Paradoxical herniation associated with hyperbaric oxygen therapy after decompressive craniectomy: A case report

BACKGROUND Whether hyperbaric oxygen therapy(HBOT)can cause paradoxical herniation is still unclear.CASE SUMMARY A 65-year-old patient who was comatose due to brain trauma underwent decompressive craniotomy and gradually regained consciousness after surgery.HBOT was administered 22 d after surgery due to speech impairment.Paradoxical herniation appeared on the second day after treatment,and the patient’s condition worsened after receiving mannitol treatment at the rehabilitation hospital.After timely skull repair,the paradoxical herniation was resolved,and the patient regained consciousness and had a good recovery as observed at the follow-up visit.CONCLUSION Paradoxical herniation is rare and may be caused by HBOT.However,the underlying mechanism is unknown,and the understanding of this phenomenon is insufficient.The use of mannitol may worsen this condition.Timely skull repair can treat paradoxical herniation and prevent serious complications.

Precisely Controlled Synthesis of Pt-Pd Octahedral Nanoframes as a Superior Catalyst towards Oxygen Reduction Reaction

Pt-based nanoframes represent a class of promising catalysts towards oxygen reduction reaction. Herein, we, for the first time, successfully prepared Pt-Pd octahedral nanoframes with ultrathin ridges less than 2 nm in thickness. The Pt-Pd octahedral nanoframes were obtained through site-selected deposition of Pt atoms onto the edge sites of Pd octahedral seeds, followed by selective removal of the Pd octahedral cores via chemical etching. Due to that a combination of three-dimensional opens geometrical structure and Pt-skin surface compositional structure, the Pt-Pd octahedral nanoframes/C catalyst shows a mass activity of 1.15 A/mgPt towards oxygen reduction reaction, 5.8 times enhancement in mass activity relative to commercial Pt/C catalyst （0.20 A/mgPt）. Moreover, even after 8000 cycles of accelerated durability test, the Pt-Pd octahedral nanoframes/C catalyst still exhibits a mass activity which is more than three times higher than that of pristine Pt/C catalyst.

Synergistic chemotherapy/PTT/oxygen enrichment by multifunctional liposomal polydopamine nanoparticles for rheumatoid arthritis treatment

Amultifunctional liposomal polydopamine nanoparticle(MPM@Lipo)was designed in this study,to combine chemotherapy,photothermal therapy(PTT)and oxygen enrichment to clear hyperproliferating inflammatory cells and improve the hypoxic microenvironment for rheumatoid arthritis(RA)treatment.MPM@Lipo significantly scavenged intracellular reactive oxygen species and relieved joint hypoxia,thus contributing to the repolarization of M1 macrophages into M2 phenotype.Furthermore,MPM@Lipo could accumulate at inflammatory joints,inhibit the production of inflammatory factors,and protect cartilage in vivo,effectively alleviating RA progression in a rat adjuvant-induced arthritis model.Moreover,upon laser irradiation,MPM@Lipo can elevate the temperature to not only significantly obliterate excessively proliferating inflammatory cells but also accelerate the production of methotrexate and oxygen,resulting in excellent RA treatment effects.Overall,the use of synergistic chemotherapy/PTT/oxygen enrichment therapy to treat RA is a powerful potential strategy.

Effectiveness of cognitive behavior therapy for sleep disturbance and glycemic control in persons with type 2 diabetes mellitus:A community-based randomized controlled trial in China

BACKGROUND Poor sleep quality is a common clinical feature in patients with type 2 diabetes mellitus(T2DM),and often negatively related with glycemic control.Cognitive behavioral therapy(CBT)may improve sleep quality and reduce blood sugar levels in patients with T2DM.However,it is not entirely clear whether CBT delivered by general practitioners is effective for poor sleep quality in T2DM patients in community settings.AIM To test the effect of CBT delivered by general practitioners in improving sleep quality and reducing glycemic levels in patients with T2DM in community.METHODS A cluster randomized controlled trial was conducted from September 2018 to October 2019 in communities of China.Overall 1033 persons with T2DM and poor sleep quality received CBT plus usual care or usual care.Glycosylated hemoglobin A1c(HbAlc)and sleep quality[Pittsburgh Sleep Quality Index(PSQI)]were assessed.Repeated measures analysis of variance and generalized linear mixed effects models were used to estimate the intervention effects on hemoglobin A1c and sleep quality.RESULTS The CBT group had 0.64,0.50,and 0.9 lower PSQI scores than the control group at 2 mo,6 mo,and 12 mo,respectively.The CBT group showed 0.17 and 0.43 lower HbAlc values than the control group at 6 mo and 12 mo.The intervention on meanΔHbAlc values was significant at 12 mo(t=3.68,P<0.01)and that meanΔPSQI scores were closely related toΔHbAlc values(t=7.02,P<0.01).Intentionto-treat analysis for primary and secondary outcomes showed identical results with completed samples.No adverse events were reported.CONCLUSION CBT delivered by general practitioners,as an effective and practical method,could reduce glycemic levels and improve sleep quality for patients with T2DM in community.

Neoadjuvant chemoradiotherapy for resectable esophageal cancer:an in-depth study of randomized controlled trials and literature review

Surgery following neoadjuvant chemoradiotherapy(NCRT) is a common multidisciplinary treatment for resectable esophageal cancer(EC). After analyzing 12 randomized controlled trials(RCTs), we discuss the key issues of surgery in the management of resectable EC. Along with chemoradiotherapy, NCRT is recommended for patients with squamous cell carcinoma(SCC) and adenocarcinoma(AC), and most chemotherapy regimens are based on cisplatin, fluorouracil(FU), or both(CF). However, taxane-based schedules or additional studies, together with newer chemotherapies, are warranted. In nine clinical trials, post-operative complications were similar without significant differences between two treatment groups. In-hospital mortality was significantly different in only 1 out of 10 trials. Half of the randomized trials that compare NCRT with surgery in EC demonstrate an increase in overall survival or disease-free survival. NCRT offers a great opportunity for margin negative resection, decreased disease stage, and improved loco-regional control. However, NCRT does not affect the quality of life when combined with esophagectomy. Future trials should focus on the identification of optimum regimens and selection of patients who are most likely to benefit from specific treatment options.

Prognosis of Connective Tissue Disease Related Interstitial Lung Disease after Initiation of Long-Term Oxygen Therapy: Comparison with Idiopathic Pulmonary Fibrosis

Objective: The studies of long-term oxygen therapy (LTOT) for patents with connective tissue disease-related interstitial lung disease (CTD-ILD) are limited. This study aimed to evaluate the prognosis of CTD-ILD patients following the initiation of LTOT, compared to those with idiopathic pulmonary fibrosis (IPF). Methods: We conducted a retrospective analysis of patients with CTD-ILD and IPF who were introduced to LTOT between January 2014 and December 2020. Results: The study included 24 patients with CTD-ILD and 55 patients with IPF. At the initiation of LTOT, female gender, never-smoking history, higher body mass index (BMI), higher lactate dehydrogenase (LDH) level, lower pulmonary Surfactant Protein-D (SP-D) level and lower Gender-Age-Physiology (GAP) scores were more common in the CTD-ILD group (all Conclusion: Although patients with CTD-ILD had longer overall survival than those with IPF, there was no significant difference in prognosis after the initiation of LTOT between the two groups. Early intervention including treatment and management will be needed in CTD-ILD as in IPF.

Normothermic regional perfusion mobile teams in controlled donation after circulatory death pathway: Evidence and peculiarities

To facilitate the implementation of controlled donation after circulatory death(cDCD)programs even in hospitals not equipped with a local Extracorporeal Membrane Oxygenation(ECMO)team(Spokes),some countries and Italian Regions have launched a local cDCD network with a ECMO mobile team who move from Hub hospitals to Spokes for normothermic regional perfusion(NRP)implantation in the setting of a cDCD pathway.While ECMO teams have been clearly defined by the Extracorporeal Life Support Organization,regarding composition,responsibilities and training programs,no clear,widely accepted indications are to date available for NRP teams.Although existing NRP mobile networks were developed due to the urgent need to increase the number of cDCDs,there is now the necessity for transplantation medicine to identify the peculiarities and responsibility of a NRP team for all those centers launching a cDCD pathway.Thus,in the present manuscript we summarized the character-istics of an ECMO mobile team,highlighting similarities and differences with the NRP mobile team.We also assessed existing evidence on NRP teams with the goal of identifying the characteristic and essential features of an NRP mobile team for a cDCD program,especially for those centers who are starting the program.Differences were identified between the mobile ECMO team and NRP mobile team.The common essential feature for both mobile teams is high skills and experience to reduce complications and,in the case of cDCD,to reduce the total warm ischemic time.Dedicated training programs should be developed for the launch of de novo NRP teams.

Generalized electro-biothermo-fluidic and dynamicalmodeling of cancer growth: state-feedback controlled cesium therapy approach

This paper develops a generalized dynamical model to describe the interactive dynamics between normal cells, tumor cells, immune cells, drug therapy, electromagnetic field of the human cells, extracellular heat and fluid transfer, and intercellular fractional mass of Oxygen, cell acidity and Pancreatin enzyme. The overall dynamics stability, controllability and observability have been investigated. Moreover, Cesium therapy is considered as a control input to the 11-dimensional dynamics using state-feedback controlled system and pole placement technique. This approach is found to be effective in driving the desired rate of tumor cell kill and converging the system to healthy equilibrium state. Furthermore, the ranges of the system dynamics parameters which lead to instability and growth of tumor cells have been identified. Finally, simulation results are demonstrated to verify the effectiveness of the applied approach which can be implemented successfully to cancer patients.

Prognostic factors for acute central retinal artery occlusion treated with hyperbaric oxygen:The Hong Kong study report number five

BACKGROUND Central retinal artery occlusion(CRAO)is a potentially blinding disease,and hyperbaric oxygen therapy(HBOT)is becoming increasingly popular with the support of scientific evidence.Despite the presence of various acute management measures,there is no clear evidence on the gold standard treatment for CRAO.AIM To identify factors and imaging parameters associated with good visual outcome,which guide ophthalmologists in the triage of CRAO patients for HBOT.METHODS Patients who suffered from CRAO and had a symptom onset≤6 h were recruited for a course of HBOT in a tertiary hospital after failing bedside treatment.Patient demographics,onset time,CRAO eye parameters,and past medical history were prospectively collected.Visual outcomes after HBOT were also analyzed.RESULTS A total of 26 patients were included;the female-to-male ratio was 1:1.6,and the mean age was 67.5 years±13.3 years(range 44–89 years).The mean duration of follow-up and mean visual acuity(VA)improvement were 10.0 mo±5.3 mo and 0.48 logarithm of minimal angle of resolution(logMAR)±0.57 logMAR(approx-imately 9 letters in ETDRS)(P=0.0001,Z=-3.67),respectively.The 1 mm zone of central macular thickness(CMT)on optical coherence tomography was not associated with VA changes(P=0.119);however,the 1-to-3 mm circular rim of CMT was fairly associated(P=0.02,Spearman's coefficient=0.45).Complete retinal perfusion time during fundus fluorescein angiography(FFA)was mode-rately associated(P=0.01,Spearman's coefficient=0.58)with visual outcome.

A multi-center randomized controlled clinical trial of three-step acupuncture and cupping therapy for cervicogenic headache

Objective:To assess the clinical efficacy and safety of three-step acupuncture and cupping therapy for cervicogenic headache(CEH).Methods:A randomized,single-blind,multi-center,parallel controlled clinical trial was performed,including 63 patients with CEH who met the study criteria.They were randomly divided into treatment(n=32)and control groups(n=31).The treatment group was treated with three-step acupuncture and cupping therapy,and the control group was treated with sham acupuncture.The simplified McGill pain scores,comprising three parts:the pain rating index,visual analogue scale score,and present pain intensity,alongside head and neck stiffness and cervical vertebra range of motion,and a safety evaluation were recorded in the two groups before treatment,immediately after the first treatment,after 10 days of treatment,after 20 days of treatment,and 3 months after the end of treatment.Results:Compared with before treatment,the scores at each follow-up time point were significantly improved after treatment;moreover,the treatment group was significantly better than the control group.When the scores at the 3 months follow-up after the end of the treatment were compared with the scores after 20 days of treatment,there were no significant differences in the treatment group while significant differences from the scores of the control group,suggesting that the treatment group had better long-term benefits than the control group.Conclusion:Compared with the sham acupuncture group,the three-step acupuncture and cupping method has a beneficial effect in the treatment of CEH.It provides rapid benefits,has better short-and long-term efficacy than sham acupuncture,and is associated with a low recurrence rate.

Short term acupressure therapy on weight-reduction in adolescence: A randomized controlled trial

Aim: Common treatment options for obesity include a reduced-calorie diet, increased physical activity, behavioral modification, pharmacotherapy, and surgery. Ear acupressure may also be an effective adjunct therapy. Methods: This study used a randomized controlled design to test the effectiveness of auricular acupressure for weight reduction in young, Taiwan Residents adults with a BMI ≥ 23 kg/m2. Sixty-eight participants aged 18 to 20 years were recruited from Taiwan Residents universities at the beginning of the study. After four weeks of auricular therapy, the total sample included 57 young adults. All participants met one time per week for ten minutes. The treatment group received ear acupressure treatment with Semen Vaccariae sticks on auricular acupoints while the control group had adhesive tape placed on ear acupoints, change in BMI from baseline to trial completion. Results: BMI in controls increased significantly by +0.0133 kg/m2 (P = 0.000) while the intervention group BMI decreased significantly by ?0.8022 kg/m2 (P ≤ 0.0001). Conclusions: Just four weeks of auricular acupressure by Semen Vaccariae, sticks may significantly help to decrease BMI among young adults.

Effect of Zangfu ointment and massage therapy on functional constipation:a protocol for a randomised controlled trial

Introduction:Functional Constipation(FC)is a type of functional bowel disease that is in Clinically characterized by dysportia,decreased frequency of bowel movements,or incomplete bowel movements in the absence of irritable bowel syndrome syndrome,at least 6 months before diagnosis,and symptoms within the last 3 months.At present,commonly used drugs include enema and suppositories,laxatives,microecological preparations,gastrointestinal motility drugs and other treatments.However,the effect is limited.Traditional Chinese medicine(TCM)treatment of FC has advantages.Methods:In this randomized controlled study,244 eligible patients were randomly assigned in a 1:1 ratio to a treatment group(Zangfu ointment and massage therapy+Lactulose Oral Liquid)and a control group(Lactulose Oral Liquid)for 14 days.Number of spontaneous defecation per week and First defecation time will be used as primary outcomes,and Traditional Chinese Medicine(TCM)syndrome scores and syndrome scores,PAC-QOL form will be used as secondary outcomes.Blood routine,liver function,and renal function will be used as safety outcomes.The primary and secondary outcomes will be performed at 0th,7th,and 14th day,and the safety outcomes will be performed at 0th and 14th day.Ethics and dissemination:Ethical approval has been obtained from the Committee on Health Research Ethics of the Fangshan Hospital,Beijing University of Chinese Medicine,Beijing,People's Republic of China(FZY LK-2020-010)on September 18,2020.All patients will be provided oral and written information about the trial before screening.The study results will be disseminated by peer-review publications and conference presentations.Trial registration number:ChiCTR2000038754(registered on April 14,2021).This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial license,which permits others to distribute,remix,adapt,build upon this work non-commercially,and license their derivative works on different terms,provided the original work is properly cited,appropriate credit is given,any changes made indicated,and the use is non-commercial.STRENGTHS AND LIMITATIONS OF THIS STUDY(1)The efficacy of the Zangfu ointment and massage therapy is evaluated in a randomised,double-blind 2-week clinical trial in FC patients.(2)Form a complete and generalizable regimen for the treatment of FC(Qi stagnation)with the Zangfu ointment and massage therapy.

Incisional Negative Pressure Wound Therapy in the Prevention of Surgical Site Infection after Vascular Surgery with Inguinal Incisions: Rationale and Design of a Randomized Controlled Trial (INVIPS-Trial)

Background/Aims: Inguinal incisions are a common route of access in vascular surgery. Due to anatomical challenges and a diverse bacterial flora in this area, surgical site infections (SSI) represent a common, debilitating and sometimes life-threatening complication. The INVIPS-Trial evaluates the role of Negative Pressure Wound Therapy (NPWT) on closed inguinal incisions in elective vascular surgery to prevent SSI and other wound complications. Methods: This randomized controlled trial (RCT) registered at ClinicalTrials.gov (Identifier: NCT01913132) compares the effects of a NPWT dressing (PICO, Smith & Nephew, UK) and the center’s standard wound dressing (Vitri Pad, ViTri Medical, Sweden) on postoperative wound complications, especially SSI. The study includes two distinct vascular procedures with different SSI risk profiles: endovascular aortic repair (EVAR) and open surgical approaches involving the common femoral artery (OPEN). Results: Four hundred ninety-five groin incisions in both treatment arms are anticipated to be included in the EVAR group and 147 inguinal incisions in both treatment arms in the OPEN group. Since a large percentage of inguinal vascular procedures in both groups but especially in the EVAR group are performed bilaterally, many patients can serve as their own control by randomly receiving NPWT on one and the standard dressing on the contralateral inguinal incision. Conclusions: This ongoing RCT attempts to elucidate the potential benefit of NPWT on closed inguinal incisions after different vascular procedures. Outcome and conclusions of this trial could have implications on postoperative wound care of patients in both vascular surgery and other surgical specialties.

Taxol Production in Suspension Cultures of Taxus chinensis as Affected by the Combination of Nutrient Feed with Dissolved Oxygen Control

Influence of the combination of nutrient feed with dissolved oxygen control on taxol production in suspension cultures of Taxus chinensis (Pilg.) Rehd. was investigated in bioreactors. Addition of feeding medium with 20 g/L sucrose on day 16 enhanced both the biomass and taxol production in 5-L bioreactors. Further investigation of the fed-batch cultures in a 20-L bioreactor showed that cultivation under a low dissolved oxygen tension (DOT) of 20% for the entire culture resulted in the highest taxol content of 0.98 mg/g DW, while the taxol production was lower than that with 40% and 60% DOT. Moreover, taxol accumulation was remarkably improved by the cultivation of cells initially under DOT of 60% for 20 d followed by changing the DOT to 20% for another 12 d. By combining the use of these two strategies, a maximum taxol content of 18.7 mg/L was obtained in a 20-L bioreactor.

A randomized controlled clinical trial on the treatment of Thymosin-a1 versus interferon-α in patients with hepatitis B

INTRODUCTIONChronic hepatitis B virus (HBV) infection is a serious problem because of its world wide distribution and possible adverse sequelae ,such as cirrhosis and hepatocellular carcinoma .The World Health Organization estimates that HBV has infected mord than 350 million people worldwide ,and up to 20% of them will become chromic carricrs and will be at significant risk for cirrhosis and HCC .The ultimate goal of the therapy for chronic hepatitis B is to prevent progression to cirrhosis and to prevent development of HCC.

Assessment of knowledge, attitude and practice regarding oxygen therapy at emergency departments in Riyadh in 2017: A cross-sectional study

BACKGROUND: Administering oxygen therapy(OT) has an essential role in preventing/managing hypoxemia in both acute and chronic conditions. It should be adjusted to achieve the normal oxygen saturation of 94%–98% in most cases. This study aims to evaluate knowledge, attitude and practice(KAP) of nurses, paramedics, emergency medical technicians(EMTs) and Emergency Medical Services(EMS) physicians working at emergency departments(ED) in Riyadh, Saudi Arabia. METHODS: In this cross-sectional study, a structured questionnaire was used to assess KAP related to OT of nurses, paramedics, EMTs and EMS physicians currently working at an ED of a tertiary care hospital. Knowledge and attitude were assessed using a Likert scale from 1–5, whereas practice was assessed as a yes/no categorical variable.RESULTS: A total of 444 emergency health-care workers(EHCWs) participated, of which 225(50.7%) were male, with the majority(77%) in the age group of 20–35 years. Over half of the sample were nurses(266; 59.9%). The mean score for knowledge about OT was 5.51±1.45, attitude was 26.31±3.17 and for practices 4.55±1.76. The main factors which were associated with poor KAP were workload and lack of local guidelines. The distribution of overall practice score was signifi cantly better among paramedics – nurses group and EMT – nurses group.CONCLUSION: This study demonstrates that there is a gap in EHCWs' KAP, particularly regarding when to provide OT to a patient. This gap can affect patients' safety. Extensive educational and training programs about OT are needed to raise awareness among health-care providers.

Hyperbaric oxygen therapy combined with Schwann cell transplantation promotes spinal cord injury recovery

Schwann cell transplantation and hyperbaric oxygen therapy each promote recovery from spinal cord injury, but it remains unclear whether their combination improves therapeutic results more than monotherapy. To investigate this, we used Schwann cell transplantation via the tail vein, hyperbaric oxygen therapy, or their combination, in rat models of spinal cord contusion injury. The combined treatment was more effective in improving hindlimb motor function than either treatment alone; injured spinal tissue showed a greater number of neurite-like structures in the injured spinal tissue, somatosensory and motor evoked potential latencies were notably shorter, and their amplitudes greater, after combination therapy than after monotherapy. These findings indicate that Schwann cell transplantation combined with hyperbaric oxygen therapy is more effective than either treatment alone in promoting the recovery of spinal cord in rats after injury.

Hyperbaric oxygen therapy as a complementary treatment for radiation proctitis:Useless or useful?-A literature review

Radiotherapy(RT)is the backbone of multimodality treatment of more than half of cancer cases.Despite new modern RT techniques,late complications may occur such as radiation proctitis(RP).The natural history of RP is unpredictable.Minor symptoms may resolve spontaneously or require conservative treatment.On the other hand,for similar and uncomplicated clinical contexts,symptoms may persist and can even be refractory to the progressive increase in treatment measures.Over the last decades,an enormous therapeutic armamentarium has been considered in RP,including hyperbaric oxygen therapy(HBOT).Currently,the evidence regarding the impact of HBOT on RP and its benefits is conflicting.Additional prospective and randomised studies are necessary to validate HBOT’s effectiveness in the‘real world’clinical practice.This article reviewed the relevant literature on pathophysiology,clinical presentation,different classifications and discuss RP management including a proposal for a therapeutic algorithm with a focus on HBOT.

SINGLET OXYGEN QUANTUM YIELDS OF PORPHYRIN-BASED PHOTOSENSITIZERS FOR PHOTODYNAMIC THERAPY

The major cytotoxic agent with most current photosensitizers used in photodynamic therapy(PDT)is widely believed to be singlet oxygen(^(1)O_(2)).Determination of the ^(1)O_(2) quantum yields for porphyrin-based photosensitizers,including hematoporphyrin derivative(HiPorfin),hematoporphyrin monomethyl ether(HMME)and photocarcinorin(PsD-007)in air-saturated dimethylformamide(DMF)solutions were performed by the direct measurement of their near-infrared luminescence.In addition,^(1)O_(2) quencher sodium azide was employed to confirm the ^(1)O_(2) generation from the investigated photosensitizers.The maximal ^(1)O_(2) luminescence occurs at about 1280 nm with full width at half maximum of 30 nm.The ^(1)O_(2) quantum yields were found to be 0.61±0.03,0.60±0.02 and 0.59±0.03 for HiPorfin,HMME and PsD-007,respectively.These results provide that these porphyrin-based photosensitizers produce ^(1)O_(2) under irradiation,which is of significance for the study of their photodynamic action in PDT.

The neuroprotective effects of oxygen therapy in Alzheimer’s disease:a narrative review

Alzheimer’s disease(AD)is a degenerative neurological disease that primarily affects the elderly.Drug therapy is the main strategy for AD treatment,but current treatments suffer from poor efficacy and a number of side effects.Non-drug therapy is attracting more attention and may be a better strategy for treatment of AD.Hypoxia is one of the important factors that contribute to the pathogenesis of AD.Multiple cellular processes synergistically promote hypoxia,including aging,hypertension,diabetes,hypoxia/obstructive sleep apnea,obesity,and traumatic brain injury.Increasing evidence has shown that hypoxia may affect multiple pathological aspects of AD,such as amyloid-beta metabolism,tau phosphorylation,autophagy,neuroinflammation,oxidative stress,endoplasmic reticulum stress,and mitochondrial and synaptic dysfunction.Treatments targeting hypoxia may delay or mitigate the progression of AD.Numerous studies have shown that oxygen therapy could improve the risk factors and clinical symptoms of AD.Increasing evidence also suggests that oxygen therapy may improve many pathological aspects of AD including amyloid-beta metabolism,tau phosphorylation,neuroinflammation,neuronal apoptosis,oxidative stress,neurotrophic factors,mitochondrial function,cerebral blood volume,and protein synthesis.In this review,we summarized the effects of oxygen therapy on AD pathogenesis and the mechanisms underlying these alterations.We expect that this review can benefit future clinical applications and therapy strategies on oxygen therapy for AD.