At present, androgen deprivation therapy (ADT) is still the standard regimen for patients with metastatic and locally advanced prostate cancer (PCa). The level of androgen receptor splice variant-7 (AR-V7) in men with castration-resistant prostate cancer (CRPC) has been reported to be elevated compared with that in patients diagnosed with hormone-sensitive prostate cancer (HSPC).Herein, we performed a systematic review and cumulative analysis to evaluate whether the expression of AR-V7 was significantly higher in patients with CRPC than in HSPC patients.The commonly used databases were searched to identify the potential studies reporting the level of AR-V7 in CRPC and HSPC patients. The association between CRPC and the positive expression of AR-V7 was pooled by using the relative risk (RR) with the corresponding 95% confidence intervals (CIs) under a random-effects model. For detecting the potential bias and the heterogeneity of the included studies, sensitivity analysis and subgroup analysis were performed. Publication bias was assessed Egger’s and Begg’s tests. This study was registered on PROSPERO (ID: CRD42022297014).p < 0.001). In the sensitivity analysis, the combined RRs did not change substantially, ranging from 6.85  to 9.84 . In the subgroup analysis, a stronger association was detected in RNA in situ hybridization (RISH) measurement in American patients, and those studies were published before 2011 . There was no significant publication bias identified in our study.This cumulative analysis included 672 participants from seven clinical trials. The study group contained 354 CRPC patients, while the other group contained 318 HSPC patients. Pooled results from the seven eligible studies showed that the expression of positive AR-V7 was significantly higher in men with CRPC compared to those with HSPC (RR = 7.55, 95% CI: 4.61–12.35, Evidence from the seven eligible studies demonstrated that patients with CRPC had a significantly elevated positive expression of AR-V7. More investigations are still warranted to clarify the association between CRPC and AR-V7 testing.https://www.crd.york.ac.uk/prospero/, identifier CRD42022297014. According to the data from Cancer Statistics 2022, prostate cancer (PCa) is the most frequently diagnosed male cancer in Western countries , 2. MoreThe current evidence suggests that CRPC may be not independent of the effect of androgen, but AR signaling continues to be essential . The resAR-V7 has been identified as one of the leading splice variants in both localized and advanced PCa . AR-V7 iSince a number of studies have identified the potential relationship between CRPC and AR-V7, it is clinically meaningful to summarize the evidence on this issue by conducting a meta-analysis. In this study, we performed a cumulative study to summarize and analyze the evidence on the association between CRPC and the AR-V7 expression.The current cumulative analysis was conducted according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) , which wThe Medline, Cochrane Library, and Embase were searched for systematic literature reviews. The time frame for searching the eligible studies was up to April 2022. Searches were conducted by using the subject headings and keywords. The following search terms were used: ((((((“Prostatic Neoplasms”[Mesh]) OR (Prostate Cancer)) OR (Prostatic Cancer)) AND ((((AR-V7) OR AR3) OR receptor splicing variant 7) OR androgen receptor 3))) AND castration-resistant prostate cancer). Moreover, we further reviewed the reference lists of the relevant articles to detect more eligible studies. Participants and the language of the search were restricted to American patients and English, respectively.in situ hybridization (ISH), PCR, and protein analysis.Clinical trials in which AR-V7 was investigated by any of the existing instruments were considered to be eligible. These included immunohistochemical (IHC) staining analysis, RNA in vitro experiments.Study eligibility was fully determined by the PICOS criteria, namely, the patient population, intervention or exposure, comparison, and outcome (PICOS) study design. The inclusion criteria included the following: 1) participants: men with prostate cancer PCa. 2) Interventions: CRPC. 3) Comparisons: HSPC. 4) Outcomes: the positive expression of AR. 5) Study design: any study designs. Furthermore, additional studies included in this review were supposed to provide the relative risk (RR) estimates with the corresponding 95% confidence intervals (CIs). A list of exclusion criteria was provided, as follows: 1) no control data; 2) updated or duplicated data; 3) review articles; 4) meeting abstract, commentaries, editorials, congress reports, letters, or case reports; and 5) animal or According to the predetermined selection criteria, two authors independently extracted the data. Data were obtained from the included studies, as follows: names of the first author, study design, publication year, study areas, the sample sizes of the study group and the control group, methods of AR-V7 detection, and the effect measures  with their 95% CI. The quality of cross-sectional studies was assessed by using the quality methodology checklist . The Newp-values <0.05 were defined as statistically significant. Heterogeneity across studies was determined by using the I2 statistic and Cochran’s Q statistic . Otherwise, a random-effects model was applied. Moreover, an analysis of sensitivity was conducted by omitting one study at one time to assess how it affected the overall risk estimate. The origins of heterogeneity were further examined by subgroup analyses. Publication biases were determined by using Begg’s and Egger’s tests .The strength of the association between CRPC and AR expression was assessed by the pooled RRs and 95% CIs. Results with tatistic . Fixed-e’s tests , 31. p >A diagram of the study selection process is shown in The characteristics of eligible publications are listed in I2 = 20.6%, p = 0.272); thus, the fixed-effects model was conducted to pool the data. As displayed in p < 0.001), which showed that CRPC was strongly correlated with an increased positive expression of AR-V7.No significant statistical heterogeneity was detected among all the eligible studies (p < 0.001) to 9.84  after eliminating any one of the included studies  group  compared with the IHC group  and PCR and protein analysis group . Moreover, in the subgroup analysis according to the geographical region, a statistically significant association between CRPC and positive expression of AR-V7 could be observed in the UK, the USA, and China, with RR (95% CIs) of 9.29 , 10.09 , and 5.30 , respectively. However, a similar association was not identified in Sweden . Finally, when further stratified by publication years 2009–2011 and 2012–2017, the RR of CRPC associated with positive AR-V7 expression was 8.00  and 7.34 , respectively.To further obtain the potential relationship between CRPC and the positive expression of AR-V7, subgroup analyses were performed according to the methods of AR-V7 detection, the geographical region, and the publication year Table 3.p > |z| = 0.133; Egger, p > |t| = 0.069)  5.p < 0.001). Based on the sensitivity analyses, the positive association between CRPC and AR-V7 remained significant in nearly all of the included studies.Recently, numerous studies , 37 had A majority of tumors eventually progress to CRPC after a period of an initial response to the ADT regimen . The undvs. 3.7 months; p < 0.001), shorter clinical progression-free survival , and shorter overall survival . Moreover, Todenhöfer et al.  and median overall survival  in CRPC patients treated with abiraterone. This association was confirmed in another clinical study that demonstrated that patients with positive expression of AR-V7 had a poor prognosis than those with negative AR-V7 expression in CRPC treatment with either enzalutamide or abiraterone ) to CRPC is the existence of AR splice variants. AR-V1 was the most common AR-V in hormone-naïve PCa, while AR-V7 was the most common during ADT and in the CRPC stage . HoweverIn addition to distinct demographic characteristics , different disease states, and the diverse treatments of CRPC or CSPC, it should be known that various detection methods and measurements for assessing the AR-V7 might also play a role in the outcomes among different studies. For example, Li and colleagues  showed tThe relationship between AR-V7 and CRPC has been extensively investigated, but whether AR-V7 itself or the ratio of full-length (FL) AR and AR-V7 plays a key role in CRPC remains to be resolved. It is common for patients with CRPC to co-express the full-length receptor and spliced variant AR-V7 . After hHowever, it was reported that AR-V7 could activate target genes irrespective of AR-FL, leading to the development and growth of prostate cancer under low androgen levels . AR-V7 aOur study is a high-quality cumulative analysis that was conducted following the PRISMA statement. However, some non-negligible limitations should be acknowledged when interpreting the outcomes derived from this study. First, heterogeneity was unavoidable among different studies, even though the potential causes of heterogeneity were identified by sensitivity analysis and subgroup analyses. The effects of small sample studies might be problematic in these meta-analyses, which resulted in the exaggeration of the summary estimates. Second, the various methods of assessment for AR-V7 among studies might also be one of the limitations of this study. Different kinds of assessments for AR-V7 may have a huge impact on the pooled analysis. Therefore, diverse measurements for detecting the AR-V7 expression might be another source of heterogeneity.Our study demonstrated that the positive expression of AR-V7 was significantly higher in patients with CRPC than that in those with HSPC. To improve clinical prognostic, the level of AR-V7 should be evaluated when clinicians determined the preferred treatments for CRPC. However, the present evidence was based on retrospective clinical trials with limited included studies. Therefore, further high-quality, large sample size and multicenter cohort studies are still warranted to validate our findings. At present, the predictive effects of the AR-V7 expression in CSPC/HSPC are controversial among studies, and this needs to be addressed in the near future.The original contributions presented in the study are included in the article/ShaZ: project development and manuscript writing. JL and MS: data collection. XL: data analysis. LZ and ShiZ: manuscript editing. All authors contributed to the article and approved the submitted version.


The Rubinstein alternating-offers bargaining game is reconsidered, where players show fairness concerns and their fairness references are characterized by the Nash bargaining solution. The objective of this paper is to explore the impact of fairness concerns in the alternating-offer bargaining game. Alternating-offer bargaining with fairness concerns is developed. We construct a subgame perfect equilibrium and show its uniqueness. Then, it is shown that players’ payoffs in the subgame perfect equilibrium are positively related to their own fairness concern coefficient and bargaining power and negatively to the opponents’ fairness concern coefficient. Moreover, it is shown that the limited equilibrium partition depends on the ratio of discount rates of the two players when the time lapse between two offers goes to zero. Finally, the proposed model is applied to the bilateral monopoly market of professional basketball players, and some properties of equilibrium price are shown. Our result provides the implication that players should carefully weigh their own fairness concerns, bargaining power and fairness concerns of their opponents, and then make proposals, rather than simply follow the suggestion that the proposal at the current stage is higher than that at the past stages. Bargaining plays an important role in economics. This is partly since bargaining between and among firms and individuals has an effect on many aspects of economic activity and partly because bargaining occupies a critical place in economic theory. Bargaining is the case of economic interaction where the market only plays a role in setting the bounds of discussion, and the bargaining outcomes are determined by the strategic interaction of the players. In particular, sufficient information about bargaining, including the attributes of the players and the structure of the bargaining problem faced by the players, allows the range of indeterminacy to be narrowed or eliminated . On the Different from the Nash bargaining model  that tries to predict the equilibrium solution to the negotiation issue, Rubinstein’s bargaining, as a strategic approach, exactly describes the negotiation process in detail . In the Although Rubinstein’s bargaining is convenient analytically, the utility specification in this model cannot explain fully the behavior preferences that are typically observed in some real bargaining situations. Thus, numerous scholars consider Rubinstein’s bargaining with behavior preferences, such as loss aversion ,9,10, riTo avoid latent misunderstandings, it is stressed that fairness is not outright altruism. An altruistic player may prefer to give away some payoff of himself or herself to another one. It is not necessarily case for a player with fairness preferences. A player with fairness preferences may in general be more prone to a higher payoff, even though this payoff difference would be obtained by other players ,22. For Although different fairness models are proposed by researchers ,19,21, tHowever, the significance of fairness preferences has received relatively little attention in the bargaining problem, with the exception of bargaining experiments ,27,28,29Without loss of generality, a player’s bargaining power is given exogenously. That is, it is assumed that players settle with their relative positions given. For instance, the bargaining power of the union can be determined by price-cost margins, wage premia, level of employment and revenue of the Belgian industry . In factIn this paper, we adopt the fairness model introduced by Du et al.  to charaOur work makes the following several contributions. Firstly, from the theoretical perspective, the present study contributes to the alternating-offer bargaining game literature by investigating players’ fairness preferences. This differs from Ewerhart  and KohlThe rest of this paper is organized as follows. Two players, 1 and 2, bargain over one unit of a pie. The set of all feasible divisions is denoted byt ∈ T: = {Δ, 2Δ,…}, where Δ > 0. Player 1 makes an offer z =  ∈ Z to player 2 at time t ∈ Todd: = {Δ, 3Δ,…}. If player 2 accepts this offer (Y), then the bargaining ends and player i  obtains the share iz. If player 2 rejects this offer (N), then player 2 makes a counteroffer to player 1 at time t + 1 ∈ Teven: = {2Δ, 4Δ,…}. If this offer is accepted, then the bargaining ends. If player 1 rejects this offer (N), then player 1 makes another proposal to player 2 at t + 2 ∈ Todd: = {Δ, 3Δ,…}, and so on. If the bargaining continues forever, then the share of each player is zero.Proposals are made at times δ < 1. Following the prior works , let, letδ < sistency . To addrsistency .t ∈ T, where sz ∈ Z for all s ≤ t. Let th of the bargaining game at time t ∈ T. Let F, which is the set of all sequences of functions of f =t = 1: tf ∈Z, for t > 1 and t ∈ oddT, tf: tH −1→ Z and for t ∈ evenT, tf: tH→ {Y, N}. Similarly, let G denote the set of strategies of player 2, in other words, G is the set of all sequences of functions of g =t ∈ oddT, tg: tH → {Y, N} and for t ∈ evenT, tg: tH−1 → Z.Let t is accepted, then an agreement path is denoted by , where sz ∈ Z for all s ≤ t. The set of all time t agreement paths is denoted by tA:={|th ∈ tH }. Let A: = tT∈tA, then it contains all agreement paths. Similarly, a disagreement path is denoted by , which means that the bargaining ends in breakdown at time t. We define tD: = {|th ∈ tH } and D: = tT∈tD. Finally, we define H∞: = {|tz ∈ Z for all t ∈ T}, which implies that the element of ∞D is referred to as infinite paths.If an offer at time f, g) can determine a play of the bargaining game. Specifically, if it leads to an agreement on a proposal at time t, then the set of paths contains t−1 paths in D and one path in A. If it leads to perpetual disagreement, then the set of paths only contains a single path in ∞H.Note that (iτ: A (or D) → , which reflects the share of the pie player i obtains in each finite path A (or D). Thus, for all th ∈ tH, we have iτ =iτ  = 0, where i’s share at time t.We define a function iλ (iλ > 0) is used to characterize the sensitivity to this gap. Specifically, both players bargain over a pie, whose size is π . For a fairness-concerned player i, the utility is shown as follows.iλ > 0 is the fairness concern coefficient of player i. iπ and ia are the realized material payoff and the proportion to the overall pie of player i, respectively, while ir are player i’s absolute fairness reference and relative fairness references, respectively. A fairness model was first introduced by Rabin . Howeveriλ (iλ > 0). That is, Du et al. argued that the fairness concern parameter iλ captures the sensitivity to the gap between the gain and the fairness reference when the gain is less than the fairness reference.Since the relative fairness reference implies a fair proportion regardless of the size of the pie, we restrict ourselves to the relative fairness reference that is more persuasive. In this fairness model, the fairness reference implies that a player would not pursue self-interest without considering the opponent’s welfare. On the other hand, gain below the farness reference reduces the utility and the sensitivity to this gap is characterized by the fairness concern parameter i’s inherent properties can be characterized by the fairness concern coefficient iλ that does not depend on player i’s bargaining power. On the other hand, the fairness concern coefficient iλ can be used to characterize the fairness concern level of player i.This fairness model characterizes fairness concerns. The player Since the relative fairness reference implies a fair proportion regardless of the size of the pie, we restrict ourselves to the relative fairness reference.Theorem 1.The relative fairness reference points of players 1 and 2 satisfy, respectivelywhere α reflects the bargaining power of player 1 and 1 − α reflects the bargaining power of player 2.Proof. i, we focus on player i’s utility per unit pie. By Nash’s axiomatic definition )All prior results can also be applied to this more general model. A solution to the above-mentioned two equalities is obtained from which a strategy profile is constructed. The strategy profile is the unique SPE that satisfies properties (i)−(ii). The outcome isCorollary 1.In the alternating-offers bargaining game with fairness concerns, if the time interval between two consecutive offers tends to zero, i.e., Δ→0, the outcome of the game converges toProof. These complete the proof of Corollary 1. □β1/β2.Note that the equilibrium partition for Δ→0 is critically influenced by the players’ discount rates. The player’s equilibrium payoff depends on the ratio The above sections refer to the alternating-offer bargaining model between two players. From now on, we focus on the application of the proposed bargaining model in a market with a single buyer and a single seller. To illustrate the validity of our bargaining model, the professional basketball market in North America is considered. In the professional basketball market, the National Basketball Association (NBA) monopolizes professional basketball games in America, while the National Basketball Players Association (NBPA) monopolizes the professional player market. Thus, the NBA can only employ professional basketball players from the NBPA, that is, the professional basketball market can be regarded as a bilateral monopoly market with a single buyer  and a single seller . In this market, the NBA and the NBPA bargain over players’ salaries and quantity. If an agreement cannot be reached, then the NBA seasons, including the NBA regular season, the NBA preceding season, the NBA playoffs and the NBA finals, may be delayed or canceled.q professional basketball players from the NBPA and benefit from these professional basketball players by playing basketball in the NBA season. Let R(q) denote by the revenue that is obtained by the NBA, and R(0) = 0, R′(q) > 0 and R″(q) < 0. Let C(q) be the NBPA ’s cost of provide q professional basketball players, and C(0) = 0,C′(q) > 0 and C″(q) > 0. Let R′(0) > C′(0). If the NBA decides to employ q professional basketball playersat a unit price p, then the NBA’s payoff function isThe NBA can employ Thus, the total surplus isq and the salary p according to the alternating-offers procedure. The bargaining begins with an offer by the NBA. It is assumed that the NBA and the NBPA pay attention to fairness. Let α be denoted by the NBA’s bargaining power, then 1−α reflects the NBPA’s bargaining power. The fairness reference is the Nash bargaining solution. Let br and sr denote by the fairness reference points of the NBA and the NBPA, respectively. It follows from Theorem 1 thatp, q), where p ≥ 0 and q ≥ 0. If the two players reach an agreement on  at time t, then the NBA’s utility function isThe NBA and the NBPA bargain over the quantity On the other hand, if the agreement cannot be reached forever, then the utility of each player is zero.Let ((eq is the unique solution toIt means thatSince Combining Equations (19) and (20), we haveSimilarly, we have(This means thatSince Combining Equations (20)–(24), we can obtainIt follows from Equations (13), (15), (20) and (25) that a player’s salary isSimilarly, it follows from Equations (14), (15), (19) and (26) that a player’s salary isBy straightforwardly adapting the proof of Theorem 2, it is shown that . That is, the NBA possesses 510 active players. Adam Silver, who is the NBA commissioner, reported that the total revenue of the NBA is about $ 10 billion in the 2021–2022 season . Consider the case that the number of players  for each team is at most 15 in the NBA season. This implies that the average revenue for active players is approximately equal to $ 27.8 million, that is, http://www.guangdonglong.com/c/0G5HA2H022.html, accessed on 21 July 2022). This implies that the average operation cost for each active player is $ 11.8 million, i.e., δ = 0.7, α = 0.3 and sλ = 2, we examine the impact of fairness concern parameters bλ on the salary, as shown in The NBA possesses 30 teams, each of which consists of 17 active players  if a player cares more fairness, this player should make a high proposal when it is his turn to make proposals. (2) A player should make a low proposal if its opponent cares more about fairness. (3) A player with strong bargaining power should make a high proposal. To summarize, players should carefully weigh their own fairness concerns, bargaining power and fairness concerns of their opponents, and then make proposals, rather than simply follow the suggestion that the proposal at the current stage is higher than that at the past stages.In this paper, the effect of fairness concerns on the Rubinstein (1982) alternating-offers bargaining game is investigated. We construct a SPE in the alternating-offers bargaining game with fairness concerns and show its uniqueness. A sensitivity analysis on the equilibrium partition with respect to fairness concern coefficients is performed, we further find that the player’s equilibrium share of the pie is positively related to the fairness concerns of this player and negatively to the opponent’s fairness concern. It is shown that the payoff of each player depends on the ratio of discount rates of the two players if the time lapse between two offers goes to zero. Finally, an application to bilateral monopoly is given and the properties of equilibrium price are shown.One limitation of this work is that players’ preferences are time-independent in Rubinstein’s bargaining game with fairness concerns. In numerous situations, this assumption is reasonable, while in others this assumption is often violated and players’ payoffs depend on the process of bargaining. Thus, the objective of future study is to discuss the effect of fairness concerns on the alternating-offers bargaining game with history-dependent preferences. In addition, the SPE is unique that shares two properties  with that of Rubinstein. It still is an open issue whether the uniqueness is also held without the above-mentioned two properties.


Quality of life (QoL) is essential for maintaining a healthy, balanced lifestyle, especially among individuals with chronic diseases. Saudi Arabia (SA) launched a health sector transformation program as part of the nationwide Vision 2030 initiative to ensure the sustainable development of efficient healthcare services, aiming to improve health by increasing well-being and QoL. More investigation into the current status of health rehabilitation services provided to individuals with chronic diseases and future needs to optimize services and improve QoL is needed. This was narratively discussed by experts from different health rehabilitation services in SA. Comprehensive health rehabilitation services including orthopedic, occupational, cardiac, pulmonary, critical care, perioperative, hearing and speech, substance use disorders, and vocational rehabilitation services were addressed. Health rehabilitation services in SA, as in other countries, are suboptimal for individuals in health rehabilitation programs. To optimize the QoL of individuals with chronic diseases, health rehabilitation services should be tailored based on the unique requirements of each service and its serving patients. The shared need to improve health rehabilitation services includes the adoption of home-based and telehealth services, the integration of multi-governmental sectors, the empowerment and allocation of health rehabilitation specialists, public awareness campaigns, policy legislation and guideline development, and the implementation of a long-term follow-up system. This review is one of the first to address the intersection of health rehabilitation services and QoL in SA; urgent and holistic actions are paramount to address the pressing need to optimize SA’s health rehabilitation services. The experts’ recommendations in this study may be applicable to other countries’ health systems, as health rehabilitation services are not well optimized globally. Living a healthy, balanced lifestyle is essential for promoting a high quality of life (QoL) , particuLong-term conditions are the leading causes of morbidity and mortality worldwide. SA is not an exception, as the most important factors causing disability in the country are cancer, diabetes, cardiopulmonary diseases, injuries from road traffic accidents, and mental illness ,5. TheseThe ability to perform ADLs can be considered when evaluating QoL . EarlierThe prevalence and longevity of individual disabilities are increasing due to population growth, aging, and medical advancements that protect and increase longevity . These fThe purpose of this review is to highlight the current status of health rehabilitation services provided in SA and to identify the future needs to improve the services that intersect with QoL. This study was conducted by experts specializing in different health rehabilitation fields, including orthopedic, occupational, cardiac, pulmonary, critical care, perioperative, hearing and speech, substance use disorder, vocational rehabilitation, and healthcare services, to comprehensively assess the health rehabilitation services provided in SA. Ultimately, this review will assist policymakers, clinicians, and researchers in perceiving the current status and future needs of health rehabilitation services in the country to meet the nation’s 2030 vision for optimizing QoL. In addition, the experts’ recommendations in this study can be applied to the global context, as health rehabilitation services are not well optimized globally.Orthopedic rehabilitation is a professional practice that focuses on returning individuals to function and reversing their trajectory of disability. Rapid changes in orthopedic rehabilitation to accommodate the effective and efficient management of patients with musculoskeletal (MSK) conditions have been implemented. Orthopedic rehabilitation services can include a multidisciplinary team of physical and occupational therapists to provide efficient and relatively specialized rehabilitation. Orthopedic rehabilitation in SA is an efficient system that operates under the government of the Ministry of Health, which manages over 494 hospitals and 2300 primary healthcare centers . AccordiIn SA, musculoskeletal conditions are escalating rapidly, ranking in the top three potential reasons to visit the hospital and accounting for 38% of family practice visits . The resFour dimensional factors that have an association with QoL include MSK pain, physical function, mental health, and the self-perception of health . The quaAssessing QoL in orthopedic physical therapy is essential for evaluating patient well-being and intervention efficacy. The major limitation of the QoL measurement is a lack of sensitivity; therefore, a patient-centered QoL measurement can be established to address all the factors that impact recovery and perception of care. Furthermore, despite the widespread provision of orthopedic physical therapy for movement-related impairment, few studies have focused on the optimal parameters for exercise interventions designed to improve QoL. Therefore, it is essential to understand the current status of HR-QoL, which requires identifying the optimal exercise training parameters to optimize HR-QoL. Additionally, the predisposing risk factors for musculoskeletal disabilities require the imperative action of orthopedic physical therapy stockholders to enhance social awareness of physical activity and initiate health initiatives that will improve physical activity in the country. Furthermore, orthopedic physical therapy has become an area of considerable interest in most health rehabilitation centers in SA, particularly in secondary and tertiary health care. However, the availability of physical therapy services in primary healthcare centers must be evaluated to meet the growing health needs of the Saudi population, especially among individuals residing in rural areas.Occupational therapy is a professional practice in healthcare that applies the therapeutic use of individuals’ daily life occupations to improve occupational performance and participation . The scoOccupational rehabilitation services play a major role in improving the QoL of clients. Since the beginning of the occupational therapy profession, a link has been established between occupational rehabilitation and QoL. Occupational rehabilitation services have been shown to improve QoL by increasing ADLs, instrumental activities of daily living (IADLs), and community participation among individuals with occupational issues ,26. MultOccupational rehabilitation services are the key to the NCDBD initiative . HoweverDespite advanced and evolving interventions in medicine, cardiovascular disease is the global leading cause of mortality . In SA, Randomized controlled trials have shown strong evidence regarding the cost-effectiveness and benefits of cardiac rehabilitation. However, access to cardiac rehabilitation programs is poor . In SA, There is a clear need to increase the number of cardiac rehabilitation programs in SA, as well as the number of personnel needed to run such programs. An awareness of the benefits of cardiac rehabilitation is warranted to motivate people with chronic heart disease to take up training and increase program retention. Furthermore, there is a need to increase individual referrals by cardiologists to cardiac rehabilitation programs and implement a long-term follow-up, which necessitates a comprehensive initiative by stakeholders to ease the enrollment and monitoring of program outcomes. All these factors are expected to increase lifespan and improve QoL among individuals with chronic cardiovascular disease.Pulmonary rehabilitation is an interdisciplinary program that is mostly run by pulmonologists, physiotherapists, and respiratory therapists for patients with chronic pulmonary diseases such as chronic obstructive pulmonary disease (COPD), interstitial lung diseases, bronchiectasis, asthma, and scoliosis. It is individually tailored and designed to improve an individual’s physical and social performance by delivering exercise and educational sessions to people with chronic respiratory diseases . AccordiDespite the benefits of pulmonary rehabilitation , the uptAlthough the government has made great efforts to invest in the healthcare system, the number of pulmonary rehabilitation programs is limited . A recenThere are various barriers to establishing efficient pulmonary rehabilitation programs in SA, including a lack of national guidelines to standardize the services, a lack of qualified and trained personnel, and hospital capacity . MoreoveTackling such obstacles to improving pulmonary rehabilitation uptake is imperative. One suggested strategy is telepulmonary rehabilitation using digital technology, which has been shown to have equal efficacy to center-based pulmonary rehabilitation . This apGenerally, ICU critical illnesses are clinical syndromes and are heterogeneous by nature, thus making the reliability of critical illness epidemiological data unavailable and challenging to obtain. Acute respiratory distress syndrome, sepsis, and acute kidney injury are examples of critical illnesses that are treated in the ICU ,65. The Nevertheless, evidence-based practice has shown that the impact of long-term ICU impairments can be mitigated by interdisciplinary rehabilitation during the ICU stay and after discharge . ImplemeRecognizing the status of ICU rehabilitation is important for improving the services provided to ICU survivors in each country . In SA, The mortality rate alone is no longer sufficient to successfully determine the quality of ICU outcomes. Moreover, the magnitude of long-term ICU impairments is increasingly recognized, especially after the COVID-19 pandemic and subsequent global surge in ICU admissions. Hospitals in SA should develop ICU rehabilitation provisions to address the current issues of QoL and functional outcomes in ICU survivors. While a lack of awareness and the consequent proper training for providing critical care rehabilitation are global challenges, Saudi hospitals are no exception. Closing the gap in awareness and knowledge in highlighting the necessity for patients to undergo rehabilitation protocols from the first day of ICU admission is a major challenge to driving ICU culture change. Although there are many other barriers facing ICU rehabilitation, such as staffing, finances, adequate space, and equipment, upholding ICU rehabilitation as a priority would accelerate the momentum towards achieving this mission.ICUs should prioritize the application of the ABCDEF bundle policy. Effective pain and delirium management, proper use of sedation and analgesia, the application of early mobility and mechanical ventilation, spontaneous weaning trials, and family engagement should be part of ICU daily routine care. The involvement of psychological and social contexts from specialized psychology specialists, social workers, and other ICU practitioners places a greater emphasis on individual patients and their families. This holistic approach to ICU care would provide the foundation for humanizing ICUs in the general attitude of hospitals. Hence, the adaptation of hospital organizations in SA to provide ICU rehabilitation through multi-disciplinary teamwork including ICU physicians, nurses, social workers, clinical psychologists, and psychiatrists and respiratory, physical, and occupational therapists, in addition to proper referrals to other related clinical disciplines, is pivotal for successfully improving ICU survivorship .Facing the aftermath of post-critical illness disability is a major concern for many ICU survivors. Thus, providing post-ICU care is crucial for facilitating the re-emergence of ICU survivors in their communities. Hospitals should identify the return to health status before ICU admission as a plan of care for ICU survivors. Hospitals should adopt referrals of patients to post-ICU clinics and rehabilitation services, taking into consideration the nature of the delayed recovery time of ICU survivors. The provision of rehabilitation services should address the physical, mental, and social challenges that restrain ICU survivors from returning to work and becoming active members of their community.Globally, there are millions of major surgeries that are performed with a low risk of postoperative complications . HoweverSeveral perioperative approaches, such as optimizing physical activity, pulmonary function, and smoking cessation, are being used to improve recovery and minimize postoperative complications. For example, the effect of preoperative smoking cessation has been well-documented in minimizing postoperative pulmonary complications ,97. Of nCurrently, standardized perioperative rehabilitation protocols are limited. However, in the United Kingdom, the enhanced recovery after surgery (ERAS) approach integrates different perioperative interventions aimed at improving recovery and minimizing postoperative complications . On the In SA, the only perioperative rehabilitations being utilized are early mobilization and breathing exercises. This includes providing patients with an incentive spirometry device postoperatively, which is handled by physiotherapists and respiratory therapists. Therefore, a standardized perioperative rehabilitation protocol aimed at improving patient outcomes and QoL is lacking. Implementing a perioperative rehabilitation protocol such as the I-COUGH approach would improve recovery and QoL in SA. A smoking cessation program may be beneficial for improving pulmonary function before surgery. Patient education, specifically about increasing physical activity before surgery, is essential for improving patient outcomes. All these approaches are worth considering for implementation and should be investigated to improve the QoL in patients undergoing surgery.Audiology and speech–language pathology (SLP) are related to healthcare professions . AudioloSaudi Vision 2030 fosters improved healthcare services, including hearing and speech rehabilitation, through (a) easing access to these services, (b) improving the value of these services, and (c) reinforcing the prevention of health threats . TherefoDiagnosing hearing loss and fitting hearing aids (HAs) are the foremost services conducted by audiologists in SA. To enable those with a hearing loss to use auditory signals effectively and perform better speech communication, the fitting of hearing aids (HAs) is necessary for eligible patients . HoweverSLPs provide services relating to verbal communication skills, including diagnosing and managing communication disorders, improving speech, and managing stuttering. In addition to improving receptive language skills, these areas of practice are the main daily responsibilities of practicing SLPs in SA. According to Alanazi, only 27% of SLPs worked with dysphagic patients in SA . It is eThe dearth of audiology and SLP services in many Saudi regions, except in major cities , was reported in the literature ,129. TheMany audiologists and SLPs reported the need for a better understanding of both fields among other healthcare professionals and in the community, as well as a better recognition of the professions by the national authorities . AlthougSubstance use disorder (SUD) is a global health issue, and SA is no exception . SUD is SUD is highly associated with mental disorders and social stressors . In SA, Globally, studies have revealed that individuals with SUD self-reported poorer QoL than the general population ,146,147.SA’s efforts to tackle SUD are allocated to prevention and treatment services that are both regulated and operationalized under the umbrella of the National Committee for Tobacco Control and the National Committee for Narcotics Control, which were founded by the Council of Ministers and are composed of representatives of several ministries ,158. SUDSUD prevention and treatment are considered comprehensive in SA. However, the integration of QoL elements into rehabilitation is not optimal. There are still areas for improvement in optimizing treatment, preventing relapse, and improving QoL. The first is the adoption of an integrated, multisystem, recovery-oriented model in the treatment of SUD to address its complexity and chronicity . For exaRehabilitation services support individuals with disabilities to be independent and participate actively in their society, which in turn helps them become employed and enhances their QoL . VocatioIn general, more than half of those with disabilities who completed a VR program find employment . EmploymThe Ministry of Human Resources and Social Development in SA is the entity that regulates and the supports VR programs in the country . Such prThe development of comprehensive policies related to health rehabilitation programs should integrate VR as a fundamental component to help individuals with disabilities become independent. As Saudi universities currently do not offer educational certificates in VR, other related degrees, such as occupational therapy, should integrate VR components into their curricula. This would provide occupational therapists with a wider scope for dealing with individuals with disabilities. Moreover, the Ministry of Education should form an initiative to utilize recent research in the field of VR to develop VR-related curricula for inclusion in educational rehabilitation programs in Saudi universities. The Ministry of Human Resources and Social Development should also create policies and initiatives that enhance employment preparation programs to encourage individuals with disabilities to become employed and independent, thereby providing opportunities for them to be active community members. VR in SA is considered suboptimal, and future work should seek improvements in VR services from program components, the allocation of services in healthcare facilities, and the integration of VR into the educational sector. Factors related to increasing awareness and policy development from different government sectors to empower VR program referrals and outcomes are highly warranted. In addition, the long-term follow-up of individuals with disabilities will assess their societal and occupational status in the future.Health rehabilitation services are fundamental components of SA’s vision of promoting a high QoL, especially among individuals with chronic diseases. This review is one of the first to address the current status and future needs of comprehensive health rehabilitation services provided in SA. Experts in different sectors of health rehabilitation across the country have illustrated that the current health rehabilitation services are suboptimal for the individuals involved in health rehabilitation programs. To optimize the QoL of individuals with chronic diseases, the future demands of health rehabilitation services should be tailored based on the unique requirements of each rehabilitation service and the patients it serves .Overall, the shared need to improve all health rehabilitation services in the future include, but are not limited to, the adoption of home-based and telehealth services, the integration of multi-governmental sectors, the empowerment and allocation of health rehabilitation specialists, public awareness campaigns, policy legislation and guideline development, and the implementation of a long-term follow-up system . Urgent Although this study is based on the health rehabilitation services in SA, the experts’ recommendations may be applicable to the wider context of other countries’ health systems as health rehabilitation services are not well optimized globally. The assessments and recommendations presented in this study are limited based on the experts’ opinions, which are subjective to the selection bias of the literature and lack explicit criteria for literature selection and appraisal to mitigate bias. Future researchers shall seek to objectively assess health rehabilitation services in SA from different stakeholders, including policymakers, clinicians, and patients.


Prostate cancer (PCa) is the most common cancer in men. The androgen receptor (AR) has a pivotal role in the pathogenesis and progression of PCa. Many therapies targeting AR signaling have been developed over the years. AR signaling inhibitors (ARSIs), including androgen synthesis inhibitors and AR antagonists, have proven to be effective in castration-sensitive PCa (CSPC) and improve survival, but men with castration-resistant PCa (CRPC) continue to have a poor prognosis. Despite a good initial response, drug resistance develops in almost all patients with metastatic CRPC, and ARSIs are no longer effective. Several mechanisms confer resistance to ARSI and include AR mutations but also hyperactivation of other pathways, such as PI3K/AKT/mTOR. This pathway controls key cellular processes, including proliferation and tumor progression, and it is the most frequently deregulated pathway in human cancers. A significant interaction between AR and the PI3K/AKT/mTOR signaling pathway has been shown in PCa. This review centers on the current scene of different AR and PI3K signaling pathway inhibitors, either as monotherapy or in combination treatments in PCa, and the treatment outcomes involved in both preclinical and clinical trials. A PubMed-based literature search was conducted up to November 2022. The most relevant and recent articles were selected to provide essential information and current evidence on the crosstalk between AR and the PI3K signaling pathways. The ClinicalTrials.gov registry was used to report information about clinical studies and their results using the Advanced research tool, filtering for disease and target. Prostate cancer (PCa) is the most common cancer in men and the second-leading cause of cancer .A more widespread prevention through screening with the prostate-specific antigen (PSA) has shown an increase in PCa incidence rate . Most caThe time of diagnosis influences the prognosis. PCa can be a serious disease, but the majority of diagnosed patients do not die from it unless it becomes more aggressive and castration-resistant. Patients with localized PCa have a survival rate of 90% versus only 67% in metastatic PCa ,5.Treatment for localized PCa includes surgery ), radiotherapy (RT), or active surveillance, depending on the stage of the disease and other factors . DespiteDespite a good initial response, androgen-independent and castration-resistant prostate cancer (CRPC) can occur and the outcome is poor ,15,16. BFurthermore, clinical studies on agents that target the immune checkpoint, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA4), programmed cell death protein 1 (PD1), or programmed death-ligand 1 (PD-L1), have been evaluated in the clinic . To dateHence, in this complex scenario focused on identifying both disease biomarkers and novel and effective treatments that will benefit patients with PCa, this review centers on the current scene of different Phosphatidylinositol-3-kinase (PI3K) signaling pathway inhibitors, either as monotherapy or in combination treatments in PCa, and the treatment outcomes involved in both preclinical and clinical trials.AR signaling has a pivotal role in prostate development and homeostasis as well as in prostate tumorigenesis ,28, due Briefly, androgens, such as testosterone, are synthesized primarily by the Leydig cells in the testes and are tightly regulated by the hypothalamic–pituitary–gonadal (HPG) axis.Once produced, testosterone mostly circulates bound to serum sex hormone-binding globulin (SHBG) and albumin . Only thAR is a member of the steroid and nuclear hormone receptor superfamily and is encoded by the AR gene mapped on the long arm of the X-chromosome (locus: Xq11-q12) ,31. The In the cytoplasm, AR is bound with heat-shock proteins (HSPs)-90, HSP-70, HSP-56, and other chaperone proteins to protect the receptor against degradation ,33.The binding of the ligand promotes the dissociation of AR from these complexes and AR can shuttle to the nucleus, where it dimerizes and binds to the androgen response elements (AREs) ,34. AREsFurthermore, AR transactivation is modulated by coregulators. At least 300 proteins have been identified that can coactivate or co-repress AR-dependent transcription .In addition to the DNA-binding-dependent actions of the AR, commonly referred to as genomic or canonical, the complex androgen-AR can also trigger a signal through a non-DNA-binding-dependent mechanism, referred to as nongenomic. The non-canonical androgen signaling pathways can be classified as non-genomic pathways (triggered by androgens) and outlaw pathways  .Non-genomic androgen signaling pathways include androgen-induced activation of G-protein-coupled receptors (GPCRs), the protein kinase A (PKA) pathway, and via AR variants .Considering that androgens and AR signals are essential regulators in the growth of the normal prostate and play a key role in PCa pathogenesis, they represent a target for many agents, used both as monotherapy or in combination, with the intent to treat and improve the outcome of distinct clinical phenotypes of prostate disease: localized, CSPC, mCSPC, CRPC, and mCRPC. Therapies that aim to inhibit AR signaling, collectively called AR signaling inhibitors (ARSIs), have undergone a significant advance since the 1940s. At that time, Huggins and Hodges demonstrated the therapeutic effect of gonadal testosterone deprivation via orchiectomy ,18,19,20ADT via surgical or chemical castration has become crucial in the treatment of PCa and metastatic disease with the aim to suppress serum testosterone to castration levels and to block the activation of the AR ,15. GonaAndrogen receptor antagonists (ARAs) bind to the LBD of the AR and prevent the binding of testosterone and DHT, so that AR translocation into the nucleus is inhibited and, consequently, the interactions with AREs. The non-steroidal antiandrogens flutamide (Eulexin), nilutamide (Anandron) and bicalutamide (Casodex) represent that the first generation of ARAs do not completely block AR activity  and showDespite these therapies suppressing most PCas, some high-risk prostate cancers gradually progress to CRPC and mCRPC. The AR signaling pathway plays a central role also in the progression of PCa during hormonal therapy ,61,62. SAR gene amplification leads to an overexpression of the AR protein and is the most common genetic mutation among patients with CRPC . ResultsFurthermore, it has been shown that AR gene amplification is frequently detected in the circulating tumor cells (CTCs) of patients with CRPC . As wellPoint mutations in the AR gene are rarely detectable in early-stage PCa but are detected in 15–20% of CRPC patients and up to 40% of CRPC patients treated with AR antagonists, most frequently in the LBD, followed by the NTD ,69. The Androgen receptor splice variants (AR-Vs) are the main causes of abnormalities in AR regulation ,74. AR-VAR-V567es is one of the two most frequently observed AR variants. It has exons 5–7 spliced out and only contains a small portion of the LBD. Results from studies using transgenic mice have shown that ARV567es induces carcinogenesis and accelerates tumor progression . StudiesPIK3R1, PIK3R2, and PIK3R3 genes. Class IB consists of only one catalytic subunit, P110γ, and two regulatory subunits, p84 and p101 [Ras, that directly bind p110. After stimulation, the catalytic subunit of PI3K phosphorylates phosphatidylinositol-4,5-bisphosphate (PIP2) to phosphatidylinositol-3,4,5-triphosphate (PIP3), which acts as a second messenger to recruit a series of proteins containing homology domain with the pleckstrin (PH) of the cell membrane. Uncontrolled signaling of PI3K is very common in cancer, also due to the different roles played by its catalytic subunits p110α and p110β. Mutations in the PI3KA gene encoding p110α have been shown in cancer cells from the colon, lung, prostate, liver, and brain [PTEN)-deficient PCa, ablation of p110β, but not that of p110α, impeded tumorigenesis, with a concomitant diminution in AKT phosphorylation [PTEN-null CRPC, genetic or pharmacological disruption of p110β dramatically slowed the initiation and progression of CRPC [The PI3K/AKT/mammalian target of rapamycin (mTOR) pathway is considered to be a pivotal intracellular signaling pathway and its hyperactivity is correlated with tumor progression in a wide assortment of cancers, counting breast, gastric, ovarian, colorectal, prostate, glioblastoma, and endometrial cancers . PI3K kiand p101 . Class Iand p101 . Finallyand p101 . A variend brain . This gend brain . In an arylation . Consist of CRPC ,95,96.PTEN. The function of PTEN as an oncosuppressor is carried out through its phosphatase activity; it dephosphorylates PIP3 to PIP2, negatively regulating the activation of the PI3K/AKT pathway. This phosphatase can act on both lipids and proteins, and acts by inhibiting cell proliferation and inducing apoptosis. Mutations to PTEN inhibit its oncosuppressive activity. Two major mutations affect the phosphatase domain: one results in the loss of phosphatase activity on both lipids and proteins while the other impairs phosphatase activity on protein substrates. In addition to regulating the PI3K/AKT signaling pathway, PTEN has many other critical roles in tumors, including genomic instability, tumor cell renewal, cell senescence, cell migration, and metastasis. Finally, PTEN plays a significant role in regulating the tumor microenvironment [PTEN gene have been observed in breast, prostate, endometrial, ovarian, colon, melanoma, glioblastoma, and lymphoma cancer [PTEN gene is sufficient to disrupt cell signaling and initiate uncontrolled cell growth [A key molecule in the regulation of PI3K/AKT is ironment . Mutatioa cancer . Studiesl growth . PI3K acl growth . All thrl growth . The besl growth . Finallyl growth . mTOR  and transgenic mouse models have also clearly shown the role of PI3K/AKT/mTOR in the development of PCa. Specifically, overexpression of AKT or biallelic loss of the oncosuppressor  in vivo . PTEN de of mTOR . Others are lost . This deic forms . Moreoveic forms . From a ic forms . Howeveric forms . These dic forms .On the other hand, inactivation of AR would lead to over-regulation of the PI3K/AKT pathway, which has been correlated with altered control of cell growth and survival, increased metastatic competence, angiogenesis, and resistance to chemotherapy.Indeed, it has been demonstrated that AR inhibition activates AKT signaling by reducing the expression of the AKT phosphatase PHLPP . AR blocThus, these two pathways are regulated by a reciprocal feedback mechanism in that the inhibition of one inactivates the other, allowing for cancer cell survival and progression.p = 0.09) [p = 0.0335) [Because inhibiting either AR or AKT often activates the other, a combination therapy might be advantageous. Over 40 compounds targeting key components in the PI3K-induced signaling pathway have been investigated to date. AZD5363, an inhibitor of all isoforms of Akt, has been reported to inhibit proliferation and induce apoptosis in prostate cancer cell lines expressing AR and has antitumor activity in vivo in androgen-sensitive LNCaP xenograft models resistant to castration . However = 0.09) . Another 0.0335) . The pha 0.0335) . Moreove 0.0335) . It mustThe high incidence of prostate cancer in the global male population has resulted in many efforts being channeled into finding the best therapeutic strategies. In particular, the prognosis of mCRPC remains very poor to date since patients develop resistance to treatments. Indeed, there is currently no single therapeutic choice for these patients, but recommended therapies involve the use of agents targeting different signaling pathways, often in combination or as neoadjuvant therapies. Many studies have confirmed the role of the PI3K/AKT/mTOR signaling pathway in the development of treatment resistance and tumor progression. Indeed, activation of PI3K increases proliferation and prevents apoptosis of prostate cancer cells, while inactivation promotes cell cycle arrest in the G phase. On the other hand, there is evidence that AR inhibition promotes upregulation of the PI3K pathway, and vice versa, via a negative feedback mechanism.Therefore, studies aiming to understand the key mechanisms that induce resistance within this continuous crosstalk between the two signaling pathways are needed to improve the outcome of patients with prostate cancer.


Prior to and after 12 weeks of a hybrid exercise-based cardiac rehabilitation program, grip strength (handgrip), leg strength (chair stand test), and functional exercise capacity  were assessed. The hybrid exercise-based cardiac rehabilitation program resulted in a 9.4 ± 14.6% and a 6.2 ± 12.1% grip strength increase, a 14.4 ± 39.4% and a 28.9 ± 48.1% legs strength increase, and a 14.6 ± 26.4% and a 6.8 ± 14.0% functional exercise capacity improvement in ADULT and OLDER, respectively (p < 0.05) with no differences between groups. In conclusion, a hybrid exercise-based cardiac rehabilitation program could increase muscle strength and improve functional exercise capacity in adults and older people with coronary artery disease. More future studies comparing effectiveness among these age groups are needed to strengthen this conclusion.Coronary heart disease is the most common cause of death worldwide. Standard cardiac rehabilitation (face-to-face sessions) has shown benefits in increasing muscle strength and functional exercise capacity in adults and older people. However, it is unknown whether hybrid cardiac rehabilitation (a first face-to-face phase + a second remote monitoring phase) will have similar benefits in adults versus older subjects. The aim of this study was to compare the effects of a hybrid exercise-based cardiac rehabilitation program on muscle strength and functional exercise capacity in “adult” versus “older” people with coronary artery disease. We hypothesized that a hybrid exercise-based cardiac rehabilitation program would improve muscle strength and functional exercise capacity, but the impact would be smaller in the older group than the adult individuals. This study is part of a larger project . We subjected 22 adult (<60 y) females and males (ADULT;  Coronary heart disease is the most common cause of death worldwide . In thisAmong the treatment strategies, cardiac rehabilitation based on physical exercise has been shown to improve muscle strength , increasAlternatives to standard rehabilitation (face-to-face center-based sessions) have been proposed, such as telerehabilitation, messaging through the use of mobile devices, among others . A recenCombining a first phase of rehabilitation where face-to-face sessions and a second phase with remote accompaniment are carried out can be called “hybrid rehabilitation”. This hybrid cardiac rehabilitation yields similar benefits to the training program in the center for patients with coronary disease , reducinOn the other hand, it is international knowledge that our population is aging and a large percentage of older people have or will have coronary heart disease . TherefoTherefore, in the present study we aimed to compare the effects of a hybrid exercise-based cardiac rehabilitation program on muscle strength and functional exercise capacity in “adult” versus “older” people with coronary artery disease. Secondarily, we also looked at blood pressure and body composition results. We hypothesized that a hybrid exercise-based cardiac rehabilitation program would improve muscle strength and functional exercise capacity, but the impact would be smaller in the older group than the adult individuals.n = 5/17 (f/m); 52 ± 5 y; 28.9 ± 3.4 kg·m-2) and 20 elderly (≥60 y) females and males ; 66 ± 4 y; 27.4 ± 3.9 kg·m-2) with coronary artery disease were included. This study is part of a larger project  that already has prior publications  females and males  or stable coronary disease diagnosed by angiography or a stress test; patient treated medically  or by thrombolysis, angioplasty or revascularization surgery; patient with physician referral, who can start cardiac rehabilitation between 2 weeks and 2 months from their event, diagnosis or procedure; patient able to attend the health center almost twice a week over 4–6 weeks; and patient with a mobile phone. Exclusion criteria were: patient has a planned repeat cardiac or other procedure in next 12 months; explicit contraindication to perform exercise based on American College of Sport Medicine guidelines ; patientTen supervised sessions by a physiotherapist were carried out in a period of 4–6 weeks. Each session included aerobic and resistance training. The training intensity was moderate, starting the rehabilitation program with a duration of 10 min per session up to 60 min per session according to tolerance. In addition to the above, throughout the exercise sessions, self-efficacy-based counseling was provided by the physiotherapist on physical activity, diet, tobacco and medication use.After 6 weeks of face-to-face rehabilitation, participants were encouraged to maintain the same exercise prescription, eat healthy and have good adherence to their prescribed medications through phone calls twice a week and text messages three times a week for 6 weeks .Upper and lower body strength were assessed through grip strength and the chair stand test, respectively. Grip strength was performed with a Jamar® Plus+ electronic handheld dynamometer  with the participant seated. Three attempts were made on each hand alternately with 30 s of rest. The highest value of the 6 attempts was reported . The chaThe 6-minute walking test (6MWT) was conducted following the recommendations of the ATS Statement . In shorBody weight, height, blood pressure, and waist circumference were assessed by a trained evaluator. Body mass index (BMI) was determined by weight in kilograms divided by height in meters squared. Body weight measurement was performed with the least possible clothing. Height was assessed with the participant barefoot, looking straight ahead at a fixed point, and in inspiration. Both measurements were made on a balance with a stadiometer . Measurement of blood pressure was performed through an automatic blood pressure monitor  on the participant’s right arm, after remaining seated for 5 min . Waist cData are presented as mean ± standard deviation. To analyze the normality of the data, the Shapiro-Wilk test was used. At baseline, data between groups were compared with an independent samples t-test for quantitative variables and a Chi-square test for qualitative variables. Pre- versus post-intervention data were analyzed using a repeated-measures ANOVA with time (PRE versus POST) as the within-subjects factor and group (ADULT versus OLDER) as the between-subjects factor. In the case of a significant interaction, paired t-tests were performed to determine time effects within groups and independent t-tests for group differences in the PRE, and POST-evaluations values, using an α level of 0.05. Additionally, a partial eta squared (η2) was used to estimate effect sizes for ANOVA and Cohen’s d (d) for t-test. All calculations were performed using SPSS version 24.0 .p < 0.001).In the HYCARET study (standard vs. hybrid cardiac rehabilitation), 191 underwent a cardiac rehabilitation program. A subsample of 42 participants, 22 participants in the ADULT group (<60 years) and 20 participants in the OLDER group (≥60 years) in the hybrid cardiac rehabilitation group had completed all the evaluations included in the present report. The flow diagram of the study participants is shown in p = 0.001; η2 = 0.26). Similarly, 12 weeks of cardiac rehabilitation program resulted in an increase in legs strength . No differences in the response to the cardiac rehabilitation program were observed between groups in all strength variables .After the hybrid exercise-based cardiac rehabilitation program, grip strength  increasestrength  from 14.p > 0.05) and the effect sizes were d = 0.24 and d = 0.33, respectively.Accordingly, the delta increase in grip and legs strength did not differ between ADULT and OLDER  with no differences between groups . Accordingly, the relative increase in functional exercise capacity did not differ between ADULT (14.6 ± 26.4%) and OLDER .Hybrid exercise-based cardiac rehabilitation program increased functional exercise capacity after 12 weeks , from 49p > 0.05; all η2≤0.09; After the hybrid exercise-based cardiac rehabilitation program, no significant differences were observed in weight, BMI, blood pressure , or waist circumference between ADULT vs. OLDER  hybrid exercise-based cardiac rehabilitation program would improve muscle strength and functional exercise capacity in both groups, and 2) the impact after cardiac rehabilitation program on muscle strength and functional exercise capacity would be smaller in the older group when compared to the adult individuals.Due to limited time and resources and the health pandemic we are experiencing (COVID-19), new ways of delivering therapeutic strategies in patients with coronary artery disease have emerged. One of the proposed strategies is hybrid cardiac rehabilitation. This study evidences that adult and older patients with coronary artery disease benefit in their gains in muscle strength and functional exercise capacity after 12 weeks of a hybrid exercise-based cardiac rehabilitation program.The normal aging process leads to a decrease in muscle mass, strength and physical performance . In oldeStrategies like exercise-based cardiac hybrid rehabilitation have turned out to be an effective strategy to improve strength and functional exercise capacity in older people. The Cochrane Review update on this topic supports that cardiac rehabilitation benefits people with coronary heart disease, reducing the risk of myocardial infarction, somewhat reducing all-cause mortality, and greatly reducing all-cause hospitalization, thereby reducing health costs and improving quality of life at 12 months .Despite all the benefits reported by cardiac rehabilitation, it is underutilized in older people. For this reason, new delivery strategies like hybrid cardiac rehabilitation could help increase adherence and reach of this type of therapy to the elderly population . In addiIn addition, the study by In this study, we compared performing standard cardiac rehabilitation (12 weeks of face-to-face sessions) versus hybrid cardiac rehabilitation (6 weeks of face-to-face sessions + 6 weeks of remote monitoring). This decision is due to the fact that access to cardiac rehabilitation is limited in Chile  due to limited human and physical resources. With such innovative proposals, we intend to be able to improve access for patients with coronary artery disease, especially older people, in the future. Also, it has been observed in cardiac surgery patients that hybrid cardiac rehabilitation is as effective as a hospital-based program in reducing pain components and it includes only 38% of the total cost in comparison to hospital-based delivery, so could be economically suitable to be also recommended to the coronary artery disease patients . In the Due to the associated comorbidities, medical referral to cardiac rehabilitation is less indicated in people over 60 years . Age shoOur study has limitations; the loss to follow-up due to the COVID-19 pandemic resulted in a high number of participants with missing measurements, which compromised the statistical power of knowing if there are differences between groups. For this reason, the findings should be taken with caution pending further studies.In conclusion, a hybrid exercise-based cardiac rehabilitation program could increase muscle strength and improve functional exercise capacity in adults and older people with coronary artery disease. More future studies comparing effectiveness among these age groups are needed to strengthen this conclusion.


E (IgE)-mediated. Noncoding RNA (ncRNA) is an important regulator involved in gene expression and can be detected in the cytoplasm or extracellular fluid, which mainly includes microRNAs , long noncoding RNAs , and circRNAs. LncRNA and miRNA both participate in the regulation of immune function. Some respiratory viral infections can aggravate allergic rhinitis, such as a respiratory syncytial virus (RSV) and human metapneumovirus (hMPV). However, the interaction between viral infection and allergy is complex and the mechanism is still unclear. In this review, we summarized the interactions of noncoding RNAs and viruses in the occurrence and development of AR, along with the treatments focusing on the noncoding RNAs in the past five years.Allergic rhinitis (AR) is a type I hypersensitivity reaction disease caused by inhaled allergens and immunoglobulin  E (IgE)-mediated. At present, the morbidity of AR is estimated between 10% and 40% worldwide, with even up to 50% in some countries [+T cells [+T cells are activated and differentiated into allergen-specific helper T cells type 2 (Th2 cells), which activate B cells to differentiate into plasma cells, resulting in the production of allergen-specific IgE [Allergic rhinitis (AR) is a type I hypersensitivity reaction disease caused by inhaled allergens and immunoglobulin ountries . When alific IgE –8 and reific IgE .+ and CD8+T cells, with phased expression [Noncoding RNA (ncRNA) is an important regulator involved in gene expression and can be detected in the cytoplasm or extracellular fluid, which mainly includes microRNAs , long noncoding RNAs , and circRNAs , 11. Allpression , 16. At pression . These rViral tinfections are known to aggravate AR. Although, the interaction between viral infection and allergy is complex and the mechanisms remain unclear. Some studies suggest that coregulatory molecules and cytokines may play a role . Viral rIn this review, we will focus on how noncoding RNA and viruses interact to jointly regulate the occurrence and development of allergic rhinitis, as well as the latest research progress on virus-like particles and targeted noncoding RNA therapy in the treatment of allergic rhinitis patients.α, interleukin, and chemotherapeutic factors), as well as activation of white blood cells at the infection site, resulting in impaired lung function, persistent bronchial hyperreactivity, and airway inflammation, promoting Th2 cell sensitization and inducing allergic rhinitis [+ T cells and affect cytokine signal transduction through STAT5. SOCS1 is a direct target of miR-155, and the inhibition of miR-155 can restore SOCS1 expression. Overexpression of miR-155 can reduce SOCS1 expression level [Infectious eukaryotic viruses play an important role in acute upper respiratory tract infections. RSV and hMPV are the main viruses that cause allergic rhinitis and are also risk factors for AR . These vrhinitis . Microarrhinitis . Membersrhinitis , 27. In rhinitis . MiR-155rhinitis . After Rrhinitis . MiR-155on level . TherefoεRI signaling pathway and NF‐κB signaling pathway [α and IL-6 are highly expressed in AR subjects and are important proinflammatory factors regulating the inflammatory response of AR. Studies have shown that their single nucleotide polymorphisms (SNPs) may be risk factors for AR susceptibility [α and IL-6 by the activity of the NF-κB signaling pathway in OVA mice [α-asarone and found that the viability, proliferation, and migration of RSV-ASMCs were significantly reduced, which is mediated by the PVT1/ miR-203a/E2F3 signaling pathway [Studies have found that lncRNA is associated with AR. One study showed that analysis of lncRNA cores showed that there were 2259 lncRNA in the nasal mucous membrane of AR patients, of which 1033 were up-regulated and 1226 down-regulated . Genetic pathway . Recentl pathway . TNF-α atibility . In additibility . The resOVA mice . We have pathway . These rAccording to the definition proposed by the ARIA  initiative allergic rhinitis is an IgE-mediated inflammatory response of the nasal epithelium with corresponding symptoms caused by exposure to allergens . Althoug+CD4+CD25+ natural regulatory T cells (nTreg) both play an important role in controlling pathogenic effector T cells and maintaining the balance between immune tolerance and immunity, which can down-regulate dendritic cells, mast cells, eosinophil and basophils, and helper T cells [β are inhibitory cytokines that play an important role in this regard. When we restored the balance between Th2/Th1/Treg with VLPs, the ratio between allergen-specific IgE and IgG4 antibodies was reduced, resulting in higher IgG4 production and reduced migration of inflammatory cells to tissues, resulting in reduced clinical symptoms in AR patients.So how does AIT work? A dendritic cell, one of the antigen-presenting cells, is believed to play a central role in the absorption and processing of allergens to induce allergen-specific immune responses. In the presence of high doses of allergens, the physical immune system will tolerate the phenomenon, which leads to an imbalance between Th1 and Th2. Regulatory T cells (iTreg) and thymus-derived FOXP3 T cells . What's In addition, several ncRNA-virus products are being actively developed. RNA interference (RNAi) is a gene-specific RNA degradation process mediated by short interfering RNA (siRNA), which is a novel therapeutic vector for allergic rhinitis . CalciumIn conclusion, miRNA can target AR-related gene expression, while lncRNA can combine with miRNA through competition, and total also involved in AR epigenetic modification. On the other hand, lncRNA also may be involved in the pathogenesis of AR through multiple functional pathways. In addition, extracellular exosomes lncRNA is gaining increasing attention in AR. Further exploration of RNA in many ways will greatly expand the genes and molecules involved in the research on the mechanism of action in AR and other allergic diseases will provide the accuracy of AR in future therapy and offer new directions. Viral infections, like respiratory syncytial virus (RSV) and human metapneumovirus (hMPV), could interact with the noncoding RNA. However, the interaction between viral infection, noncoding RNA, and allergy is complex. At present, the research on allergic rhinitis is more and more in-depth, and the regulatory network of lncRNA is gradually improved, which is conducive to the development of new treatment methods and the discovery of new molecular markers for rapid diagnosis and classification.