Expectancy about the future and its effect on action.
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۞قُلۡ يَٰعِبَادِيَ ٱلَّذِينَ أَسۡرَفُواْ عَلَىٰٓ أَنفُسِهِمۡ لَا تَقۡنَطُواْ مِن رَّحۡمَةِ ٱللَّهِۚ إِنَّ ٱللَّهَ يَغۡفِرُ ٱلذُّنُوبَ جَمِيعًاۚ إِنَّهُۥ هُوَ ٱلۡغَفُورُ ٱلرَّحِيمُ
Say, ‘[God says], My servants who have harmed yourselves by your own excess, do not despair of God’s mercy. God forgives all sins: He is truly the Most Forgiving, the Most Merciful
قَالَ وَمَن يَقۡنَطُ مِن رَّحۡمَةِ رَبِّهِۦٓ إِلَّا ٱلضَّآلُّونَ
He said, ‘Who but the misguided despair of the mercy of their Lord?’
وَإِذَآ أَذَقۡنَا ٱلنَّاسَ رَحۡمَةࣰ فَرِحُواْ بِهَاۖ وَإِن تُصِبۡهُمۡ سَيِّئَةُۢ بِمَا قَدَّمَتۡ أَيۡدِيهِمۡ إِذَا هُمۡ يَقۡنَطُونَ
When We give people a taste of Our blessing, they rejoice, but when something bad happens to them- because of their own actions- they fall into utter despair
فَبِمَا رَحۡمَةࣲ مِّنَ ٱللَّهِ لِنتَ لَهُمۡۖ وَلَوۡ كُنتَ فَظًّا غَلِيظَ ٱلۡقَلۡبِ لَٱنفَضُّواْ مِنۡ حَوۡلِكَۖ فَٱعۡفُ عَنۡهُمۡ وَٱسۡتَغۡفِرۡ لَهُمۡ وَشَاوِرۡهُمۡ فِي ٱلۡأَمۡرِۖ فَإِذَا عَزَمۡتَ فَتَوَكَّلۡ عَلَى ٱللَّهِۚ إِنَّ ٱللَّهَ يُحِبُّ ٱلۡمُتَوَكِّلِينَ
By an act of mercy from God, you [Prophet] were gentle in your dealings with them- had you been harsh, or hard-hearted, they would have dispersed and left you- so pardon them and ask forgiveness for them. Consult with them about matters, then, when you have decided on a course of action, put your trust in God: God loves those who put their trust in Him
وَلَئِن سَأَلۡتَهُم مَّنۡ خَلَقَ ٱلسَّمَٰوَٰتِ وَٱلۡأَرۡضَ لَيَقُولُنَّ ٱللَّهُۚ قُلۡ أَفَرَءَيۡتُم مَّا تَدۡعُونَ مِن دُونِ ٱللَّهِ إِنۡ أَرَادَنِيَ ٱللَّهُ بِضُرٍّ هَلۡ هُنَّ كَٰشِفَٰتُ ضُرِّهِۦٓ أَوۡ أَرَادَنِي بِرَحۡمَةٍ هَلۡ هُنَّ مُمۡسِكَٰتُ رَحۡمَتِهِۦۚ قُلۡ حَسۡبِيَ ٱللَّهُۖ عَلَيۡهِ يَتَوَكَّلُ ٱلۡمُتَوَكِّلُونَ
If you [Prophet] ask them, ‘Who created the heavens and earth?’ they are sure to answer, ‘God,’ so say, ‘Consider those you invoke beside Him: if God wished to harm me, could they undo that harm? If God wished to show me mercy, could they withhold that mercy?’ Say, ‘God is enough for me: all those who trust should put their trust in Him.’
وَلَا تَهِنُواْ وَلَا تَحۡزَنُواْ وَأَنتُمُ ٱلۡأَعۡلَوۡنَ إِن كُنتُم مُّؤۡمِنِينَ
Do not lose heart or despair- if you are true believers you have the upper hand
Commentary on the verses above, at most two editions per verse.
Say: “O My servants who have been immoderate against yourselves, despair not of God's mercy. Surely God forgives the sins altogether.” Know that among God's creatures, perfect honor belongs to two groups: angels and Adamites. This is why He appointed prophets and messengers from among these two groups rather than any others. Their utmost eminence lies in two things: servanthood and love. Sheer servanthood is the attribute of the angels, and servanthood and love are both attributes of the Adamites. He gave the angels sheer servanthood, which is the attribute of creation. Along with servant- hood He gave the Adamites the robe of love, which is the attribute of the Real. Thus He says con- cerning this community, “He loves them, and they love Him” [5:54]. He also gave the Adamites superiority over the angels in servanthood, for He said that servanthood is the angels' attribute, but without a
Say that God declares ‘O My servants who have been prodigal against their own souls do not despair read taqnitū taqnatū or taqnutū do not give up hope of God’s mercy. Truly God forgives all sins for those who repent from idolatry. Truly He is the Forgiving the Merciful.
It was by a mercy of God that thou wert soft with them. Hadst thou been harsh and hard of heart, they would have scattered from around thee. So pardon them, ask forgiveness for them, and consult with them in the affair. And when thou art resolved, trust in God. Surely God loves those who trust. “O master of masters! O paragon of engendered beings! You are generous and lovingly kind, gentle and ever-merciful to everyone. You drive everyone by customs that hit the mark. You call everyone to the table of exaltedness and convey to everlasting felicity. You are like a father for the orphans, a husband for the widowed. You caress the familiar and you show the road to the estranged. You are mercy itself for the world's folk, a cause of generous giving to all the servants. O master, there is all of this, but take care not to see yourself. Do not consider these as your own acquisitions, for all o
He said ‘And who — in other words no one — despairs read yaqnitu or yaqnatu of the mercy of his Lord save those who are astray?’ save disbelievers.
And when We let people that is people such as the disbelievers of Mecca and others taste some mercy some grace they exult in it an exultation of arrogance. But if some evil some hardship befalls them for what their own hands have sent ahead behold! they despair of mercy. It is in the nature of a believer to give thanks in times of grace and to hope for mercy from his Lord in times of hardship.
And tell them about the guests (i. e., the angels) of Ibrahim (51)When they entered upon him, and said: "Salaman (peace!)." He said: "Indeed we are frightened of you. (52)They said: "Do not be afraid! We bring you the good news of a boy possessing much knowledge and wisdom. (53)He said: "Do you give me this good news while old age has overtaken me? Of what then is your news about? (54)They said: "We give you good news in truth. So do not be of those who despair. (55)He said: "And who despairs of the mercy of his Lord except those who are astray? (56) The Guests of Ibrahim and their Good News of a Son for Him Allah is saying: 'Tell them, O Muhammad, about the story of ضَيْفِ إِبْرَاهِيمَ (the guests of Ibrahim.)' دَخَلُوا عَلَيْهِ فَقَالُوا سَلَامًا قَالَ إِنَّا مِنكُمْ وَجِلُونَ (they entered upon him, and said: "Salaman (peace!)." He said: "Indeed we are frightened of you.") meani
Sound narrations only, and never matched by text. A narration appears here because a compiler filed it under a chapter this subject maps to, or because someone read it and anchored it. Each row says which.
حَدَّثَنَا قُتَيْبَةُ بْنُ سَعِيدٍ، حَدَّثَنَا اللَّيْثُ، عَنْ سَعِيدِ بْنِ أَبِي سَعِيدٍ الْمَقْبُرِيِّ، عَنْ أَبِيهِ، عَنْ أَبِي هُرَيْرَةَ، عَنْ رَسُولِ اللَّهِ صلى الله عليه وسلم أَنَّهُ قَالَ " إِنَّ فِي الْجَنَّةِ لَشَجَرَةً يَسِيرُ الرَّاكِبُ فِي ظِلِّهَا مِائَةَ عَامٍ" . وَفِي الْبَابِ عَنْ أَنَسٍ وَأَبِي سَعِيدٍ . قَالَ أَبُو عِيسَى هَذَا حَدِيثٌ صَحِيحٌ .
Abu Hurairah narrated that the Messenger of Allah (s.a.w) said:"Verily, in Paradise there is a tree, a rider will travel in it's shade for a hundred years." Other chains report similar narrations
حَدَّثَنَا عَبَّاسٌ الدُّورِيُّ، حَدَّثَنَا عُبَيْدُ اللَّهِ بْنُ مُوسَى، عَنْ شَيْبَانَ، عَنْ فِرَاسٍ، عَنْ عَطِيَّةَ، عَنْ أَبِي سَعِيدٍ الْخُدْرِيِّ، عَنِ النَّبِيِّ صلى الله عليه وسلم قَالَ " فِي الْجَنَّةِ شَجَرَةٌ يَسِيرُ الرَّاكِبُ فِي ظِلِّهَا مِائَةَ عَامٍ لاَ يَقْطَعُهَا وَقَالَ ذَلِكَ الظِّلُّ الْمَمْدُودُ " . قَالَ أَبُو عِيسَى هَذَا حَدِيثٌ حَسَنٌ غَرِيبٌ مِنْ حَدِيثِ أَبِي سَعِيدٍ .
Abu Sa'eed Al-Khudri narrated that the Prophet (s.a.w) said:"In Paradise there is a tree, a rider will travel in its shade for a hundred years without reaching an end." He said: "And that is the extended shade
حَدَّثَنَا عَبَّاسُ بْنُ عَبْدِ الْعَظِيمِ الْعَنْبَرِيُّ، وَغَيْرُ، وَاحِدٍ، قَالُوا حَدَّثَنَا أَبُو دَاوُدَ الطَّيَالِسِيُّ، حَدَّثَنَا عِمْرَانُ الْقَطَّانُ، عَنْ قَتَادَةَ، عَنْ سَعِيدِ بْنِ أَبِي الْحَسَنِ، عَنْ أَبِي هُرَيْرَةَ، رضى الله عنه عَنِ النَّبِيِّ صلى الله عليه وسلم قَالَ " لَيْسَ شَيْءٌ أَكْرَمَ عَلَى اللَّهِ تَعَالَى مِنَ الدُّعَاءِ " . قَالَ أَبُو عِيسَى هَذَا حَدِيثٌ حَسَنٌ غَرِيبٌ لاَ نَعْرِفُهُ مَرْفُوعًا إِلاَّ مِنْ حَدِيثِ عِمْرَانَ الْقَطَّانِ وَعِمْرَانُ الْقَطَّانُ هُوَ ابْنُ دَاوَرَ وَيُكْنَى أَبَا الْعَوَّامِ . حَدَّثَنَا مُحَمَّدُ بْنُ بَشَّارٍ، حَدَّثَنَا عَبْدُ الرَّحْمَنِ بْنُ مَهْدِيٍّ، عَنْ عِمْرَانَ الْقَطَّانِ، بِهَذَا الإِسْنَادِ نَحْوَهُ .
Abu Hurairah narrated that:The Prophet said: “There is nothing more honorable with Allah [Most High] than supplication.”
حَدَّثَنَا أَحْمَدُ بْنُ مَنِيعٍ، حَدَّثَنَا مَرْوَانُ بْنُ مُعَاوِيَةَ، عَنِ الأَعْمَشِ، عَنْ ذَرٍّ، عَنْ يُسَيْعٍ، عَنِ النُّعْمَانِ بْنِ بَشِيرٍ، عَنِ النَّبِيِّ صلى الله عليه وسلم قَالَ " الدُّعَاءُ هُوَ الْعِبَادَةُ " . ثُمَّ قَرَأََ : (وقالَ رَبُّكُمُ ادْعُونِي أَسْتَجِبْ لَكُمْ إِنَّ الَّذِينَ يَسْتَكْبِرُونَ عَنْ عِبَادَتِي سَيَدْخُلُونَ جَهَنَّمَ دَاخِرِينَ ) . قَالَ هَذَا حَدِيثٌ حَسَنٌ صَحِيحٌ . وَقَدْ رَوَاهُ مَنْصُورٌ وَالأَعْمَشُ عَنْ ذَرٍّ وَلاَ نَعْرِفُهُ إِلاَّ مِنْ حَدِيثِ ذَرٍّ . هُوَ ذَرُّ بْنُ عَبْدِ اللَّهِ الْهَمْدَانِيُّ ثِقَةٌ وَالِدُ عُمَرَ بْنِ ذَرٍّ .
An-Nu`man bin Bashir narrated that:The Prophet said: “The supplication, is worship.” Then he recited: And Your Lord said: “Call upon me, I will respond to you. Verily, those who scorn My worship, they will surely enter Hell humiliated
Arabic originals, reached through the subject’s Arabic senses. Interpretive sources, never proof of a ruling.
والثالث : رجل متماد في التفريط والخطايا يرجو رحمة الله بلا عمل فهذا هو الغرور والتمني والرجاء الكاذب
ولهذا قيل في حد الرجاء هو النظر إلى سعة رحمة الله
وإن نظرنا إلى موضع الخوف والرجاء فالرجاء أفضل لأن الرجاء يستقي من بحر الرحمة، والخوف يستقي من بحر الغضب.
وقال أبو الفرج بن الجوزي رحمه الله تعالى سمع المهلب فتى يتغنى بشعر في جارية له فقال المهلب
وسئل الإمام أبو الفرج بن الجوزي رحمه الله بأبيات
والقصد : أن ملاحظة حسن العاقبة تعين على الصبر فيما تتحمله باختيارك وغير اختيارك والثاني : انتظار روح الفرج يعني راحته ونسيمه ولذته فإن انتظاره ومطالعته وترقبه يخفف حمل المشقة ولا سيما عند قوة الرجاء أو القطع بالفرج فإنه يجد في حشو البلاء من روح الفرج ونسيمه وراحته : ما هو من خفي الألطاف وما هو فرج معجل وبه وبغيره يفهم معنى اسمه اللطيف
Peer-reviewed work held with its DOI and abstract, labelled with the study design its publication types report. None of it has been read or assessed, so nothing here may be cited as showing anything. Retracted work is held for the record but never listed; a review that a later version replaced is listed under its replacement and marked.
Hope, optimism, self-efficacy, and posttraumatic stress disorder: A meta-analytic review of the protective effects of positive expectancies.: Objective: The present meta-analysis consolidated research examining how positive expectancies (e.g., hope, self-efficacy, and optimism) may protect against the development of posttraumatic stress disorder (PTSD). Method: Articles were identified by searching PILOTS, PsycINFO, PubMed, and ProQuest Dissertations and Theses databases. Results: Aggregated results from 154 studies indicated that positive expectancies were associated with lower levels of PTSD symptoms. This relationship was stronger
Hope, optimism and survival in a randomised trial of chemotherapy for metastatic colorectal cancer.: Purpose: Psychological responses to cancer are widely believed to affect survival. We investigated associations between hope, optimism, anxiety, depression, health utility and survival in patients starting first-line chemotherapy for metastatic colorectal cancer. Methods: Four hundred twenty-nine subjects with metastatic colorectal cancer in a randomised controlled trial of chemotherapy completed baseline questionnaires assessing the following: hopefulness, optimism, anxiety and depression and h
Personal recovery in bipolar disorder: Systematic review and "best fit" framework synthesis of qualitative evidence - a POETIC adaptation of CHIME.: Background: Personal recovery, living a satisfying, hopeful life alongside symptoms, has become an increasingly valued aim across mental health care agendas internationally. However, there is little understanding of how people experience personal recovery alongside the mood challenges characteristic of a bipolar disorder diagnosis. Personal recovery frameworks have been developed for populations with mixed psychiatric diagnoses, predominantly psychotic disorders. Methods: This systematic review
Levels of psychological capital among nurses: A systematic review and meta-analysis.: Aim: To systematically evaluate the available literature about overall levels of psychological capital among nurses. Background: Psychological capital is described as a positive mental state associated with nurses' mental health, quality of care and patient outcomes. Methods: A search was carried out using PubMed, Web of Science, EMBASE, CINAHL, PsycINFO, Cochrane Library and Chinese Database, including China National Knowledge Infrastructure (CNKI), Chinese Biological Medical (CBM), WanFang and
Meta-Analyses of Predictors of Hope in Adolescents.: The purposes of this study were to identify predictors of hope in the literature reviewed, to use meta-analysis to determine the mean effect size (ES) across studies between each predictor and hope, and to examine four moderators on each predictor-hope relationship. Using preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines for the literature reviewed, 77 published studies or doctoral dissertations completed between 1990 and 2012 met the inclusion criteria. Elev
Understanding the experiences of hikikomori through the lens of the CHIME framework: connectedness, hope and optimism, identity, meaning in life, and empowerment; systematic review.: Background: Hikikomori is a phenomenon describing people who exhibit behaviors of self-secluding themselves at home for long durations of time and usually only having face-to-face social interactions with none other than family. Existing interventions for hikikomori are inconclusive and the majority are absent in using a theoretical framework to guide its components. Therefore, applicability of the psychosocial recovery framework of Connectedness, Hope and Optimism, Identity, Meaning in Life, an
Pregnancy in Cystic Fibrosis-Past, Present, and Future.
The introduction of mutation-specific therapy led to a revolution in cystic fibrosis (CF) care. These advances in CF therapies have changed the disease profile from a severe incurable disease with limited survival to a treatable disease with improved quality of life and survival into adulthood. CF patients are now able to plan their future, including marriage and parenthood. Side by side with the optimism, new issues and concerns are arising, including fertility and preparation for pregnancy, maternal and fetal care during pregnancy, and post-partum care. While cystic fibrosis transmembrane regulator (CFTR) modulators show promising results for improving CF lung disease, data on their safety in pregnancy are still limited. We performed a literature review on pregnancy in CF from the past, with the first described pregnancy in 1960, through the current fascinating changes in the era of CF…
matched on optimism (text), hope (text)
An exploration of loneliness experienced by people living with mental illness and the impact on their recovery journey: An integrative review.
WHAT IS KNOWN ON THE SUBJECT?: There is evidence that social isolation and loneliness is more prevalent in people living with mental illness than in the general population. People living with mental illness frequently experience stigma, discrimination, rejection, repeated psychiatric admissions, low self-esteem, low self-efficacy, and increased symptoms of paranoia, depression, and anxiety. There is evidence of common interventions that can be used to improve loneliness and social isolation such as psychosocial skills training and cognitive group therapy. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: This paper offers a comprehensive assessment of the evidence between mental illness, loneliness, and recovery. The results suggest that people living with mental illness experience elevated levels of social isolation and loneliness leading to poor recovery and quality of life. Social deprivati…
matched on optimism (text), hope (text)
l-glutamine, crizanlizumab, voxelotor, and cell-based therapy for adult sickle cell disease: Hype or hope?
For more than two decades, hydroxyurea was the only therapeutic agent approved by the Food and Drug Administration (FDA) for sickle cell disease (SCD). Although curative allogeneic hematopoietic stem cell transplants (allo-HSCT) were also available, only very few patients underwent the procedure due to lack of matched-related donors. However, therapeutic options for SCD patients increased dramatically in the last few years. Three new agents, l-glutamine, crizanlizumab, and voxelotor, were approved by the FDA for use in SCD patients. The number of SCD patients who underwent allo-HSCT also increased as a result of advances in the prevention of graft failure and graft-versus-host disease from using mismatched donor HSC. More recently gene therapy was made available on clinical trials. The increased treatment options for SCD have led to a sense of optimism and excitement among many physician…
matched on optimism (text), hope (text)
The involvement of rare disease patient organisations in therapeutic innovation across rare paediatric neurological conditions: a narrative review.
Background: The patient voice is becoming increasingly prominent across all stages of therapeutic innovation. It pervades research domains from funding and recruitment, to translation, care, and support. Advances in genomic technologies have facilitated novel breakthrough therapies, whose global developments, regulatory approvals, and confined governmental subsidisations have stimulated renewed hope amongst rare disease patient organisations (RDPOs). With intensifying optimism characterising the therapeutic landscape, researcher-advocate partnerships have reached an inflexion point, at which stakeholders may evaluate their achievements and formulate frameworks for future refinement. Main text: Through this narrative review, we surveyed relevant literature around the roles of RDPOs catering to the rare paediatric neurological disease community. Via available literature, we considered RDPO…
matched on optimism (text), hope (text)
Promise, perils and cautious optimism: the next frontier in long-acting modalities for the treatment and prevention of HIV.
Purpose of review: This paper provides a critical review of recent therapeutic advances in long-acting (LA) modalities for human immunodeficiency virus (HIV) treatment and prevention. Recent findings: LA injectable antiretroviral therapy (ART) has been approved in the United States, Canada and Europe; the United States also has approved LA injectable preexposure prophylaxis (PrEP) and the World Health Organization has recommended the vaginal PrEP ring. Current LA PrEP modalities in clinical trials include injections, films, rings, and implants; LA ART modalities in trials include subcutaneous injections and long-term oral pills. Although LA modalities hold incredible promise, global availability is inhibited by long-standing multilevel perils including declining multilateral funding, patent protections and lack of political will. Once available, access and uptake are limited by factors s…
matched on optimism (text), hope (text)
Natural disasters and mental health.
Natural disasters are large-scale adverse events resulting from natural processes of the earth, often associated with death, trauma, and destruction of property. They threaten harm or death to a large group of people; cause disruption of services and social networks and a communal loss of resources; and involve identifiable mental and physical health outcomes, among those affected. While majority of individuals who experience a traumatic event due to natural disasters do not develop psychopathology, natural disasters can threaten our psychological well-being in many ways and they can result in both short and long-term psychological distress and thus create a significant burden of mental health conditions on individuals and the community affected by them. In this paper we provide a narrative review that focuses on the mental health effects of natural disasters. We discuss effective, evide…
matched on optimism (text), hope (text)
A Systematic Mixed-Studies Review of Hope Experiences in Parents of Children With Cancer.
Background: Hope is negatively associated with parental psychosocial distress and psychological maladjustment as well as an important aspect of emotional well-being and coping for adults with cancer and their caregivers. Yet, little is known about hope experiences of parents of children with cancer. Objective: The aim of this study was to comprehensively describe hope experiences in parents of children with cancer using a systematic mixed-studies review. Intervention/methods: Psych INFO, PubMed, Academic Search Premier, and CINAHL databases were used to retrieve articles published in English between January 2005 and October 2019. Using the systematic mixed-studies review convergent design, qualitative and quantitative data were collected and extracted followed by qualitative synthesis. Seventeen articles met the inclusion criteria. Exclusion criteria were systematic reviews, nonresearch …
matched on optimism (text), hope (text)
Cognitive Aging and the Promise of Physical Activity.
Is the field of cognitive aging irretrievably concerned with decline and deficits, or is it shifting to emphasize the hope of preservation and enhancement of cognitive function in late life? A fragment of an answer comes from research attempting to understand the reasons for individual variability in the extent and rate of cognitive decline. This body of work has created a sense of optimism based on evidence that there are some health behaviors that amplify cognitive performance or mitigate the rate of age-related cognitive decline. In this context, we discuss the role of physical activity on neurocognitive function in late adulthood and summarize how it can be conceptualized as a constructive approach both for the maintenance of cognitive function and as a therapeutic for enhancing or optimizing cognitive function in late life. In this way, physical activity research can be used to shap…
matched on optimism (text), hope (text)
Any closer to successful therapy of multiple myeloma? CAR-T cell is a good reason for optimism.
Despite many recent advances on cancer novel therapies, researchers have yet a long way to cure cancer. They have to deal with tough challenges before they can reach success. Nonetheless, it seems that recently developed immunotherapy-based therapy approaches such as adoptive cell transfer (ACT) have emerged as a promising therapeutic strategy against various kinds of tumors even the cancers in the blood (liquid cancers). The hematological (liquid) cancers are hard to be targeted by usual cancer therapies, for they do not form localized solid tumors. Until recently, two types of ACTs have been developed and introduced; tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR)-T cells which the latter is the subject of our discussion. It is interesting about engineered CAR-T cells that they are genetically endowed with unique cancer-specific characteristics, so they can us…
matched on optimism (text), hope (text)
A community perspective of COVID-19 and obesity in children: Causes and consequences.
The pandemic of childhood obesity that has been increasing over the last decade has collided with the current pandemic of COVID-19. Enforced behavioural changes have resulted in a myriad of problems for children particularly in weight management. Restricted activity is the most obvious but many other aspects of life have exacerbated biological, psychosocial, and behavioral factors identified as risks for childhood obesity. Significant effort is required to turn around the prevailing tide of weight gain necessitating changes in personal and family behavior and diet, as well as high-level governmental and educational policy. Evidence-based, focused, long-term interventions which are adequately funded are required. Enthusiasm and optimism for change coupled with public engagement by utilization of new technology as well as traditional methods offers hope for change. Public health interventi…
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Drugging the "Undruggable" MYCN Oncogenic Transcription Factor: Overcoming Previous Obstacles to Impact Childhood Cancers.
Effective treatment of pediatric solid tumors has been hampered by the predominance of currently "undruggable" driver transcription factors. Improving outcomes while decreasing the toxicity of treatment necessitates the development of novel agents that can directly inhibit or degrade these elusive targets. MYCN in pediatric neural-derived tumors, including neuroblastoma and medulloblastoma, is a paradigmatic example of this problem. Attempts to directly and specifically target MYCN have failed due to its similarity to MYC, the unstructured nature of MYC family proteins in their monomeric form, the lack of an understanding of MYCN-interacting proteins and ability to test their relevance in vivo, the inability to obtain structural information on MYCN protein complexes, and the challenges of using traditional small molecules to inhibit protein-protein or protein-DNA interactions. However, t…
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The State of Our Understanding of the Pathophysiology and Optimal Treatment of Depression: Glass Half Full or Half Empty?
Major depressive disorder is a remarkably common and often severe psychiatric disorder associated with high levels of morbidity and mortality. Patients with major depression are prone to several comorbid psychiatric conditions, including posttraumatic stress disorder, anxiety disorders, obsessive-compulsive disorder, and substance use disorders, and medical conditions, including cardiovascular disease, diabetes, stroke, cancer, which, coupled with the risk of suicide, result in a shortened life expectancy. The goal of this review is to provide an overview of our current understanding of major depression, from pathophysiology to treatment. In spite of decades of research, relatively little is known about its pathogenesis, other than that risk is largely defined by a combination of ill-defined genetic and environmental factors. Although we know that female sex, a history of childhood maltr…
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The special considerations of gene therapy for mitochondrial diseases.
The recent success of gene therapy across multiple clinical trials has inspired a great deal of hope regarding the treatment of previously intractable genetic diseases. This optimism has been extended to the prospect of gene therapy for mitochondrial disorders, which are not only particularly severe but also difficult to treat. However, this hope must be tempered by the reality of the mitochondrial organelle, which possesses specific biological properties that complicate genetic manipulation. In this perspective, we will discuss some of these complicating factors, including the unique pathways used to express and import mitochondrial proteins. We will also present some ways in which these challenges can be overcome by genetic manipulation strategies tailored specifically for mitochondrial diseases.
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Parkinson's disease: etiopathogenesis and treatment.
The concept of 'idiopathic' Parkinson's disease (PD) as a single entity has been challenged with the identification of several clinical subtypes, pathogenic genes and putative causative environmental agents. In addition to classic motor symptoms, non-motor manifestations (such as rapid eye movement sleep disorder, anosmia, constipation and depression) appear at prodromic/premotor stage and evolve, along with cognitive impairment and dysautonomia, as the disease progresses, often dominating the advanced stages of the disease. The key molecular pathogenic mechanisms include α-synuclein misfolding and aggregation, mitochondrial dysfunction, impairment of protein clearance (associated with deficient ubiquitin-proteasome and autophagy-lysosomal systems), neuroinflammation and oxidative stress. The involvement of dopaminergic as well as noradrenergic, glutamatergic, serotonergic and adenosine …
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Countering Gram-Negative Antibiotic Resistance: Recent Progress in Disrupting the Outer Membrane with Novel Therapeutics.
Gram-negative bacteria shield themselves from antibiotics by producing an outer membrane (OM) that forms a formidable permeability barrier. Multidrug resistance among these organisms is a particularly acute problem that is exacerbated by the OM. The poor penetrance of many available antibiotics prevents their clinical use, and efforts to discover novel classes of antibiotics against Gram-negative bacteria have been unsuccessful for almost 50 years. Recent insights into how the OM is built offer new hope. Several essential multiprotein molecular machines (Bam, Lpt, and Lol) work in concert to assemble the barrier and offer a swathe of new targets for novel therapeutic development. Murepavadin has been at the vanguard of these efforts, but its recently reported phase III clinical trial toxicity has tempered the anticipation of imminent new clinical options. Nonetheless, the many concerted …
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Management of NK/T-Cell Lymphoma, Nasal Type.
Extranodal natural killer (NK)/T-cell lymphoma, nasal type, is a rare peripheral T-cell lymphoma associated with Epstein-Barr virus. It most often presents as limited-stage disease in patients of East Asian descent with a palatal deformity caused by erosion of the tumor through the hard palate. Limited-stage disease is often curable with the use of l-asparaginase-based chemotherapy and high-dose radiation therapy. Obtaining an accurate diagnosis is essential, because treatment with standard lymphoma regimens and omission of radiation severely compromise the likelihood of long-term survival. Conversely, patients with advanced disease have a poor prognosis and are recommended for asparaginase-based chemotherapy followed by consolidation with autologous transplantation as a potentially curative approach. Progress often has been hampered by the rarity of this disease. However, discovery of c…
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Drugs in Development for Acute Kidney Injury.
The care of patients with acute kidney injury (AKI) has been limited due to the lack of effective therapeutics that can either prevent AKI during high-risk situations or treat AKI once established. A revolution in the scientific understanding of the pathogenesis of AKI has led to the identification of potential therapeutic targets. These targets include pathways involved in inflammation, cellular repair and fibrosis, cellular metabolism and mitochondrial function, oxidative stress, apoptosis, and hemodynamics and oxygen delivery. Many compounds are entering early-phase clinical trials. In addition, efforts to better describe sub-categories of AKI (through endo-phenotyping) hold promise to target therapies more effectively based upon pathways that are operative in the pathogenesis. These advances bring optimism that the care of patients with AKI will be transformed with the hope of better…
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Conceptualizations, assessments, and implications of personal recovery in mental illness: A scoping review of systematic reviews and meta-analyses.
Objective: Recovery, defined as a personal process of living with mental illness, has become a prominent concept in mental health care. We aimed to map the state of the art of conceptualizing recovery, its promoting and impeding factors, recovery-oriented practice, and the assessment of recovery. Method: A scoping review of systematic reviews and meta-analyses was performed. Systematic searches were conducted, supplemented with hand-searching in reference lists. Results: Of 228 articles that were identified and 33 that were reviewed, a total of 25 were included. This review showed that the CHIME conceptual framework for personal recovery is widely endorsed, containing the elements of connectedness, hope and optimism, identity, meaning in life, and empowerment. Although personal recovery first and foremost starts from individual preferences, the CHIME framework should be adapted according…
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The Flowering of Positive Psychology in Foreign Language Teaching and Acquisition Research.
The present contribution offers an overview of a new area of research in the field of foreign language acquisition, which was triggered by the introduction of Positive Psychology (PP) (MacIntyre and Gregersen, 2012). For many years, a cognitive perspective had dominated research in applied linguistics. Around the turn of the millennium researchers became increasingly interested in the role of emotions in foreign language learning and teaching, beyond established concepts like foreign language anxiety and constructs like motivation and attitudes toward the foreign language. As a result, a more nuanced understanding of the role of positive and negative learner and teacher emotions emerged, underpinned by solid empirical research using a wide range of epistemological and methodological approaches. PP interventions have been carried out in schools and universities to strengthen learners and …
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Regeneration of Spinal Cord Connectivity Through Stem Cell Transplantation and Biomaterial Scaffolds.
Significant progress has been made in the treatment of spinal cord injury (SCI). Advances in post-trauma management and intensive rehabilitation have significantly improved the prognosis of SCI and converted what was once an "ailment not to be treated" into a survivable injury, but the cold hard fact is that we still do not have a validated method to improve the paralysis of SCI. The irreversible functional impairment of the injured spinal cord is caused by the disruption of neuronal transduction across the injury lesion, which is brought about by demyelination, axonal degeneration, and loss of synapses. Furthermore, refractory substrates generated in the injured spinal cord inhibit spontaneous recovery. The discovery of the regenerative capability of central nervous system neurons in the proper environment and the verification of neural stem cells in the spinal cord once incited hope th…
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The challenge of modulating β-cell autoimmunity in type 1 diabetes.
With the conceptual advance about four decades ago that type 1 diabetes represents an autoimmune disease, hope arose that immune-based therapies would soon emerge to prevent and reverse the disorder. However, despite dozens of clinical trials seeking to achieve these goals, the promise remains unfulfilled, at least in a pragmatic form. With the benefit of hindsight, several important reasons are likely to account for this disappointing outcome, including failure to appreciate disease heterogeneity, inappropriate use of rodent models of disease, inadequacies in addressing the immunological and metabolic contributions to the disease, suboptimal trial designs, and lack of a clear understanding of the pathogenesis of type 1 diabetes. In this Series paper, we convey how recent knowledge gains in these areas, combined with efforts related to disease staging and emerging mechanistic data from c…
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The future of rodent models in depression research.
Currently, over 300 million people worldwide have depression, and the socioeconomic burden of this debilitating disorder is anticipated to increase markedly over the coming decades against a background of increasing global turmoil. Despite this impending crisis, we are still waiting for improved therapeutic options for this disorder to emerge, which has led to increasing criticism of the role and value of preclinical models of depression. In this Review, we examine this landscape, focusing firstly on issues related to the terminology used in this context and the myriad of preclinical approaches to modelling and assaying aspects of depression in rodents. We discuss the importance of sex as a biological variable and the controversial idea of intergenerational and transgenerational transmission of depressive-like traits. We then examine the technical strategies available to dissect these mo…
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Emerging role of the P2X7-NLRP3-IL1β pathway in mood disorders.
The science of neuroimmunopsychiatry has evolved rapidly in the last few years with the hope of tackling the unmet need in mood disorders. This article focuses on an inflammatory pathway, highly conserved in myeloid cells that may play a role in neuroinflammatory disorders including depression. Within the brain tissue, microglia are the myeloid cells that express the P2X7 ion channel that is connected through the NLRP3 inflammasome complex leading to release of IL-1β and IL-18. We present, in the way of reviewing relevant literature, the preclinical data and scientific rationale supporting the role of the P2X7-NLRP3-IL-1β pathway in mood disorders. We also highlight recent advances in drug discovery and development of P2X7 small molecule antagonists and P2X7 PET ligands which provide optimism that clinical tools are availableto address critical proof-of-concept experiments in mood disord…
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Positive psychology perspective on traumatic brain injury recovery and rehabilitation.
Recovery from traumatic brain injury (TBI) is heterogeneous, with injury characteristics and neuropathological findings accounting for a relatively modest proportion of the variance in clinical outcome. Furthermore, premorbid personality traits and psychological characteristics may moderate psychosocial recovery. Constructs from the field of positive psychology have been examined in multiple illness populations and are increasingly gaining attention as factors that may influence recovery from TBI. Positive affect, hope, optimism, adaptive coping style, and resilience have all been examined in the context of TBI. These phenomena are of particular interest because they may inform treatment, either by reducing psychological distress and promoting better adjustment, or by augmenting existing therapies to improve engagement. In general, research suggests that higher levels of these factors pr…
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A Singular Hope: How the Discussion Around Cancer Surgery Sometimes Fails.
Background: Patients with cancer often have an overly optimistic view of prognosis, as well as potential benefits of treatment. Patient-surgeon communication in the preoperative period has not received as much attention as communicating prognosis or bad news in the postoperative setting. Methods: The published literature on patient-physician communication in the preoperative setting among patients considering surgery for a malignant indication was reviewed. PubMed was queried for MESH terms including "surgery," "preoperative," "discussion," "treatment goals," "patient perceptions," and "cure." Information on how surgeons and patients may be empowered to improve communication about goals of care was also outlined. Results: Physicians tended not to dwell on prognosis in early discussions, instead emphasizing the uniqueness of individuals and the uncertainty of statistics. The treatment pla…
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