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Article: Male histone deacetylase 6 (HDAC6) knockout mice have enhanced ventilatory responses to hypoxic challenge.

Getsy, Paulina M / Coffee, Gregory A / Kelley, Thomas J / Lewis, Stephen J

2024 Volume 14, Page(s) 1332810

Abstract: Histone deacetylase 6 (HDAC6) is a class II histone deacetylase that is predominantly localized in the cytoplasm of cells. HDAC6 associates with microtubules and regulates acetylation of tubulin and other proteins. The possibility that HDAC6 participates ...

Abstract	Histone deacetylase 6 (HDAC6) is a class II histone deacetylase that is predominantly localized in the cytoplasm of cells. HDAC6 associates with microtubules and regulates acetylation of tubulin and other proteins. The possibility that HDAC6 participates in hypoxic signaling is supported by evidence that 1) hypoxic gas challenges cause microtubule depolymerization, 2) expression of hypoxia inducible factor alpha (HIF-1α) is regulated by microtubule alterations in response to hypoxia, and 3) inhibition of HDAC6 prevents HIF-1α expression and protects tissue from hypoxic/ischemic insults. The aim of this study was to address whether the absence of HDAC6 alters ventilatory responses during and/or after hypoxic gas challenge (10% O
Language	English
Publishing date	2024-02-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2023.1332810
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Article: Loss of ganglioglomerular nerve input to the carotid body impacts the hypoxic ventilatory response in freely-moving rats.

Getsy, Paulina M / Coffee, Gregory A / Lewis, Stephen J

Frontiers in physiology

2023 Volume 14, Page(s) 1007043

Abstract: The carotid bodies are the primary sensors of blood pH, ... ...

Abstract	The carotid bodies are the primary sensors of blood pH, pO
Language	English
Publishing date	2023-03-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2023.1007043
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Article ; Online: Recognition of posterior thoracolumbar instrumentations used in spinal deformity surgery and techniques for implant removal.

Kato, So / Lewis, Stephen J

Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia

2021 Volume 86, Page(s) 217–222

Abstract: Spinal surgeries requiring implant removals/revisions are becoming more common, as a long time has passed since contemporary spinal instrumentation was developed and utilized. Recognizing implants and manufacturers preoperatively from radiographs and ... ...

Abstract	Spinal surgeries requiring implant removals/revisions are becoming more common, as a long time has passed since contemporary spinal instrumentation was developed and utilized. Recognizing implants and manufacturers preoperatively from radiographs and preparing appropriate instruments for removal are mandatory. The objective of the present paper was to review the various designs of contemporary posterior thoracolumbar spinal implants along with their radiographic features to facilitate the identification of previously used systems in removal or revision surgeries. We focused on contemporary spinal implants that have been commonly used in spinal deformity surgery since the development of screw-and-rod constructs up to 2005. The pertinent information was requested from three major manufacturers (DePuy Synthes, Medtronic and Stryker). Characteristics of each system are reviewed with radiographic features, and the instruments needed for revision are summarized. We propose a systematic identification diagram. Rod loading can be categorized as offset-loading, side-loading or top-loading. Screw design can be cylindrical, conical or dual-core threading. Each system has unique features that can facilitate identification. Identifying the materials and diameters of the rod is also imperative. When removal of an unidentified system is needed or removal of an identified system fails, the short rod has to remain loaded on the screw and the implant removed en bloc as an isolated piece. Understanding the radiographic features of spinal implants used in previous surgeries will help surgeons prepare for the increasing incidence of revision surgeries.
MeSH term(s)	Bone Screws ; Device Removal/methods ; Female ; Humans ; Internal Fixators ; Lumbar Vertebrae/diagnostic imaging ; Lumbar Vertebrae/surgery ; Male ; Neurosurgical Procedures/instrumentation ; Neurosurgical Procedures/methods ; Retrospective Studies ; Spinal Diseases/diagnostic imaging ; Spinal Diseases/surgery ; Spinal Fusion/instrumentation ; Spinal Fusion/methods ; Thoracic Vertebrae/diagnostic imaging ; Thoracic Vertebrae/surgery
Language	English
Publishing date	2021-02-10
Publishing country	Scotland
Document type	Journal Article ; Review
ZDB-ID	1193674-5
ISSN	1532-2653 ; 0967-5868
ISSN (online)	1532-2653
ISSN	0967-5868
DOI	10.1016/j.jocn.2021.01.045
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Zs.A 3999: Show issues

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Article ; Online: Post-operative bracing following adult spine deformity surgery: Results from the AO Spine surveillance of post-operative management of patients with adult spine deformity.

Kato, So / Smith, Justin S / Driesman, Devin / Shaffrey, Christopher I / Lenke, Lawrence G / Lewis, Stephen J

PloS one

2024 Volume 19, Issue 4, Page(s) e0297541

Abstract: Study design: Cross-sectional international survey with a literature review.: Objectives: While some surgeons favor spine bracing after surgery for adult spine deformity (ASD) to help prevent mechanical failures, there is a lack of evidence. The ... ...

Abstract	Study design: Cross-sectional international survey with a literature review. Objectives: While some surgeons favor spine bracing after surgery for adult spine deformity (ASD) to help prevent mechanical failures, there is a lack of evidence. The objective of the present study was to better understand the current trend in the use of bracing following ASD surgery based on an international survey. Methods: An e-mail-based online survey was conducted among over 6000 international AO Spine members regarding the post-operative management of patients with ASD. The details of brace prescription, indications and influencing factors were solicited. Descriptive data were summarized based on different demographic groups and fusion levels for the responding surgeons who annually perform at least 10 long-segment fusions of >5 levels extending to the pelvis. Results: A total of 116 responses were received, including 71 surgeons (61%) who used post-operative bracing for >5 levels of long fusion. The most common reason for bracing was pain management (55%) and bone quality was the strongest influencing factor (69%). Asia-Pacific surgeons had the highest rate of bracing (88%), while North American surgeons had the lowest (45%). The most common type of brace used were TLSO for cases with an uppermost instrumented vertebra (UIV) in the low- or mid-thoracic spine and a cervical brace for UIV at T1-3. The majority (56%) used bracing for 6-12 weeks after surgery. Conclusions: The present survey demonstrated significant interest in bracing following ASD surgery, however, there is substantial variability in post-operative bracing practice. A formal study on the role of bracing in ASD surgery is needed.
MeSH term(s)	Adult ; Humans ; Cross-Sectional Studies ; Spine/surgery ; Braces ; Orthotic Devices ; Surveys and Questionnaires ; Spinal Fusion/methods ; Retrospective Studies
Language	English
Publishing date	2024-04-16
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0297541
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Article: Male histone deacetylase 6 (HDAC6) knockout mice have enhanced ventilatory responses to hypoxic challenge.

Getsy, Paulina M / Coffee, Gregory A / Kelley, Thomas J / Lewis, Stephen J

Research square

2023

Abstract: Histone deacetylase 6 (HDAC6) is a class II histone deacetylase that is predominantly localized in the cytoplasm of cells. HDAC6 associates with microtubules, regulating acetylation of tubulin and other proteins. The possibility that HDAC6 participates ... ...

Abstract	Histone deacetylase 6 (HDAC6) is a class II histone deacetylase that is predominantly localized in the cytoplasm of cells. HDAC6 associates with microtubules, regulating acetylation of tubulin and other proteins. The possibility that HDAC6 participates in hypoxic signaling is supported by evidence that (1) hypoxic gas challenges cause microtubule depolymerization, (2) expression of hypoxia inducible factor alpha (HIF)-1α is regulated by microtubule alterations in response to hypoxia, and (3) inhibition of HDAC6 prevents HIF-1α expression and protects tissue from hypoxic/ischemic insults. The aim of this study was to address whether the absence of HDAC6 alters ventilatory responses during and/or after hypoxic gas challenges (10% O
Language	English
Publishing date	2023-06-13
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3005686/v1
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Article ; Online: Advances in D-Amino Acids in Neurological Research.

Seckler, James M / Lewis, Stephen J

International journal of molecular sciences

2020 Volume 21, Issue 19

Abstract: D-amino acids have been known to exist in the human brain for nearly 40 years, and they continue to be a field of active study to today. This review article aims to give a concise overview of the recent advances in D-amino acid research as they relate to ...

Abstract	D-amino acids have been known to exist in the human brain for nearly 40 years, and they continue to be a field of active study to today. This review article aims to give a concise overview of the recent advances in D-amino acid research as they relate to the brain and neurological disorders. This work has largely been focused on modulation of the N-methyl-D-aspartate (NMDA) receptor and its relationship to Alzheimer's disease and Schizophrenia, but there has been a wealth of novel research which has elucidated a novel role for several D-amino acids in altering brain chemistry in a neuroprotective manner. D-amino acids which have no currently known activity in the brain but which have active derivatives will also be reviewed.
MeSH term(s)	Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amino Acids/metabolism ; Brain/metabolism ; Brain/pathology ; Brain Chemistry ; Humans ; N-Methylaspartate/genetics ; N-Methylaspartate/metabolism ; Receptors, N-Methyl-D-Aspartate/genetics ; Receptors, N-Methyl-D-Aspartate/metabolism ; Schizophrenia/metabolism ; Schizophrenia/pathology
Chemical Substances	Amino Acids ; Receptors, N-Methyl-D-Aspartate ; N-Methylaspartate (6384-92-5)
Language	English
Publishing date	2020-10-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21197325
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Article ; Online: The effect of post-discharge oral nutritional supplements on outcomes after gastrointestinal surgery: A systematic review and meta-analysis

Rowley, Annabel / Adiamah, Alfred / Kushairi, Anisa / Lewis, Stephen J. / Lobo, Dileep N.

Clinical Nutrition. 2023 May 05,

2023

Abstract: Malnutrition is a risk-factor for adverse postoperative outcomes. This systematic review and meta-analysis evaluated the impact of post-discharge oral nutritional supplements (ONS) on outcomes in patients undergoing gastrointestinal surgery. The Medline ... ...

Abstract	Malnutrition is a risk-factor for adverse postoperative outcomes. This systematic review and meta-analysis evaluated the impact of post-discharge oral nutritional supplements (ONS) on outcomes in patients undergoing gastrointestinal surgery. The Medline and Embase databases were searched for randomised clinical trials in patients undergoing gastrointestinal surgery who had received ONS for at least two weeks after discharge from hospital. The primary endpoint was weight change. Secondary endpoints included quality of life, total lymphocyte count, total serum protein and serum albumin. Analysis was performed using RevMan5.4 software. Fourteen studies with 2480 participants (1249 ONS/1231 controls) were included. Pooling of results revealed that a reduction in postoperative weight loss in patients taking ONS, when compared with control: overall weighted mean difference (WMD) −1.69 kg, 95% CI −2.98 to −0.41, P = 0.01. Serum albumin concentration was increased in the ONS group: WMD = 1.06 g/L, 95% CI 0.04 to 2.07, P = 0.04. Haemoglobin was also increased: WMD = 2.91 g/L, 95% CI 0.58 to 5.25, P = 0.01. Total serum protein, total lymphocyte count, total cholesterol and quality of life did not differ between the groups. Patient compliance was relatively poor across the studies and there was variability in the composition of ONS, volume consumed and surgical procedures performed. There was a reduction in postoperative weight loss and an improvement in some biochemical parameters in patients receiving ONS after gastrointestinal surgery. Future RCTs with more consistent methodologies are needed to investigate the efficacy of ONS after discharge from hospital following gastrointestinal surgery.
Keywords	cholesterol ; clinical nutrition ; computer software ; gastrointestinal system ; hemoglobin ; hospitals ; lymphocyte count ; malnutrition ; meta-analysis ; patient compliance ; quality of life ; serum albumin ; surgery ; systematic review ; weight loss ; Post-discharge nutrition ; Oral nutritional supplements ; Postoperative outcomes ; Gastrointestinal surgery ; BWL ; CI ; EORTC ; ESPEN ; NICE ; ONS ; PRISMA ; RCT ; SI ; WMD
Language	English
Dates of publication	2023-0505
Publishing place	Elsevier Ltd
Document type	Article ; Online
Note	Pre-press version ; Use and reproduction
ZDB-ID	604812-2
ISSN	1532-1983 ; 0261-5614
ISSN (online)	1532-1983
ISSN	0261-5614
DOI	10.1016/j.clnu.2023.04.028
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 1774: Show issues

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Article ; Online: Surveying nonvisual arrestins reveals allosteric interactions between functional sites.

Seckler, James M / Robinson, Emily N / Lewis, Stephen J / Grossfield, Alan

Proteins

2022 Volume 91, Issue 1, Page(s) 99–107

Abstract: Arrestins are important scaffolding proteins that are expressed in all vertebrate animals. They regulate cell-signaling events upon binding to active G-protein coupled receptors (GPCR) and trigger endocytosis of active GPCRs. While many of the functional ...

Abstract	Arrestins are important scaffolding proteins that are expressed in all vertebrate animals. They regulate cell-signaling events upon binding to active G-protein coupled receptors (GPCR) and trigger endocytosis of active GPCRs. While many of the functional sites on arrestins have been characterized, the question of how these sites interact is unanswered. We used anisotropic network modeling (ANM) together with our covariance compliment techniques to survey all the available structures of the nonvisual arrestins to map how structural changes and protein-binding affect their structural dynamics. We found that activation and clathrin binding have a marked effect on arrestin dynamics, and that these dynamics changes are localized to a small number of distant functional sites. These sites include α-helix 1, the lariat loop, nuclear localization domain, and the C-domain β-sheets on the C-loop side. Our techniques suggest that clathrin binding and/or GPCR activation of arrestin perturb the dynamics of these sites independent of structural changes.
MeSH term(s)	Animals ; Arrestins/metabolism ; beta-Arrestins/metabolism ; Arrestin/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Clathrin/metabolism
Chemical Substances	Arrestins ; beta-Arrestins ; Arrestin ; Receptors, G-Protein-Coupled ; Clathrin
Language	English
Publishing date	2022-08-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	806683-8
ISSN	1097-0134 ; 0887-3585
ISSN (online)	1097-0134
ISSN	0887-3585
DOI	10.1002/prot.26413
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Zs.A 2291: Show issues

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Article: Clinical Efficacy and Safety of Controlled Distraction-Compression Technique Using Expandable Titanium Cage in Correction of Posttraumatic Kyphosis.

Kang, Dongho / Lewis, Stephen J / Kim, Dong-Hwan

Journal of Korean Neurosurgical Society

2021 Volume 65, Issue 1, Page(s) 84–95

Abstract: Objective: To investigate the clinical efficacy and safety of the controlled distraction-compression technique using an expandable titanium cage (ETC) in posttraumatic kyphosis (PTK).: Methods: We retrospectively studied and collected data on 20 ... ...

Abstract	Objective: To investigate the clinical efficacy and safety of the controlled distraction-compression technique using an expandable titanium cage (ETC) in posttraumatic kyphosis (PTK). Methods: We retrospectively studied and collected data on 20 patients with PTK. From January 2014 to December 2017, the controlled distraction-compression technique using ETC was consecutively performed in 20 patients with PTK of the thoracolumbar zone (range, 36-82 years). Among them, nine were males and 11 were females and the mean age was 61.5 years. The patients were followed regularly at 1, 3, 6, and 12 months, and the last follow-up was more than 2 years after surgery. Results: The mean follow-up period was 27.3±7.3 months (range, 14-48). The average operation time was 286.8±33.1 minutes (range, 225-365). The preoperative regional kyphotic angle (RKA) ranged from 35.6° to 70.6° with an average of 47.5°±8.1°. The immediate postoperative mean RKA was 5.9°±3.8° (86.2% correction rate, p=0.000), and at the last follow-up more than 2 years later, the mean RKA was 9.2°±4.9° (80.2% correction rate, p=0.000). The preoperative mean thoracolumbar kyphosis was 49.1°±9.2° and was corrected to an average of 8.8°±5.3° immediately after surgery (p=0.000). At the last follow-up, a correction of 11.9°±6.3° was obtained (p=0.000). The preoperative mean back visual analog scale (VAS) score was 7.9±0.8 and at the last follow-up, the VAS score was improved to a mean of 2.3±1.0 with a 70.9% correction rate (p=0.000). The preoperative mean Oswestry disability index (ODI) score was 32.3±6.9 (64.6%) and the last follow-up ODI score was improved to a mean of 6.85±2.9 (3.7%) with a 78.8% correction rate (p=0.000). The overall complication was 15%, with two of distal junctional fractures and one of proximal junctional kyphosis and screw loosening. However, there were no complications directly related to the operation. Conclusion: Posterior vertebral column resection through the controlled distraction-compression technique using ETC showed safe and good results in terms of complications, and clinical and radiologic outcomes in PTK. However, to further evaluate the efficacy of this surgical procedure, more patients need long-term follow-up and there is a need to apply it to other diseases.
Language	English
Publishing date	2021-11-15
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2253817-3
ISSN	1598-7876 ; 2005-3711 ; 1225-8245
ISSN (online)	1598-7876
ISSN	2005-3711 ; 1225-8245
DOI	10.3340/jkns.2021.0147
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Article: Fentanyl activates opposing opioid and non-opioid receptor systems that control breathing.

Baby, Santhosh M / May, Walter J / Getsy, Paulina M / Coffee, Gregory A / Nakashe, Tej / Bates, James N / Levine, Alan / Lewis, Stephen J

Frontiers in pharmacology

2024 Volume 15, Page(s) 1381073

Abstract: Fentanyl elicits profound disturbances in ventilatory control processes in humans and experimental animals. The traditional viewpoint with respect to fentanyl-induced respiratory depression is that once the effects on the frequency of breathing (Freq), ... ...

Abstract	Fentanyl elicits profound disturbances in ventilatory control processes in humans and experimental animals. The traditional viewpoint with respect to fentanyl-induced respiratory depression is that once the effects on the frequency of breathing (Freq), tidal volume (TV), and minute ventilation (MV = Freq × TV) are resolved, then depression of breathing is no longer a concern. The results of the present study challenge this concept with findings, as they reveal that while the apparent inhibitory effects of fentanyl (75 μg/kg, IV) on Freq, TV, and MV in adult male rats were fully resolved within 15 min, many other fentanyl-induced responses were in full effect, including opposing effects on respiratory timing parameters. For example, although the effects on Freq were resolved at 15 min, inspiratory duration (Ti) and end inspiratory pause (EIP) were elevated, whereas expiratory duration (Te) and end expiratory pause (EEP) were diminished. Since the effects of fentanyl on TV had subsided fully at 15 min, it would be expected that the administration of an opioid receptor (OR) antagonist would have minimal effects if the effects of fentanyl on this and other parameters had resolved. We now report that the intravenous injection of a 1.0 mg/kg dose of the peripherally restricted OR antagonist, methyl-naloxone (naloxone methiodide, NLXmi), did not elicit arousal but elicited some relatively minor changes in Freq, TV, MV, Te, and EEP but pronounced changes in Ti and EIP. In contrast, the injection of a 2.5 mg/kg dose of NLXmi elicited pronounced arousal and dramatic changes in many variables, including Freq, TV, and MV, which were not associated with increases in non-apneic breathing events such as apneas. The two compelling conclusions from this study are as follows: 1) the blockade of central ORs produced by the 2.5 mg/kg dose of NLXmi elicits pronounced increases in Freq, TV, and MV in rats in which the effects of fentanyl had apparently resolved, and 2) it is apparent that fentanyl had induced the activation of two systems with counter-balancing effects on Freq and TV: one being an opioid receptor inhibitory system and the other being a non-OR excitatory system.
Language	English
Publishing date	2024-04-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2024.1381073
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