bluuebunny/crossref_metadata_2025 huggingface dataset:
P050 Familiar locations and new locations: sleep’s role in the consolidation of spatial navigation information using a novel virtual Morris water maze task in older adults with mild cognitive impairment
Authors: Haroutonian C , Johnston I , Ricciardiello A , Lam A , Grunstein R , D’Rozario A , Naismith S
Published: October 2021

Introduction

The ability to navigate oneself in space is one of the first functional impairments in Alzheimer’s disease (AD). A 3D-computerised spatial navigation (SN) task was designed to delineate, for the first time in a sleep-dependent memory paradigm, egocentric and allocentric SN, the latter identified as one cognitive biomarker of AD. We examined group differences in SN memory and associations with sleep macroarchitecture.

Methods

Older adults with mild cognitive impairment (MCI, n=32) and controls (n=25) underwent overnight polysomnography and completed the SN task before and after sleep. Participants learnt the location of a target over 5 trials (familiar location; egocentric-dependent), then were instructed to find the target from a novel start location (allocentric-dependent). Memory % retention (MR) from both start locations were calculated by the XY coordinate of marked location to correct location of the target, pre- and post-sleep. Navigational strategies were coded using self-reported description of how participants’ found the target. Associations between MR with REM and SWS % duration, and AHI in REM and NREM were examined using Spearman’s correlations.

Results

Repeated-measures ANOVA showed Controls MR improved overnight whereas MCI performed worse (F=7.46, p=.009), with greatest differences on familiar start location MR (p=.02). Strategy as a covariate revealed a location by strategy interaction (p=01). Novel location MR was associated with REM%, rho=.448, (p=.02) in Controls, and REM-AHI, rho=.400 (p=.02) in MCI.

Conclusion

Behavioural and self-reported results suggest disrupted SN strategies relative to environment in MCI. Future studies should examine SN in association with sleep-wake neurophysiology and neuronal integrity.
P110 The association between sleep spindles and cognitive function in middle-aged and older men: A community-based study
Authors: Parker J , Melaku Y , D’Rozario A , Wittert G , Martin S , Catcheside P , Lechat B , Teare A , Appleton S , Adams R , Vakulin A
Published: October 2021

Introduction

The association between sleep spindles and cognitive function and the potential confounding influence of obstructive sleep apnea (OSA) remains uncertain. This study examined cross-sectional associations between sleep spindle metrics and cognitive function outcomes in community-dwelling men.

Methods

Men, Androgen, Inflammation, Lifestyle, Environment, and Stress (MAILES) study participants (n=477) underwent home-based polysomnography between 2010–2011 and completed the inspection time task, trail-making test A (TMT-A) and B (TMT-B), and Fuld object memory evaluation. Frontal spindle metrics derived from sleep electroencephalography included occurrence (total no. of sleep spindle events) and slow (11–13 Hz) and fast (13–16 Hz) spindle density (no./min) during N2 and N3 sleep.

Results

Men with OSA (any OSA and severe OSA) had significantly impaired sleep spindles (reduced occurrence and densities). In the complete study sample, higher spindle occurrence during N2 sleep was independently associated with faster inspection time (B= -0.44, 95% CI [-0.87, -0.02], p=0.041), whereas higher fast spindle density during N3 sleep was independently associated with worse TMT-B performance (B=20.7, 95% CI [0.55, 40.9], p=0.044). Furthermore, in men with severe OSA (apnea-hypopnea index ≥30/h), higher slow spindle density during N2 sleep was independently associated with worse TMT-A and TMT-B performance, whereas only higher spindle occurrence during N2 sleep was independently associated with worse TMT-A performance (all p<0.05).

Discussion

Specific spindle metrics during N2 and N3 sleep are independently associated with cognitive function in an unselected population of men and men with undiagnosed severe OSA. The utility of sleep spindles for predicting cognitive dysfunction and decline requires further investigation.
P114 The effect of light interventions on sleep macro- and micro-architecture in sleep and circadian rhythm disorders: A scoping review
Authors: Pun T , Phillips C , Marshall N , Comas M , Hoyos C , D’Rozario A , Bartlett D , Davis W , Hu W , Naismith S , Cain S , Postnova S , Grunstein R , Gordon C
Published: October 2021

Introduction

Light interventions have been used to treat sleep and circadian rhythm disorders. However, there are limited studies on the effect of light on electroencephalographic (EEG) activity during sleep. Therefore, we aimed to provide an overview of research using light intervention on sleep macro- and micro-architecture.

Methods

We searched for randomised controlled trials that used light interventions and examined the effect on sleep measured using EEG in MEDLINE, PubMed, CINAHL, CENTRAL and PsycINFO databases. We included studies that examined the light intervention on sleep EEG in participants with a sleep or circadian rhythm disorder.

Results

Four studies met the inclusion criteria in patients with insomnia only. These studies reported only sleep macro-architecture outcomes with three studies showing no effect of the timing or intensity of light intervention on total sleep time, wake after sleep onset, sleep efficiency and sleep stage duration. Only one study reported a significantly higher sleep efficiency after night-time light intervention (>4,000 lx, 21:00-23:00 h) compared with afternoon light intervention (>4,000 lx, 15:00-17:00 h). However, none of these studies reported sleep micro-architecture (power spectral analysis).

Conclusion

Overall, there was limited evidence about the effect of light intervention on EEG sleep measures and studies were confined to insomnia patients only. This review could not find any data on sleep EEG spectral power related to light interventions. Research needs to be conducted into the effect of lighting interventions in clinical populations on sleep macro- and micro-architecture to better understand the effect on objective sleep timing and quality.
P119 CPAP and adverse cardiovascular events in OSA: Are participants of randomized trials representative of sleep clinic patients?
Authors: Reynor A , McArdle N , Shenoy B , Dhaliwal S , Rea S , Walsh J , Eastwood P , Maddison K , Hillman D , Ling I , Keenan B , Maislin G , Magalang U , Pack A , Mazzotti D , Lee R , Singh B
Published: October 2021

Introduction

Randomized controlled trials (RCTs) have shown no reduction in adverse cardiovascular (CV) events in patients randomized to continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA). This study examined whether randomized study populations were representative of OSA patients attending a sleep clinic.

Methods

Sleep clinic patients were 3,965 consecutive adults diagnosed with OSA by in-laboratory polysomnography from 2006–2010 at a tertiary hospital sleep clinic. Characteristics of these sleep clinic OSA patients were compared with participants of 5 well-known RCTs examining the effect of CPAP on adverse CV events in OSA. We determined the percentage of patients with severe (apnea hypopnea index, [AHI]≥30/h) or any OSA (AHI≥5/h) who met the selection criteria of each RCT, as well as identified those criteria that excluded the most patients.

Results

Compared to RCT participants, sleep clinic OSA patients were younger, sleepier, more likely to be female and less likely to have established CV disease. The percentage of patients with severe or any OSA who met the RCT selection criteria ranged from 1.2% to 20.2% and 0.8% to 21.1%, respectively. The selection criteria that excluded most patients were pre-existing CV disease, symptoms of excessive sleepiness, nocturnal hypoxemia and co-morbidities.

Discussion

A minority of sleep clinic patients diagnosed with OSA meet the selection criteria of RCTs of CPAP on adverse CV events in OSA. OSA populations in RCTs differ considerably from typical sleep clinic OSA patients. This suggests that the findings of RCTs may not be generalisable to most sleep clinic OSA patients.
P133 Backward Rotating Shifts are Associated with Real-Time Drowsiness During Daytime Drives in Heavy Vehicle Drivers
Authors: Shekari Soleimanloo S , Sletten T , Clark A , Cori J , Wolkow A , Beatty C , Shiferaw B , Barnes M , Tucker A , Anderson C , Rajaratnam S , Howard M
Published: October 2021

Purpose

While 10–20% of heavy vehicle crashes (HVDs) are drowsiness-related, the contributions of subsequent shifts to chronic drowsiness in HVDs is largely unknown. Eye-blink parameters indicate driver drowsiness reliably. This study examined the association of consecutive shifts and real-time drowsiness in HVDs.

Methods

Habitual sleep-wake of HVDs (all males, aged 49.5 ± 8 years) was monitored objectively (Philips Actiwatch, N=15) for 5 weeks (5.75± 1.4 hours). Johns Drowsiness Score (JDS, a composite eye-blink parameter in one-min intervals) was monitored for 4 weeks in HVDs (N=14) using an infrared oculography (Optalert, Melbourne, Australia) device. We assessed the association of drowsiness events (JDS equal or larger than 2.6) with consecutive shift types via mixed linear regression models.

Results

Eigth consecutive shifts increased drowsiness by 1.06 times compared to 2 shifts (8.37 events/h vs 6.77 events/h, P= 0.03). Consecutive shift sequences included afternoons (9%), mornings (29%), nights (5%), mixed rotating shifts (28%), forward-rotating shifts (11%) and backward-rotating shifts (12%). Drowsiness event rates were 1.23 times greater during night consecutive shifts relative to afternoon shifts (8.37 events/h vs 6.67 events/h, P= 0.03). Backward-rotating shifts (morning-night-evening- afternoon) elevated daytime drowsiness between 10 am and 3 pm by 1.55 times (10.01 events/h vs 6.47 events/h, P= 0.016).

Conclusions

Regardless of the number of consecutive shifts, sequential night shifts increase real-time drowsiness in HVDs, with backward rotating shifts resulting in higher rates of drowsiness events during daytime. The interaction of schedule features should inform the work scheduling of HVDs to reduce the risk of drowsiness.
P137 Deep learning enables accurate automatic sleep stage classification in a clinical paediatric population
Authors: Somaskandhan P , Korkalainen H , Terrill P , Sigurðardóttir S , Arnardóttir E , Ólafsdóttir K , Sigurðardóttir S , Clausen M , Töyräs J , Leppänen T
Published: October 2021

Introduction

Sleep disorders are widespread in children and associated with a myriad of detrimental health sequelae. Accurate identification of sleep stages is crucial in diagnosing various sleep disorders; however, manual sleep stage scoring can be subjective, laborious, and costly. To tackle these shortcomings, we aimed to develop an accurate deep learning-based approach to automate sleep staging in a paediatric cohort.

Methods

A clinical dataset (n=115, 35% girls) containing overnight polysomnographic recordings of 10–13-year-old Icelandic children from the EuroPrevall-iFAAM study was utilised to develop a combined convolutional and long short-term memory neural network architecture. A three-channel input comprising electroencephalography (F4-M1), electrooculography (E1-M2), and chin electromyography was used to train and evaluate the model to classify sleep into five stages (wake/N1/N2/N3/REM) using 10-fold cross-validation. Further, inter-rater reliabilities between two manual scorers and the automatic method were investigated in a subset (n=10) of the population.

Results

The automatic classification model achieved an accuracy of 84.5% (Cohen’s kappa κ=0.78: substantial agreement with manual scorings). Inter-rater reliability attained between two manual scorers was 84.6% (κ=0.78), and the automatic method achieved similar concordances with them, 83.4% (κ=0.76) and 82.7% (κ=0.75).

Discussion

The developed model achieved high accuracy and compared favourably to previously published state-of-the-art methods (performance range: 74.8%-84.3%). Inter-rater reliabilities were on par with the consensus between manual scorers and even better than among international sleep centres (commonly 0.57–0.63 as per literature). Therefore, incorporating the proposed methodology in clinical practice could be highly beneficial as it enables fast, cost-effective, and accurate sleep classification in children.
Call-In, Call-Out, Care, and Cool Rationality: How Young Adults Respond to Racism and Sexism Online
Authors: Ortiz Stephanie M
Published: October 2021

Despite the ubiquitous nature of racist and sexist discourses online, and evidence that racism and sexism are built into the architecture of online spaces, relatively little is known about how people respond to online inequalities. Using interview data with 60 young adults, I identify four response strategies which reproduce and contest racism and sexism in distinct ways. Viewing the problem as one of ignorance, white women and men of color are most likely to call-in and educate others about the emotional harm and fallacies of racism and sexism. Women of color call-out harassers, by rebutting misinformation and hate speech; they also check in, validate, and care for other women of color as a form of resistance. Focusing on so-called logic, facts, and cool rationality, white men intellectualize discrimination online. These responses are structured by race and gender, meaning they are outcomes of how discrimination is experienced and justified more broadly. This work draws further attention to the need to refine theories of racism and sexism, which do not yet take into account the cultural and structural implications of the consequences of online interactions.
Preoperative Paravertebral Block and Chronic Pain after Breast Cancer Surgery: A Double-blind Randomized Trial
Authors: Albi-Feldzer Aline , Dureau Sylvain , Ghimouz Abdelmalek , Raft Julien , Soubirou Jean-Luc , Gayraud Guillaume , Jayr Christian
Published: October 2021

Background

The effectiveness of paravertebral block in preventing chronic pain after breast surgery remains controversial. The primary hypothesis of this study was that paravertebral block reduces the incidence of chronic pain 3 months after breast cancer surgery.

Methods

In this prospective, multicenter, randomized, double-blind, parallel-group, placebo-controlled study, 380 women undergoing partial or complete mastectomy with or without lymph node dissection were randomized to receive preoperative paravertebral block with either 0.35 ml/kg 0.75% ropivacaine (paravertebral group) or saline (control group). Systemic multimodal analgesia was administered in both groups. The primary endpoint was the incidence of chronic pain with a visual analogue scale (VAS) score greater than or equal to 3 out of 10, 3 months after surgery. The secondary outcomes were acute pain, analgesic consumption, nausea and vomiting, chronic pain at 6 and 12 months, neuropathic pain, pain interference, anxiety, and depression.

Results

Overall, 178 patients received ropivacaine, and 174 received saline. At 3 months, chronic pain was reported in 93 of 178 (52.2%) and 83 of 174 (47.7%) patients in the paravertebral and control groups, respectively (odds ratio, 1.20 [95% CI, 0.79 to 1.82], P = 0.394). At 6 and 12 months, chronic pain occurred in 104 of 178 (58.4%) versus 79 of 174 (45.4%) and 105 of 178 (59.0%) versus 93 of 174 (53.4%) patients in the paravertebral and control groups, respectively. Greater acute postoperative pain was observed in the control group 0 to 2 h (area under the receiver operating characteristics curve at rest, 4.3 ± 2.8 vs. 2.9 ± 2.8 VAS score units × hours, P < 0.001) and when maximal in this interval (3.8 ± 2.1 vs. 2.5 ± 2.5, P < 0.001) but not during any other interval. Postoperative morphine use was 73% less in the paravertebral group (odds ratio, 0.272 [95% CI, 0.171 to 0.429]; P < 0.001).

Conclusions

Paravertebral block did not reduce the incidence of chronic pain after breast surgery. Paravertebral block did result in less immediate postoperative pain, but there were no other significant differences in postoperative outcomes.

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Effect of Postoperative Trimming of the Tube Portion of Ahmed Glaucoma Valve on Corneal Endothelial Cell Loss
Authors: Lee Ko Eun , Sung Kyung Rim , Shin Joong Won
Published: October 2021

Précis:

We reduced the tube length through a small limbal incision in eyes that underwent Ahmed glaucoma valve (AGV) implantation and found that the rate of corneal endothelial cell (CEC) density was markedly reduced from −12.2% per year to −3.5% per year after this simple procedure.

Purpose:

The aim was to evaluate the effect of postoperative tube tip trimming (TT) after AGV implantation on CEC loss.

Methods:

In this retrospective cohort study, a total of 75 eyes from 67 patients (41 eyes in the AGV implantation only group (AGVG: mean follow-up, 42.2±13.8 mo) and 34 eyes in the TT after AGV implantation group (TAGVG: mean follow-up, 64.9±18.5 mo) were analyzed. TT was performed through a small limbal incision at a mean of 41 months after AGV implantation. Both groups were followed up for at least 1 year and underwent at least 2 specular microscopic examinations after AGV implantation and/or TT.

Results:

In the AGVG, CEC density was reduced from 2247.0±527.3 to 1665.7±643.3 cells/mm2 (P<0.001). In the TAGVG, it was reduced from 2383.1±619.4 to 1552.9±700.9 cells/mm2 before TT (mean 41 mo of follow-up) and after TT, to 1394.6±654.7 cells/mm2 (mean 26 mo of the follow-up). The reduction rate of CEC density before TT was −12.2±6.5% per year, and this rate was significantly reduced to −3.5±6.9% per year after TT in the TAGVG (P=0.002). The probability of corneal failure defined as a 15% reduction in CEC density was significantly reduced after TT in TAGVG (P=0.038).

Conclusions:

Tube TT after AGV implantation markedly reduced the rate of CEC loss without serious complications in eyes with AGV implantation.
Surgical Outcomes of Visco-Circumferential-Suture-Trabeculotomy Versus Rigid Probe Trabeculotomy in Primary Congenital Glaucoma: A 3-Year Randomized Controlled Study
Authors: Elwehidy Ahmed S. , Bayoumi Nader H.L. , Abd Elfattah Dina , Hagras Sherein M.
Published: October 2021

Purpose:

The aim was to compare the long-term surgical outcomes of visco-circumferential-suture-trabeculotomy (VCST) and rigid probe viscotrabeculotomy (VT) in patients with primary congenital glaucoma (PCG).

Patients and Methods:

The study was conducted on 84 (47 right) eyes of 49 (32 males) children PCG to the pediatric ophthalmology unit of Mansoura Ophthalmic Center of Mansoura University, Egypt between 2015 and 2018. An initial office examination was followed by an examination under general anesthesia to establish the diagnosis of PCG. The children were then scheduled for surgery and the eyes randomly assigned to VCST or VT. Follow-up visits were scheduled at the first day, first week, first, and third months and then every 3 months for 1 year.

Results:

The mean±SD age of the study children at presentation was 4.8±2.1 and 4.9±1.7 months in the VCST and the VT groups, respectively (P=0.827). The mean±SD preoperative intraocular pressure (IOP) was 29.13±3.3 and 29.89±3.2 mm Hg in the VCST and VT groups, respectively (P=0.292) and 11.9±1.3 and 13.8±1.2 mm Hg at the end of 36 moths of follow-up (P<0.001). The IOP at all follow-up time points (except at the third month, P=0.924) was statistically significantly less in the VCST group than in the VT group (at week 1, month 1, 6, 9, 12, 18, 24, 30, and 36 the P<0.001). The cumulative probability of success was 100%, 95%, 90%, and 90%, respectively in VSCT and 100%, 72.7%, 97.7%, 90.9%, and 84% in VT at 12, 24, 30, and 36 months.

Conclusions:

Both VCST and VT were effective and safe for lowering the IOP in PCG with VCST providing a marginal advantage over VT.
Intraocular Pressure Control Following Phacoemulsification in Eyes With Pre-existing Aurolab Aqueous Drainage Implant
Authors: Wijesinghe Hiruni K. , Puthuran George V. , Ramulu Pradeep Y. , Ponnat Arvin K. , Reddy Madhan M. , Mani Iswarya , Krishnadas Subbaiah R. , Gedde Steven J.
Published: October 2021

Purpose:

The aim was to investigate intraocular pressure (IOP) control after phacoemulsification in adult glaucomatous eyes with a functioning nonvalved Aurolab Aqueous Drainage Implant (AADI) compared with eyes that did not have cataract extraction post-AADI.

Methods:

In this retrospective study, we reviewed records of 47 patients (47 eyes) who had a clear corneal phacoemulsification after AADI placement with a minimum of 2 years of follow up. The control group included 89 patients (89 eyes) who had a functional AADI at 1 year, minimum of 3 years of follow up post-AADI implantation, and no cataract extraction. The main outcome measure was failure (IOP >21 mm Hg or increased by >20% from prephacoemulsification level requiring at least 1 additional glaucoma medication, IOP ≤5 mm Hg, reoperation for glaucoma, or loss of light perception vision).

Results:

The median interval between AADI and phacoemulsification was 11.5 months (range: 4 to 68 mo), and the mean follow-up time after phacoemulsification was 35.6±6.4 months. The cumulative probability of failure was 14% (95% confidence interval=6%-31%) in the phaco group and 6% (95% confidence interval=3%-13%) in the control group at 2 years (P=0.11). Mean IOP was reduced from 16.5±4.5 mm Hg preoperatively to 15.4±4.7 mm Hg at 2 years after phacoemulsification (P=0.10). Mean LogMAR visual acuity improved from 1.1±0.6 preoperatively to 0.6±0.7 at 2 years after phacoemulsification (P<0.001).

Conclusions:

In eyes with a pre-existing AADI, phacoemulsification resulted in visual improvement without a significant rise in IOP or increased risk of AADI failure after 2 years follow up.
Blue Sclera as a Complication of Micropulse Transscleral Laser Therapy
Authors: Pandey Alka , Sanghi Shekhar , Chaudhary Sanjay
Published: October 2021

We report 3 patients who underwent micropulse laser therapy for glaucoma and subsequently developed a bluish-black discoloration of the sclera in a semicircular pattern corresponding to the probe path. This complication has not yet been reported with the micropulse laser treatment.
Twenty-Four-Month Outcome of Gonioscopy-Assisted Transluminal Trabeculotomy (GATT) in Eyes With Prior Corneal Transplant Surgery
Authors: Smith Oluwatosin U. , Butler Michelle R. , Grover Davinder S. , Kornmann Helen L. , Emanuel Matthew E. , Godfrey David G. , Fellman Ronald L. , Feuer William
Published: October 2021

Purpose:

Glaucoma is a well-known sequelae of corneal transplant surgery and is a leading cause of visual loss in this patient group. We evaluated the performance and safety of gonioscopy-assisted transluminal trabeculotomy (GATT) in this population.

Design:

Noncomparative retrospective case series.

Participants:

Consecutive eyes of patients receiving the GATT procedure for uncontrolled intraocular pressure (IOP) following corneal transplant surgery from 2016 to 2019.

Methods:

Retrospective analysis of eyes with a history of prior corneal transplant undergoing GATT at Glaucoma Associates of Texas between 2016 and 2019 was performed. Data included IOP, patient demographics, preoperative and postoperative medications, preoperative and postoperative corneal procedures, complications, and need for reoperation for IOP control.

Main Outcome Measures:

IOP reduction and medication use following the procedure.

Results:

Thirty-nine eyes of 32 patients with prior corneal transplant surgery underwent a GATT procedure. Prior corneal surgery included penetrating keratoplasty (59.0%), Descemet’s stripping endothelial keratoplasty (35.9%), Descemet’s membrane endothelial keratoplasty (2.6%), and deep anterior lamellar keratoplasty (2.6%). Patient age ranged from 24 to 94 years (mean 68.0 y) with 44% female and 81% Caucasian. The majority of patients had secondary open angle glaucoma (64.1%). There was a significant reduction in IOP and number of medications at all postoperative time points after censoring patients requiring reoperation to control IOP (P<0.001). At 24 months the pressure decreased from baseline of 30.9±11.5 to 13.9±4.7 mm Hg. Medications decreased from 4.2±1.0 medications at baseline to 0.6±1.0 at 24 months. Visual acuities decreased significantly over the first postsurgical month (all P<0.05), but these recovered at subsequent follow-up visits with 2-Snellen line improvements exceeding losses from month 3 to 36. Seven eyes required reoperation for uncontrolled glaucoma at a median of 8.5 months (range: 1.6 to 16.2 mo) after GATT. The cumulative proportion of eyes undergoing repeat cornea surgery was 2.6%, 2.6%, and 14.3% at 12, 24, and 36 months post-GATT, respectively.

Conclusions:

This case series describes a group of glaucoma patients, with a history of prior corneal surgery, that were safely and successfully treated with GATT. While classically traditional glaucoma surgeries are considered the standard of care for eyes following corneal transplant surgery, GATT should be considered as a reasonable, safe and effective alternative for surgically lowering IOP.
Three-Year Outcomes of Pars Plana Ahmed and Baerveldt Glaucoma Implantations for Neovascular Glaucoma in Japanese Eyes
Authors: Maeda Michiko , Ueki Mari , Sugiyama Tetsuya , Kohmoto Ryohsuke , Nemoto Emika , Kojima Shota , Ikeda Tsunehiko
Published: October 2021

Précis:

Tube shunt implantation through the pars plana was effective for neovascular glaucoma (NVG) for at least 3 years, with few serious postoperative complications observed.

Purpose:

The aim was to report 3-year outcomes of pars plana Ahmed and Baerveldt glaucoma implantation for NVG in Japanese eyes.

Patients and Methods:

This study examined 41 eyes of 39 patients who underwent tube shunt implantation through the pars plana with the Baerveldt glaucoma implant (BGI group, 26 eyes) or Ahmed glaucoma valve (AGV group, 15 eyes) for NVG and who were followed up for over 3 years at Osaka Medical College between January 2009 and April 2016. Outcome measures were intraocular pressure (IOP, mm Hg) at presurgery and at 6 months and 1, 2, and 3 years postoperative. Postoperative failure was defined as an IOP of >21 mm Hg or <5 mm Hg, further glaucoma surgery, or no light perception.

Results:

Mean IOPs at presurgery and at 3 years postoperative were 34.8±9.1 and 15.6±4.6 in the AGV group, and 36.9±9.2 and 12.8±5.5 in the BGI group. Mean antiglaucoma medication scores at 3 years postoperative were 1.3±1.4 in the AGV group and 0.4±0.8 in the BGI group (P=0.05). The number of eyes with a probability of failure at 6 months and at 2 and 3 years postoperative was 2, 3, and 4, respectively, in the BGI group, and 0, 1, and 2, respectively, in the AGV group.

Conclusion:

Findings for NVG cases showed tube shunt implantation through the pars plana was effective. Equivalent good IOP reductions were noted in both groups, with the BGI group requiring fewer postoperative antiglaucoma medications compared with the AGV group. Furthermore, both groups exhibited few serious postoperative complications.
Neonatal deaths among infants born to women living with HIV in the UK and Ireland
Authors: Yan Helen , Peters Helen , Thorne Claire
Published: October 2021

Objective(s):

To estimate the incidence of neonatal mortality among infants born to women living with HIV in the UK and Ireland in 1998–2017, describe causes of neonatal death (NND) and examine risk factors.

Design:

Population-based surveillance of pregnancies in diagnosed women living with HIV and their infants in the UK and Ireland.

Methods:

Estimated incidence of NND was reported for 1998–2017 and causes coded using the World Health Organization International Classification of Perinatal Mortality. Risk factor analyses used multivariable logistic regression, including delivery year, maternal origin, maternal age, delivery CD4+ cell count and viral load (VL), antiretroviral therapy (ART) at conception, preterm delivery (PTD), injecting drug use and infant sex.

Results:

There were 20 012 live-born infants delivered to 12 684 mothers in 19 601 pregnancies. The overall neonatal mortality rate was 4.10 per 1000 livebirths (95% confidence interval, 3.2–5.0), which was higher than that of the general population. Prematurity was the leading cause of death followed by congenital abnormality. Most NND occurred on the first day of life. ART at conception was associated with significantly reduced NND risk. In a restricted 2007–2017 analysis including VL, PTD and detectable maternal VL were associated with significantly increased NND risk.

Conclusions:

The vertical transmission rate in the UK, at 3 per 1000, is now lower than the neonatal mortality rate among infants born to women living with HIV. More research is needed to investigate the complex relationship between ART, preterm delivery and neonatal death in order to improve all perinatal outcomes.
Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc
Authors: Rose Ronald , Gartland Margaret , Li Zhufang , Zhou Nannan , Cockett Mark , Beloor Jagadish , Lataillade Max , Ackerman Peter , Krystal Mark
Published: October 2021

Background:

Temsavir (TMR), the active agent of the gp120-directed attachment inhibitor fostemsavir (FTR), the CD4-directed attachment inhibitor ibalizumab (IBA), and the CCR5 antagonist maraviroc (MVC) are antiretroviral agents that target steps in HIV-1 viral entry. Although mechanisms of inhibition of the three agents are different, it is important to understand whether there is potential for cross-resistance between these agents, as all involve interactions with gp120.

Methods:

Envelopes derived from plasma samples from participants in the BRIGHTE study who experienced protocol-derived virologic failure (PDVF) and were co-dosed with FTR and either IBA or MVC were analyzed for susceptibility to the agents. Also, CCR5-tropic MVC-resistant envelopes from the MOTIVATE trials were regenerated and studies were performed to understand whether susceptibility to multiple agents were linked.

Results:

The cloned envelopes exhibited reduced susceptibility to TMR and resistance to the co-dosed agent. At PDVF, emergent or preexisting amino acid substitutions were present at TMR positions of interest. When amino acid substitutions at these positions were reverted to the consensus sequence, full susceptibility to TMR was restored without effecting resistance to the co-dosed agent. In addition, five envelopes from MOTIVATE were regenerated and exhibited R5-tropic-MVC-resistance. Only one exhibited reduced susceptibility to TMR and it contained an M426L polymorphism. When reverted to 426M, full sensitivity for TMR was restored, but it remained MVC resistant.

Conclusion:

The data confirm that decreased susceptibility to TMR and resistance to IBA or MVC are not linked and that there is no cross-resistance between either of these two agents and FTR.
HIV-1 drug resistance and genetic diversity in a cohort of people with HIV-1 in Nigeria
Authors: Oluniyi Paul E. , Ajogbasile Fehintola V. , Zhou Shuntai , Fred-Akintunwa Iyanuoluwa , Polyak Christina S. , Ake Julie A. , Tovanabutra Sodsai , Iroezindu Michael , Rolland Morgane , Happi Christian T.
Published: October 2021

Objective:

This study was designed to provide information on the genetic diversity of HIV-1 and drug resistance mutations in Nigeria, as there is limited understanding of variants circulating in the country.

Methods:

We used an advanced next-generation sequencing platform, Primer ID, to: investigate the presence of high and low abundance drug resistance mutations; characterize preexisting Integrase Strand Transfer Inhibitor (INSTI) mutations in antiretroviral therapy (ART)-experienced but dolutegravir-naive individuals; detect recent HIV-1 infections and characterize subtype diversity from a cohort of people with HIV-1 (PWH).

Results:

HIV-1 subtype analysis revealed the predominance of CRF02_AG and subtype G in our study population. At detection sensitivity of 30% abundance, drug resistance mutations (DRMs) were identified in 3% of samples. At a sensitivity level of 10%, DRMs were identified in 27.3% of samples. We did not detect any major INSTI mutation associated with dolutegravir-resistance. Only one recent infection was detected in our study population.

Conclusion:

Our study suggests that dolutegravir-containing antiretroviral regimens will be effective in Nigeria. Our study also further emphasizes the high genetic diversity of HIV-1 in Nigeria and that CRF02_AG and subtype G are the dominant circulating forms of HIV-1 in Nigeria. These two circulating forms of the virus are largely driving the epidemic in the country.
Results of a cluster randomized trial testing the systems analysis and improvement approach to increase HIV testing in family planning clinics
Authors: Eastment McKenna C. , Wanje George , Richardson Barbra A. , Mwaringa Emily , Sherr Kenneth , Barnabas Ruanne V. , Perla Martha , Mandaliya Kishorchandra , Jaoko Walter , McClelland R. Scott
Published: October 2021

Objective:

The aim of this study was to test an implementation strategy, the Systems Analysis and Improvement Approach (SAIA), to increase rates of HIV testing and counseling (HTC) in family planning clinics in Mombasa, Kenya.

Design:

A cluster randomized trial.

Methods:

Twenty-four family planning clinics were randomized 1 : 1 to implementing SAIA versus usual procedures. Study staff implemented monthly SAIA cycles with family planning clinic staff for 12 months. SAIA has five steps. Step 1 uses a “cascade analysis’ tool to quantify the number of individuals who complete each step of a process. Step 2 involves sequential process flow mapping to identify modifiable bottlenecks in the system. Step 3 develops and implements workflow modifications to address bottlenecks. Step 4 assesses impact of the modification by recalculating the cascade analysis. Step 5 repeats the cycle. The primary outcome was the proportion of new family planning clients tested for HIV during the last quarter of the trial.

Results:

During the last 3 months of the trial, 85% (740/868) of new family planning clients were counseled for HIV in intervention clinics compared with 67% (1036/1542) in control clinics (prevalence rate ratio [PRR] 1.27, 95% confidence interval [CI] 1.15–1.30). Forty-two percent (364/859) of family planning clients were tested for HIV at intervention clinics compared with 32% (485/1521) at control clinics (PRR 1.33, 95% CI 1.16–1.52).

Conclusion:

SAIA led to a significant increase in HIV testing in family planning clinics in Mombasa. Integrating routine HTC into family planning clinics is a promising strategy to achieve the UNAIDS goal of 95% of people living with HIV being aware of their status.
Association Between Hyperlactatemia, Perfusional Parameters, and Lymphocyte Mitochondrial Dysfunction in Septic Shock Patients
Authors: Nedel Wagner Luis , Strogulski Nathan Ryzewski , Kopczynski Afonso , Rodolphi Marcelo Salimen , Montes Thiago Hermes Maeso , Júnior Jose Abruzzi , Friedman Gilberto , Portela Luis Valmor
Published: October 2021

Introduction:

In septic shock, mitochondrial dysfunction, and hypoperfusion are the main triggers of multi-organ failure. Little is known about the crosstalk between mitochondrial dysfunction and hemodynamic alterations, especially in the post-resuscitation phase. Here, we assess whether hypoperfusion and lactate levels are associated with oxygen consumption linked to mitochondrial bioenergetic activity in lymphocytes of patients admitted with septic shock.

Patients and Methods:

Prospective cohort study in patients with septic shock defined as the requirement of vasopressors to maintain a mean arterial pressure 65 mm Hg after initial fluid administration. Basal mitochondrial and Complex I respiration was measured to evaluate mitochondrial activity. Both variables and capillary refill time were compared with arterial lactate post-fluid resuscitation. We also compared mitochondrial activity measurements between patients with and without hypoperfusion status.

Results:

A total of 90 patients were included in analysis. The median arterial lactate at the time of septic shock diagnosis was 2.0 mmol/Dl (IQR 1.3–3.0). Baseline respiration at the time of septic shock diagnosis was correlated with lactate (Spearman −0.388, 95% CI −0.4893 to −0.1021; P = 0.003), as well as Complex I respiration (Spearman −0.403, 95% CI −0.567 to −0.208; P < 0.001). Patients with hypoperfusion status had no difference in basal respiration when compared with patients who did not have hypoperfusion status (P = 0.22) nor in Complex I respiration (P = 0.09).

Conclusion:

Changes in lymphocytic mitochondrial metabolism are associated with post-resuscitation arterial lactate in septic shock; however, they are not associated with the presence of a hypoperfusional status. In this scenario, it is therefore suggested that systemic perfusion and mitochondrial metabolism have different courses.
Plant Formulation ATRICOV 452 in Improving the Level of COVID-19 Specific Inflammatory Markers in Patients
Authors: Damle Latha , Damle Hrishikesh , Bharath BR
Published: October 2021

Due to the huge demand for health care facilities, there is a need for safe therapeutic intervention which can reduce the need for extensive health care support. In that regard, the current study was aimed at performing Phase 1 clinical trial to determine the safety of plant formulation in 24 healthy volunteers and Phase 2 trials in 100 COVID-19 patients to determine the tolerability and impact on the level of COVID 19 specific inflammatory markers. The outcomes of the Phase 1study have suggested the safe usage of plant formulation in humans and encouraged to conduct Phase 2 clinical trial. In the Phase 2 trial, the plant formulation was evaluated in 100 COVID-19 patients along with the standard of care. In Phase 1 single dose of 500 mg plant formulation capsule was used as an intervention, while 1gm thrice a day of plant formulation for 14 days was the testing dose for Phase 2. During the Phase 1 trial, no adverse event was observed and all organ systems were normal in function. During the Phase 2 trial, 100 patients underwent randomization, 50 were assigned to receive plant formulation, and 50 to receive placebo. Three patients in the placebo and two patients in the plant formulation group had dropped out from the study. Hence, the primary analysis population included 95 patients (48 allocated to plant formulation and 47 to placebo). The COVID 19 specific inflammatory markers improved faster and became normal in the plant formulation treatment group. In conclusion, the plant formulation (ATRICOV 452) has been found to be safe in phases 1 and 2.

Trial Registration

Phase 1: CTRI Registration number: CTRI/2020/09/027660

Phase 2: CTRI Registration number: CTRI/2021/01/030795
Metformin-mediated mitochondrial protection post-cardiac arrest improves EEG activity and confers neuroprotection and survival benefit
Authors: Shoaib Muhammad , Choudhary Rishabh C. , Chillale Rupesh K. , Kim Nancy , Miyara Santiago J. , Haque Shabirul , Yin Tai , Frankfurt Maya , Molmenti Ernesto P. , Zanos Stavros , Kim Junhwan , Becker Lance B.
Published: October 2021

Cardiac arrest (CA) produces global ischemia/reperfusion injury resulting in substantial multiorgan damage. There are limited efficacious therapies to save lives despite CA being such a lethal disease process. Surviving patients suffer extensive brain damage with mitochondrial dysfunction implicated as a major source of injury. Metformin, a first-line treatment for diabetes, has also shown promising results in other diseases and is known to interact with mitochondria. In the present study, we evaluated the therapeutic benefits of metformin administration immediately after resuscitation using a 10 min asphxyial-CA rat model. This is the first study to show that metformin treatment post-CA a) improves survival and neurologic function, b) potentiates early normalization of brain electrophysiologic activity, and c) protects mitochondrial function with a reduction in apoptotic brain injury. Overall, as an effective and safe drug, metformin has the potential to be an easily translatable intervention for improving survival and preventing brain damage after CA.

Brain damage post-cardiac arrest is a major cause of death; metformin protects brain mitochondria and improved survival and brain function.
A genome-wide epistatic network underlies the molecular architecture of continuous color variation of body extremities: a rabbit model
Authors: Demars Julie , Labrune Yann , Iannuccelli Nathalie , Deshayes Alice , Leroux Sophie , Gilbert Helene , Aymard Patrick , Benitez Florence , Riquet Juliette
Published: October 2021

Deciphering the molecular architecture of coat coloration for a better understanding of the biological mechanisms underlying pigmentation still remains a challenge. We took advantage of a rabbit French experimental population in which both a pattern and a gradient of coloration from white to brown segregated within the himalayan phenotype. The whole experimental design was genotyped using the high density Affymetrix® AxiomOrcun™ SNP Array and phenotyped into 6 different groups ordered from the lighter to the darker. Genome-wide association analyses pinpointed an oligogenic determinism, under recessive and additive inheritance, involving genes already known in melanogenesis (ASIP, KIT, MC1R, TYR), and likely processed pseudogenes linked to ribosomal function, RPS20 and RPS14. We also identified (i) gene-gene interactions through ASIP:MC1R affecting light cream/beige phenotypes while KIT:RPS responsible of dark chocolate/brown colors and (ii) a genome-wide epistatic network involving several others coloration genes such as POT1 or HPS5. Finally, we determined the recessive inheritance of the English spotting phenotype likely involving a copy number variation affecting at least the end of the coding sequence of the KIT gene. Our analyses of coloration as a continuous trait allowed us to go beyond much of the established knowledge through the detection of additional genes and gene-gene interactions that may contribute to the molecular architecture of the coloration phenotype. Moreover, the characterization of a network including genes that contribute to melanogenesis and pigmentation, two processes affected in various human disorders, shows the potential interest of our rabbit model for transversal studies.
Constrained optimisation of divisional load in hierarchically-organised tissues during homeostasis
Authors: Ashcroft Peter , Bonhoeffer Sebastian
Published: October 2021

It has been hypothesised that the structure of tissues and the hierarchy of differentiation from stem cell to terminally-differentiated cell play a significant role in reducing the incidence of cancer in that tissue. One specific mechanism by which this risk can be reduced is by minimising the number of divisions – and hence the mutational risk – that cells accumulate as they divide to maintain tissue homeostasis. Here we investigate a mathematical model of cell division in a hierarchical tissue, calculating and minimising the divisional load while constraining parameters such that homeostasis is maintained. We show that the minimal divisional load is achieved by binary division tress with progenitor cells incapable of selfrenewal. Contrary to the protection hypothesis, we find that an increased stem cell turnover can lead to lower divisional load. Furthermore, we find that the optimal tissue structure depends on the time horizon of the duration of homeostasis, with faster stem cell division favoured in short-lived organisms and more progenitor compartments favoured in longer-lived organisms.
Investigating lead removal at trace concentrations from water by inactive yeast cells
Authors: Stathatou Patritsia M. , Athanasiou Christos E. , Tsezos Marios , Goss John W. , Blackburn Camron , Tourlomousis Filippos , Mershin Andreas , Sheldon Brian W. , Padture Nitin P. , Darling Eric M. , Gao Huajian , Gershenfeld Neil
Published: October 2021

Traces of heavy metals found in water resources, due to mining activities and e-waste discharge, pose a global threat. Conventional treatment processes fail to remove toxic heavy metals, such as lead, from drinking water in a resource-efficient manner when their initial concentrations are low. Here, we show that by using the yeastSaccharomyces cerevisiaewe can effectively remove trace lead from waterviaa rapid mass transfer process, achieving an uptake of up to 12 mg lead per gram of biomass in solutions with initial lead concentrations below 1 part per million. We found that the yeast cell wall plays a crucial role in this process, with its mannoproteins and β-glucans being the key potential lead adsorbents. Furthermore, we discovered that biosorption is linked to a significant increase in cell wall stiffness. These findings open new opportunities for using environmentally friendly and abundant biomaterials for advanced water treatment targeting emerging contaminants.

One-Sentence Summary

Removing toxic heavy metals from water at challenging trace levels in an environmentally friendly, resource-efficient manner.
Antibiotic and novel compounds manipulation in vitro collagen matrix cells changes extracellular matrix non-complete cell division of fibroblast cells as new dermology technology
Authors: Ahmed Waseem , Azmat Rafia , Qayyum Abdul , Ahmed Rasheed , Moin Sumeira
Published: October 2021

Fibroblasts are several cells that are essential for human skin function and regulation process, the underfeed cells are a further issue of skin disorder the current study was based on isolated novel antibiotics compounds comparison of (Chloramphenicol IV) with the changes of Extracellular matrix (RC), inflammatory cells (SC) and non-complete cell division (ICD) effects on fibroblasts cell changes with the cell wall in structural and morphological changes. The new antibiotic compounds were measured and characters in (FTIR) methods with their functional group’s analysis of bioactive compounds from Adhatoda vasica and Calotropis procera plants and their effective inhibition concentrations (I C50) extract’s against tyrosinase conditions with their activity in vitro enzymatic process, both extracts have higher enzymatic inhibition assay was assessed. The fibroblast cells were compared with Chloramphenicol IV antibiotics with extracted compounds the cell wall was indiscretion and complete shape and structural changes were measured. The higher values of Diphenolase (22.5 μg/mL) was noted in Adhatoda vasica while an IC50 value of Monophenolase was 19.16 μg/mL, which is helpful in the treatment of fibroblast cell disorders, were higher in collagenase inhibition assay, elastase inhibition assay, hyaluronidase inhibition assay, tyrosinase inhibition assay process. It was concluded that novel antibiotics compounds from species could act an as effective role in fibroblast were used in future medicines as sources of locations and creams to control various skin diseases and skin disorder management’s processes.