem and progenitor cell (HSPC) populations in Em-infected mice. Most notable were dramatic reductions in populations of HSPCs committed to myeloid-biased differentiation. Co-infection resulted in persistent hematologic changes and bone marrow inflammation. Our data demonstrate for the first time that B6 mice, resistant to developing Lyme arthritis, exhibit severe joint pathology in the presence of a second pathogen, correlating with persistent emergency myelopoiesis. Our data support the conclusion that pathogen burden is not sufficient for disease and specific inflammatory signals and cells regulate the development of Lyme arthritis.

Importance

Tick-borne illnesses, historically relegated to specific geographic areas, are increasing in prevalence and distribution. Borrelia burgdorferi causes Lyme disease, the most common tick-borne illness in North America, characterized by debilitating arthritis, carditis, and neurologic complications. It remains unclear why certain infected individuals develop severe disease while others are only mildly symptomatic. Human monocytic ehrlichiosis (HME) is another tick-borne disease that often results in profound illness and severe hematological disturbances. We show here that co-infection of B6 mice, resistant to Lyme arthritis, with Borrelia burgdorferi and Ehrlichia muris, used to model HME, results in the development of severe arthritis and emergency myelopoiesis. Our work suggests that immune activation driven by co-infection contributes to the development of Lyme arthritis.
Identification of 64 new risk loci for major depression, refinement of the genetic architecture and risk prediction of recurrence and comorbidities
Authors: Als Thomas D. , Kurki Mitja , Grove Jakob , Voloudakis Georgios , Therrien Karen , Tasanko Elisa , Nielsen Trine Tollerup , Naamanka Joonas , Veerapen Kumar , Levey Daniel , Bendl Jaroslav , Bybjerg-Grauholm Jonas , Zheng Biao , Demontis Ditte , Rosengren Anders , Athanasiadis Georgios , Bækved-Hansen Marie , Qvist Per , Walters Bragi , Thorgeirsson Thorgeir , Stefánsson Hreinn , Musliner Katherine L , Manikandan Veera , Farajzadeh Leila , Thirstrup Janne , Vilhjálmsson Bjarni J. , McGrath John J. , Mattheisen Manuel , Meier Sandra ,   iPSYCH-Broad Consortium, Agerbo Esben , Stefánsson Kári , Nordentoft Merete , Werge Thomas , Hougaard David M. , Mortensen Preben B. , Stein Murray , Gelernter Joel , Hovatta Iiris , Roussos Panos , Daly Mark J. , Mors Ole , Palotie Aarno , Børglum Anders D.
Published: August 2022

Major depression (MD) is a common mental disorder and a leading cause of disability worldwide. We conducted a GWAS meta-analysis of more than 1.3 million individuals, including 371,184 with MD, identifying 243 risk loci. Sixty-four loci are novel, including glutamate and GABA receptors that are targets for antidepressant drugs. Several biological pathways and components were enriched for genetic MD risk, implicating neuronal development and function. Intersection with functional genomics data prioritized likely causal genes and revealed novel enrichment of prenatal GABAergic neurons, astrocytes and oligodendrocyte lineages.

We found MD to be highly polygenic, with around 11,700 variants explaining 90% of the SNP heritability. Bivariate Gaussian mixture modeling estimated that > 97% of risk variants for other psychiatric disorders (anxiety, schizophrenia, bipolar disorder and ADHD) are influencing MD risk when both concordant and discordant variants are considered, and nearly all MD risk variants influence educational attainment. Additionally, we demonstrated that MD genetic risk is associated with impaired complex cognition, including verbal reasoning, attention, abstraction and mental flexibility.

Analyzing Danish nation-wide longitudinal data, we dissected the genetic and clinical heterogeneity, revealing distinct polygenic architectures across case subgroups of MD recurrency and psychiatric comorbidity and demonstrating two-to six-fold increases in absolute risks for developing comorbid psychiatric disorders among MD cases with the highest versus the lowest polygenic burden.

The results deepen the understanding of the biology underlying MD and its progression and inform precision medicine approaches in MD.