Stress physiology and inflammation

وَنُوحًا إِذۡ نَادَىٰ مِن قَبۡلُ فَٱسۡتَجَبۡنَا لَهُۥ فَنَجَّيۡنَٰهُ وَأَهۡلَهُۥ مِنَ ٱلۡكَرۡبِ ٱلۡعَظِيمِ

Long before that, We answered Noah when he cried out to Us: We saved him and his family from the great calamity

وَنَجَّيۡنَٰهُمَا وَقَوۡمَهُمَا مِنَ ٱلۡكَرۡبِ ٱلۡعَظِيمِ

We saved them and their people from great distress

وَنَجَّيۡنَٰهُ وَأَهۡلَهُۥ مِنَ ٱلۡكَرۡبِ ٱلۡعَظِيمِ

We saved him and his people from great distress

قُلِ ٱللَّهُ يُنَجِّيكُم مِّنۡهَا وَمِن كُلِّ كَرۡبࣲ ثُمَّ أَنتُمۡ تُشۡرِكُونَ

Say, ‘God rescues you from this and every distress; yet still you worship others beside Him.’

وَلَمَّا بَلَغَ أَشُدَّهُۥٓ ءَاتَيۡنَٰهُ حُكۡمࣰ ا وَعِلۡمࣰ اۚ وَكَذَٰلِكَ نَجۡزِي ٱلۡمُحۡسِنِينَ

When he reached maturity, We gave him judgement and knowledge: this is how We reward those who do good

وَلَا تَقۡرَبُواْ مَالَ ٱلۡيَتِيمِ إِلَّا بِٱلَّتِي هِيَ أَحۡسَنُ حَتَّىٰ يَبۡلُغَ أَشُدَّهُۥۚ وَأَوۡفُواْ ٱلۡكَيۡلَ وَٱلۡمِيزَانَ بِٱلۡقِسۡطِۖ لَا نُكَلِّفُ نَفۡسًا إِلَّا وُسۡعَهَاۖ وَإِذَا قُلۡتُمۡ فَٱعۡدِلُواْ وَلَوۡ كَانَ ذَا قُرۡبَىٰۖ وَبِعَهۡدِ ٱللَّهِ أَوۡفُواْۚ ذَٰلِكُمۡ وَصَّىٰكُم بِهِۦ لَعَلَّكُمۡ تَذَكَّرُونَ

Stay well away from the property of orphans, except with the best [intentions], until they come of age; give full measure and weight, according to justice’- We do not burden any soul with more than it can bear- ‘ when you speak, be just, even if it concerns a relative; keep any promises you make in God’s name. This is what He commands you to do, so that you may take heed’

And mention Noah what follows Nūhan substitutes for it when he called when he supplicated to God against his people — with the words My Lord do not leave upon the earth any inhabitant from among the disbelievers … to the end of the verse Q. 7126 before that is before the time of Abraham and Lot. And We responded to him and delivered him and his people who were in the Ark with him from the great agony namely from drowning and his people’s denial of him.

and We delivered them and their people the Children of Israel from the great distress namely Pharaoh’s enslavement of them.

And We delivered him and his family from the great distress which was the drowning

And (remember) Nuh, when he cried (to Us) aforetime. We answered to his invocation and saved him and his family from the great distress (76)We helped him against the people who denied Our Ayat. Verily, they were a people given to evil. So We drowned them all (77) Nuh and His People Allah tells us how He responded to His servant and Messenger Nuh, peace be upon him, when he prayed to Him against his people for their disbelief in him: فَدَعَا رَبَّهُ أَنِّي مَغْلُوبٌ فَانتَصِرْ (Then he invoked his Lord (saying): "I have been overcome, so help (me)!")(54:10) وَقَالَ نُوحٌ رَّبِّ لَا تَذَرْ عَلَى الْأَرْضِ مِنَ الْكَافِرِينَ دَيَّارًا - إِنَّكَ إِن تَذَرْهُمْ يُضِلُّوا عِبَادَكَ وَلَا يَلِدُوا إِلَّا فَاجِرًا كَفَّارًا (And Nuh said: "My Lord! Leave not any inhabitant of the disbelievers on the earth! If You leave them, they will mislead Your servants, and they will beget none but wic

And, indeed We gave Our grace to Musa and Harun (114)And We saved them and their people from the great distress (115)And helped them, so that they became the victors (116)And We gave them the clear Scripture (117)And guided them to the right path (118)And We left for them among the later generations (119)"Salam (peace!) be upon Musa and Harun! (120)Verily, thus do We reward the doers of good (121)Verily, they were two of Our believing servants (122) Musa and Harun Allah tells us how He blessed Musa and Harun with prophethood and how He saved them, along with those who believed, from the oppression of Fir'awn and his people, who had persecuted them by killing their sons and sparing their women, and by forcing them to do the most menial tasks, then ultimately He caused them to prevail over them and to seize their lands and their wealth and all that they had spent their entire lives amass

And indeed Nuh invoked Us, and We are the best of those who answer (75)And We rescued him and his family from the great distress (76)And, his progeny, them We made the survivors (77)And left for him (a goodly remembrance) among the later generation (78)"Salam (peace!) be upon Nuh among the all creatures! (79)Verily, thus We reward the gooddoers (80)Verily, he [Nuh] was one of Our believing servants (81)Then We drowned the others (82) Nuh and His People When Allah tells us about how most of the early people went astray from the path of salvation, He starts the detailed explanation of that with the story of Nuh and the rejection of his people. Only a few of Nuh's people believed in him, despite the long period of time he spent among them. He stayed among them for one thousand years less fifty, and after he stayed among them for so long and their disbelief became too much for him to bear

حَدَّثَنِي عَبْدُ اللَّهِ بْنُ مُحَمَّدٍ، حَدَّثَنَا عَبْدُ الْمَلِكِ بْنُ عَمْرٍو، حَدَّثَنَا زُهَيْرُ بْنُ مُحَمَّدٍ، عَنْ مُحَمَّدِ بْنِ عَمْرِو بْنِ حَلْحَلَةَ، عَنْ عَطَاءِ بْنِ يَسَارٍ، عَنْ أَبِي سَعِيدٍ الْخُدْرِيِّ، وَعَنْ أَبِي هُرَيْرَةَ، عَنِ النَّبِيِّ صلى الله عليه وسلم قَالَ ‏ "‏ مَا يُصِيبُ الْمُسْلِمَ مِنْ نَصَبٍ وَلاَ وَصَبٍ وَلاَ هَمٍّ وَلاَ حُزْنٍ وَلاَ أَذًى وَلاَ غَمٍّ حَتَّى الشَّوْكَةِ يُشَاكُهَا، إِلاَّ كَفَّرَ اللَّهُ بِهَا مِنْ خَطَايَاهُ ‏"‏‏.‏

Narrated Abu Sa`id Al-Khudri and Abu Huraira:The Prophet (ﷺ) said, "No fatigue, nor disease, nor sorrow, nor sadness, nor hurt, nor distress befalls a Muslim, even if it were the prick he receives from a thorn, but that Allah expiates some of his sins for that

حَدَّثَنَا إِبْرَاهِيمُ بْنُ الْمُنْذِرِ، قَالَ حَدَّثَنِي مُحَمَّدُ بْنُ فُلَيْحٍ، قَالَ حَدَّثَنِي أَبِي، عَنْ هِلاَلِ بْنِ عَلِيٍّ، مِنْ بَنِي عَامِرِ بْنِ لُؤَىٍّ عَنْ عَطَاءِ بْنِ يَسَارٍ، عَنْ أَبِي هُرَيْرَةَ ـ رضى الله عنه ـ قَالَ قَالَ رَسُولُ اللَّهِ صلى الله عليه وسلم ‏ "‏ مَثَلُ الْمُؤْمِنِ كَمَثَلِ الْخَامَةِ مِنَ الزَّرْعِ مِنْ حَيْثُ أَتَتْهَا الرِّيحُ كَفَأَتْهَا، فَإِذَا اعْتَدَلَتْ تَكَفَّأُ بِالْبَلاَءِ، وَالْفَاجِرُ كَالأَرْزَةِ صَمَّاءَ مُعْتَدِلَةً حَتَّى يَقْصِمَهَا اللَّهُ إِذَا شَاءَ ‏"‏‏.‏

Narrated Abu Huraira:Allah's Messenger (ﷺ) said, "The example of a believer is that of a fresh tender plant; from whatever direction the wind comes, it bends it, but when the wind becomes quiet, it becomes straight again. Similarly, a believer is afflicted with calamities (but he remains patient till Allah removes his difficulties.) And an impious wicked person is like a pine tree which keeps hard and straight till Allah cuts (breaks) it down when He wishes." (See Hadith No. 558, Vol)

حَدَّثَنَا مُحَمَّدُ بْنُ يَحْيَى، قال حَدَّثَنَا إِسْحَاقُ بْنُ مُحَمَّدٍ الْفَرْوِيُّ، قال حَدَّثَنَا إِسْمَاعِيلُ بْنُ جَعْفَرٍ، عَنْ عُمَارَةَ بْنِ غَزِيَّةَ، عَنْ عَاصِمِ بْنِ عُمَرَ بْنِ قَتَادَةَ، عَنْ مَحْمُودِ بْنِ لَبِيدٍ، عَنْ قَتَادَةَ بْنِ النُّعْمَانِ، أَنَّ رَسُولَ اللَّهِ صلى الله عليه وسلم قَالَ ‏ "‏ إِذَا أَحَبَّ اللَّهُ عَبْدًا حَمَاهُ الدُّنْيَا كَمَا يَظَلُّ أَحَدُكُمْ يَحْمِي سَقِيمَهُ الْمَاءَ ‏"‏ ‏.‏ قَالَ أَبُو عِيسَى وَفِي الْبَابِ عَنْ صُهَيْبٍ وَأُمِّ الْمُنْذِرِ ‏.‏ وَهَذَا حَدِيثٌ حَسَنٌ غَرِيبٌ ‏.‏ وَقَدْ رُوِيَ هَذَا الْحَدِيثُ عَنْ مَحْمُودِ بْنِ لَبِيدٍ عَنِ النَّبِيِّ صلى الله عليه وسلم مُرْسَلاً ‏.‏ حَدَّثَنَا عَلِيُّ بْنُ حُجْرٍ، قال أَخْبَرَنَا إِسْمَاعِيلُ بْنُ جَعْفَرٍ، عَنْ عَمْرِو بْنِ أَبِي عَمْرٍو، عَنْ عَاصِمِ بْنِ عُمَرَ بْنِ قَتَادَةَ، عَنْ مَحْمُودِ بْنِ لَبِيدٍ، عَنِ النَّبِيِّ صلى الله عليه وسلم نَحْوَهُ وَلَمْ يَذْكُرْ فِيهِ عَنْ قَتَادَةَ بْنِ النُّعْمَانِ ‏.‏ قَالَ أَبُو عِيسَى وَقَتَادَةُ بْنُ النُّعْمَانِ الظَّفَرِيُّ هُوَ أَخُو أَبِي سَعِيدٍ الْخُدْرِيِّ لأُمِّهِ وَمَحْمُودُ بْنُ لَبِيدٍ قَدْ أَدْرَكَ النَّبِيَّ صلى الله عليه وسلم وَرَآهُ وَهُوَ غُلاَمٌ صَغِيرٌ ‏.‏

Qatadah bin An-Nu'man narrated that the Messenger of Allah (s.a.w) said:"When Allah loves a slave, He prevents him from the world, just as one of you prevents his sick from water." Another chain reports a similar narration

حَدَّثَنَا عَبَّاسُ بْنُ مُحَمَّدٍ الدُّورِيُّ، قال حَدَّثَنَا يُونُسُ بْنُ مُحَمَّدٍ، قال حَدَّثَنَا فُلَيْحُ بْنُ سُلَيْمَانَ، عَنْ عُثْمَانَ بْنِ عَبْدِ الرَّحْمَنِ التَّيْمِيِّ، عَنْ يَعْقُوبَ بْنِ أَبِي يَعْقُوبَ، عَنْ أُمِّ الْمُنْذِرِ، قَالَتْ دَخَلَ عَلَىَّ رَسُولُ اللَّهِ صلى الله عليه وسلم وَمَعَهُ عَلِيٌّ وَلَنَا دَوَالٍ مُعَلَّقَةٌ قَالَتْ فَجَعَلَ رَسُولُ اللَّهِ صلى الله عليه وسلم يَأْكُلُ وَعَلِيٌّ مَعَهُ يَأْكُلُ ‏.‏ فَقَالَ رَسُولُ اللَّهِ صلى الله عليه وسلم لِعَلِيٍّ ‏"‏ مَهْ مَهْ يَا عَلِيُّ فَإِنَّكَ نَاقِهٌ ‏"‏ ‏.‏ قَالَ فَجَلَسَ عَلِيٌّ وَالنَّبِيُّ صلى الله عليه وسلم يَأْكُلُ ‏.‏ قَالَتْ فَجَعَلْتُ لَهُمْ سِلْقًا وَشَعِيرًا فَقَالَ النَّبِيُّ صلى الله عليه وسلم ‏"‏ يَا عَلِيُّ مِنْ هَذَا فَأَصِبْ فَإِنَّهُ أَوْفَقُ لَكَ ‏"‏ ‏.‏ قَالَ أَبُو عِيسَى هَذَا حَدِيثٌ حَسَنٌ غَرِيبٌ لاَ نَعْرِفُهُ إِلاَّ مِنْ حَدِيثِ فُلَيْحٍ ‏.‏ وَيُرْوَى عَنْ فُلَيْحٍ عَنْ أَيُّوبَ بْنِ عَبْدِ الرَّحْمَنِ ‏.‏ حَدَّثَنَا مُحَمَّدُ بْنُ بَشَّارٍ، قال حَدَّثَنَا أَبُو عَامِرٍ، وَأَبُو دَاوُدَ قَالاَ حَدَّثَنَا فُلَيْحُ بْنُ سُلَيْمَانَ، عَنْ أَيُّوبَ بْنِ عَبْدِ الرَّحْمَنِ، عَنْ يَعْقُوبَ، عَنْ أُمِّ الْمُنْذِرِ الأَنْصَارِيَّةِ، فِي حَدِيثِهِ قَالَتْ دَخَلَ عَلَيْنَا رَسُولُ اللَّهِ صلى الله عليه وسلم فَذَكَرَ نَحْوَ حَدِيثِ يُونُسَ بْنِ مُحَمَّدٍ إِلاَّ أَنَّهُ قَالَ ‏"‏ أَنْفَعُ لَكَ ‏"‏ ‏.‏ وَقَالَ مُحَمَّدُ بْنُ بَشَّارٍ وَحَدَّثَنِيهِ أَيُّوبُ بْنُ عَبْدِ الرَّحْمَنِ ‏.‏ هَذَا حَدِيثٌ جَيِّدٌ غَرِيبٌ ‏.‏

Umm Al-Mundhir said:"The Messenger of Allah (ﷺ) entered upon me, while `Ali was with him, and we had a cluster of unripe dates hanging." She said: "The Messenger of Allah (ﷺ) began eating, and `Ali ate with him. The Messenger of Allah (ﷺ) said to `Ali: 'Stop, stop, for you are still recovering.' So `Ali sat and the Prophet (ﷺ) ate." She said: "I made some chard and barley for them, so the Prophet (ﷺ) said: 'O `Ali eat from this, for indeed it will be more suitable for you." Another chain reports a similar narration

62 الثالث عن ابن عباس رضي الله عنهما قال كنت خلف النبي صلى الله عليه وسلم يوما فقال يا غلام إني أعلمك كلمات احفظ الله يحفظك احفظ الله تجده تجاهك إذا سألت فاسأل الله وإذا استعنت فاستعن بالله واعلم أن الأمة لو اجتمعت على أن ينفعوك بشيء لم ينفعوك إلا بشيء قد كتبه الله لك وإن اجتمعوا على أن يضروك بشيء لم يضروك إلا بشيء قد كتبه الله عليك رفعت الأقلام وجفت الصحف رواه الترمذي وقال حديث حسن صحيح وفي رواية غير الترمذي احفظ الله تجده أمامك تعرف إلى الله في الرخاء يعرفك في الشدة واعلم أن ما أخطأك لم يكن ليصيبك وما أصابك لم يكن ليخطئك واعلم أن النصر مع الصبر وأن الفرج مع الكرب وأن مع العسر يسرا

التاسعة والخمسون ان ذكر الله عز وجل يسهل الصعب وييسر العسير ويخفف المشاق فما ذكر الله عز وجل على صعب الا هان ولا على عسير الا تيسر ولا مشقة الا خفت ولا شدة الا زالت ولا كربه الا انفرجت فذكر الله تعالى هو الفرج بعد الشدة واليسر بعد العسر والفرج بعد الغم والهم يوضحه

وقالت أسماء بنت عميس : علمني رسول اللهكلمات أقولها عند الكرب : الله الله ربي لا أشرك به شيئا

التنفيس هو الترويح يقال نفس الله عنك الكرب أي اراحك منه وفي الحديث الصحيح من نفس عن مؤمن كربة من كرب الدنيا نفس الله عنه كربة من كرب يوم القيامة

وفى "صحيح البخاري" من حديث أنس رضي الله عنه قال: لما ثقل النبي صلى الله عليه وآله وسلم، جعل يتغشاه الكرب، فقالت فاطمة رضي الله عنها: واكرب أبتاه! فقال لها: "ليس على أبيك كرب بعد اليوم".

خليلي ما من ساعة تذكرانها % من الدهر إلا فرجت عني الكربا

Disruption of multisystem responses to stress in type 2 diabetes: investigating the dynamics of allostatic load.: Psychological stress-related processes are thought to contribute to the development and progression of type 2 diabetes, but the biological mechanisms involved are poorly understood. Here, we tested the notion that people with type 2 diabetes experience chronic allostatic load, manifest as dynamic disturbances in reactivity to and recovery from stress across multiple (cardiovascular, neuroendocrine, inflammatory, metabolic) biological systems, coupled with heightened experience of chronic life st

The influences of vitamin D and omega-3 co-supplementation on clinical, metabolic and genetic parameters in women with polycystic ovary syndrome.: Objective: The aim of this study was to evaluate the effect of the co-administration of vitamin D and omega-3 fatty acid on clinical, metabolic and genetic parameters in women with polycystic ovary syndrome (PCOS). Methods: This randomized, double-blinded, placebo-controlled clinical trial was conducted on 60 subjects, aged 18-40 years old with PCOS. Subjects were randomly allocated to take either 50,000 IU vitamin D every 2 weeks plus 2000 mg/day omega-3 fatty acid from fish oil (n = 30) or pla

The effect of Nigella sativa (black seed) on biomarkers of inflammation and oxidative stress: an updated systematic review and meta-analysis of randomized controlled trials.: Objective: This study was conducted to assess the effect of Nigella sativa (N. sativa) supplementation on inflammatory and oxidative markers among the adult population. Methods: We carried out a comprehensive, systematic search of Scopus, Embase, Cochrane Library, Web of Science, PubMed, and Google Scholar till December 2022. A random-effects model was used to estimate the overall effect size. Results: In total, twenty trials consisting of 1086 participants were included in the meta-analysis. Fi

Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder.: Cumulative meta-analyses are used to evaluate the extent to which further studies are needed to confirm or refute a hypothesis. We used this approach to assess observational evidence on systemic inflammation in individuals with major depressive disorder. We identified 58 studies of four common inflammatory markers in a literature search of PubMed, Embase and PsychInfo databases in May 2014. Pooled data from the earliest eight studies already showed an association between interleukin-6 concentrat

Towards a consensus definition of allostatic load: a multi-cohort, multi-system, multi-biomarker individual participant data (IPD) meta-analysis.: Background: Allostatic load (AL) is a multi-system composite index for quantifying physiological dysregulation caused by life course stressors. For over 30 years, an extensive body of research has drawn on the AL framework but has been hampered by the lack of a consistent definition. Methods: This study analyses data for 67,126 individuals aged 40-111 years participating in 13 different cohort studies and 40 biomarkers across 12 physiological systems: hypothalamic-pituitary-adrenal (HPA) axis, s

Cytokines and C-reactive protein alterations with respect to cognitive impairment in schizophrenia and bipolar disorder: A systematic review.: Background: The aim of this article was to perform a systematic review of studies investigating the association between peripheral levels of cytokines and C-reactive protein (CRP), cytokine gene polymorphisms and cognition in patients with schizophrenia and bipolar disorder (BD). Methods: The following databases: PubMed, CINAHL Complete, Academic Search Complete, ERIC and Health Source: Nursing/Academic Edition databases were searched according to the PRISMA guidelines. We included studies that

Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats.

Background and aims: Intestinal barrier impairment is incriminated in the pathophysiology of intestinal gut disorders associated with psychiatric comorbidity. Increased intestinal permeability associated with upload of lipopolysaccharides (LPS) translocation induces depressive symptoms. Gut microbiota and probiotics alter behavior and brain neurochemistry. Since Lactobacillus farciminis suppresses stress-induced hyperpermeability, we examined whether (i) L. farciminis affects the HPA axis stress response, (ii) stress induces changes in LPS translocation and central cytokine expression which may be reversed by L. farciminis, (iii) the prevention of "leaky" gut and LPS upload are involved in these effects. Methods: At the end of the following treatments female rats were submitted to a partial restraint stress (PRS) or sham-PRS: (i) oral administration of L. farciminis during 2 weeks, (ii) …

matched on Inflammation (mesh), Cytokines (mesh)

Leukocyte telomere length in major depression: correlations with chronicity, inflammation and oxidative stress--preliminary findings.

Background: Depression is associated with an unusually high rate of aging-related illnesses and early mortality. One aspect of "accelerated aging" in depression may be shortened leukocyte telomeres. When telomeres critically shorten, as often occurs with repeated mitoses or in response to oxidation and inflammation, cells may die. Indeed, leukocyte telomere shortening predicts early mortality and medical illnesses in non-depressed populations. We sought to determine if leukocyte telomeres are shortened in Major Depressive Disorder (MDD), whether this is a function of lifetime depression exposure and whether this is related to putative mediators, oxidation and inflammation. Methodology: Leukocyte telomere length was compared between 18 unmedicated MDD subjects and 17 controls and was correlated with lifetime depression chronicity and peripheral markers of oxidation (F2-isoprostane/Vitamin…

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Intermittent hypoxia exacerbates metabolic effects of diet-induced obesity.

Obesity causes insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD), but the relative contribution of sleep apnea is debatable. The main aim of this study is to evaluate the effects of chronic intermittent hypoxia (CIH), a hallmark of sleep apnea, on IR and NAFLD in lean mice and mice with diet-induced obesity (DIO). Mice (C57BL/6J), 6-8 weeks of age were fed a high fat (n = 18) or regular (n = 16) diet for 12 weeks and then exposed to CIH or control conditions (room air) for 4 weeks. At the end of the exposure, fasting (5 h) blood glucose, insulin, homeostasis model assessment (HOMA) index, liver enzymes, and intraperitoneal glucose tolerance test (1 g/kg) were measured. In DIO mice, body weight remained stable during CIH and did not differ from control conditions. Lean mice under CIH were significantly lighter than control mice by day 28 (P = 0.002). Compared to lean mi…

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β2-Adrenoreceptors of regulatory lymphocytes are essential for vagal neuromodulation of the innate immune system.

The nervous system is classically organized into sympathetic and parasympathetic systems acting in opposition to maintain physiological homeostasis. Here, we report that both systems converge in the activation of β2-adrenoceptors of splenic regulatory lymphocytes to control systemic inflammation. Vagus nerve stimulation fails to control serum TNF levels in either β2-knockout or lymphocyte-deficient nude mice. Unlike typical suppressor CD25(+) cells, the transfer of CD4(+)CD25(-) regulatory lymphocytes reestablishes the anti-inflammatory potential of the vagus nerve and β2-agonists to control inflammation in both β2-knockout and nude mice. β2-Agonists inhibit cytokine production in splenocytes (IC(50)≈ 1 μM) and prevent systemic inflammation in wild-type but not in β2-knockout mice. β2-Agonists rescue wild-type mice from established polymicrobial peritonitis in a clinically relevant time …

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Dysregulation of inflammatory responses by chronic circadian disruption.

Circadian rhythms modulate nearly every mammalian physiological process. Chronic disruption of circadian timing in shift work or during chronic jet lag in animal models leads to a higher risk of several pathologies. Many of these conditions in both shift workers and experimental models share the common risk factor of inflammation. In this study, we show that experimentally induced circadian disruption altered innate immune responses. Endotoxemic shock induced by LPS was magnified, leading to hypothermia and death after four consecutive weekly 6-h phase advances of the light/dark schedule, with 89% mortality compared with 21% in unshifted control mice. This may be due to a heightened release of proinflammatory cytokines in response to LPS treatment in shifted animals. Isolated peritoneal macrophages harvested from shifted mice exhibited a similarly heightened response to LPS in vitro, ind…

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Systemic infection and delirium: when cytokines and acetylcholine collide.

Systemic infection and drugs with anticholinergic effects are well-recognised and prevalent risk factors for delirium in elderly people. Experimental findings and neuropathological observations suggest that activation of microglia is pivotal for mediation of the behavioural effects of systemic infections. The microglial response is usually regulated tightly, but defensive features could turn neurotoxic once microglial cells escape from cholinergic inhibition. A self-propelling neuroinflammatory reaction might follow, and this cascade could account for the strong association between delirium and long-term cognitive impairment and even dementia. Here, we propose a hypothetical model, suggesting that poor outcome after delirium can be averted in vulnerable elderly people by use of readily available drugs. Agents that either restore cholinergic control of microglia or directly inhibit neuroi…

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Role of neuropeptide, cytokine, and growth factor signaling in complex regional pain syndrome.

Objective: Complex regional pain syndrome (CRPS) patients exhibit multiorgan pathology and inflammatory changes after limb trauma. The objective of this study was to identify how neuro-cutaneous signaling is facilitated after fracture and examine how this altered signaling contributes to the development of CRPS-like changes in the injured limb. Design and methods: These studies used a rat tibia fracture model that reliably generates hindpaw warmth, edema, increased spontaneous protein extravasation, allodynia, unweighting, and periarticular bone loss, a symptom complex resembling the vascular, nociceptive, and bone sequelae observed in early CRPS. Substance P (SP)-evoked extravasation responses, EIA and PCR assays, and immunohistochemical techniques were used to evaluate post-fracture up-regulation of neuro-cutaneous inflammatory signaling. A SP NK1 receptor antagonist was used to inhibi…

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Association of high-sensitivity C-reactive protein with de novo major depression.

Background: Although there is cross-sectional evidence that changes in the immune system contribute to the pathophysiology of depression, longitudinal data capable of elucidating cause and effect relationships are lacking. Aims: We aimed to determine whether subclinical systemic inflammation, as measured by serum high-sensitivity C-reactive protein (hsCRP) concentration, is associated with an increased risk of de novo major depressive disorder. Method: Major depressive disorder was diagnosed using a clinical interview (SCID-I/NP). This is a retrospective cohort study; from a population-based sample of 1494 randomly selected women recruited at baseline during the period 1994-7, 822 were followed for a decade and provided measures of both exposure and outcome. Of these women, 644 (aged 20-84 years) had no prior history of depression at baseline and were eligible for analysis. Results: Duri…

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Leukocyte telomere length is associated with HDL cholesterol levels: The Bogalusa heart study.

Objective: This study examined the relationships of high-density lipoprotein cholesterol (HDL-C) with LTL and the rate of its shortening. Background: Diminished levels of HDL-C are associated with an increased risk for atherosclerosis. Shortened leukocyte telomere length (LTL) also entails an increased atherosclerotic risk. Methods: We studied 472 Whites and 190 African Americans (AfAs) enrolled in the Bogalusa Heart Study. Subjects were examined serially 3-13 times for HDL-C over an average period of 27.8 years from childhood through young adulthood. LTL was measured twice during adulthood at a mean age of 31.5 years (baseline exam) and 37.8 years (follow-up exam). HDL-C trajectories with age were constructed and the area under the curve (AUC) was used as a measure of cumulative HDL-C levels. Results: Multivariate regression analyses showed that LTL was positively associated with HDL-C …

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Elevated inflammation levels in depressed adults with a history of childhood maltreatment.

Context: The association between depression and inflammation is inconsistent across research samples. Objective: To test whether a history of childhood maltreatment could identify a subgroup of depressed individuals with elevated inflammation levels, thus helping to explain previous inconsistencies. Design: Prospective longitudinal cohort study. Setting: New Zealand. Participants: A representative birth cohort of 1000 individuals was followed up to age 32 years as part of the Dunedin Multidisciplinary Health and Development Study. Study members were assessed for history of childhood maltreatment and current depression. Main outcome measures: Inflammation was assessed using a clinically relevant categorical measure of high-sensitivity C-reactive protein (>3 mg/L) and a dimensional inflammation factor indexing the shared variance of continuous measures of high-sensitivity C-reactive protei…

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Leukocyte telomere length and cardiovascular disease in the cardiovascular health study.

The telomere length of replicating somatic cells is inversely correlated with age and has been reported to be associated cross-sectionally with cardiovascular disease (CVD). Leukocyte telomere length, as expressed by mean terminal restriction fragment (TRF) length, was measured in 419 randomly selected participants from the Cardiovascular Health Study, comprising a community-dwelling cohort recruited in four US communities. The authors investigated associations between TRF length and selected measures of subclinical CVD/risk factors for CVD (data were collected at the 1992/1993 clinic visit) and incident CVD (ascertained through June 2002). In these participants (average age = 74.2 years (standard deviation, 5.2)), mean TRF length was 6.3 kilobase pairs (standard deviation, 0.62). Significant or borderline inverse associations were found between TRF length and diabetes, glucose, insulin,…

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Burn size determines the inflammatory and hypermetabolic response.

Background: Increased burn size leads to increased mortality of burned patients. Whether mortality is due to inflammation, hypermetabolism or other pathophysiologic contributing factors is not entirely determined. The purpose of the present study was to determine in a large prospective clinical trial whether different burn sizes are associated with differences in inflammation, body composition, protein synthesis, or organ function. Methods: Pediatric burned patients were divided into four burn size groups: <40% total body surface area (TBSA) burn, 40-59% TBSA burn, 60-79% TBSA burn, and >80% TBSA burn. Demographic and clinical data, hypermetabolism, the inflammatory response, body composition, the muscle protein net balance, serum and urine hormones and proteins, and cardiac function and changes in liver size were determined. Results: One hundred and eighty-nine pediatric patients of sim…

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Evidence for low-grade systemic proinflammatory activity in patients with posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) may increase cardiovascular risk but the psychophysiological mechanisms involved are elusive. We hypothesized that proinflammatory activity is elevated in patients with PTSD as diagnosed by the Clinician Administered PTSD Scale (CAPS) interview. Plasma levels of proinflammatory C-reactive protein (CRP), interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha, and of anti-inflammatory IL-4 and IL-10 were measured in 14 otherwise healthy PTSD patients and in 14 age- and gender-matched healthy non-PTSD controls. Levels of TNF-alpha (p=0.038; effect size Cohen's d=0.58) and of IL-1beta (p=0.075, d=0.68) were higher in patients than in controls. CRP (d=0.10), IL-6 (d=0.18), IL-4 (d=0.42), and IL-10 (d=0.37) were not significantly different between groups. Controlling for traditional cardiovascular risk factors, mood, and time since trauma revea…

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Childhood maltreatment predicts adult inflammation in a life-course study.

Stress in early life has been associated with insufficient glucocorticoid signaling in adulthood, possibly affecting inflammation processes. Childhood maltreatment has been linked to increased risk of adult disease with potential inflammatory origin. However, the impact of early life stress on adult inflammation is not known in humans. We tested the life-course association between childhood maltreatment and adult inflammation in a birth cohort followed to age 32 years as part of the Dunedin Multidisciplinary Health and Development Study. Regression models were used to estimate the effect of maltreatment on inflammation, adjusting for co-occurring risk factors and potential mediating variables. Maltreated children showed a significant and graded increase in the risk for clinically relevant C-reactive protein levels 20 years later, in adulthood [risk ratio (RR)=1.80, 95% confidence interva…

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Associations between adolescent adversity and young adult depression symptoms and allostatic load in Mexican-origin individuals.

Childhood adversity increases risk for depression and higher allostatic load (AL), defined as long-term wear and tear on the body, and adolescence is an especially sensitive time for adversity to be biologically embedded. Individuals of Mexican origin may face multiple forms of adversities relating to their intersectional identities of ethnicity and class, including ethnic discrimination and economic hardship, the experience of which may further depend on sex. However, relatively little research has simultaneously assessed associations between these two types of adolescent adversity and outcomes of both young adult depression and AL longitudinally in Mexican-origin individuals. This preregistered study addressed these gaps in a longitudinal study of 208 Mexican-origin participants. Ethnic discrimination and economic hardship were assessed annually from ages 10-19 and AL and depression sy…

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The long-term effects of housing insecurity in young adulthood on subsequent material hardship, physiological and mental health.

Economic and material hardship, including housing insecurity - limited or uncertain availability or access to safe, quality, and affordable housing - is strongly linked to negative physical and mental health outcomes among adolescents and adults. However, data limitations and the inherent selectivity of housing insecurity have hindered comprehensive analysis of its long-term effects on physiological and mental health. This study uses data from The National Longitudinal Study of Adolescent to Adult Health (Add Health) to construct a sample of participants who experienced housing insecurity between the ages of 18-26 (Wave III) to a suitable control group using propensity score matching. We assess the effects of housing insecurity on (1) material hardship at Wave IV (ages 24-32), (2) allostatic load (AL) and depression symptoms at Waves IV and V (ages 33-43), and (3) the change in allostati…

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Cellular allostatic load is linked to increased energy expenditure and accelerated biological aging.

Stress triggers anticipatory physiological responses that promote survival, a phenomenon termed allostasis. However, the chronic activation of energy-dependent allostatic responses results in allostatic load, a dysregulated state that predicts functional decline, accelerates aging, and increases mortality in humans. The energetic cost and cellular basis for the damaging effects of allostatic load have not been defined. Here, by longitudinally profiling three unrelated primary human fibroblast lines across their lifespan, we find that chronic glucocorticoid exposure increases cellular energy expenditure by ∼60%, along with a metabolic shift from glycolysis to mitochondrial oxidative phosphorylation (OxPhos). This state of stress-induced hypermetabolism is linked to mtDNA instability, non-linearly affects age-related cytokines secretion, and accelerates cellular aging based on DNA methylat…

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Association of Allostatic Load With All-Cause Mortality in Patients With Breast Cancer.

Importance: Elevated allostatic load (AL) has been associated with adverse socioenvironmental stressors and tumor characteristics that convey poor prognosis in patients with breast cancer. Currently, the association between AL and all-cause mortality in patients with breast cancer is unknown. Objective: To examine the association between AL and all-cause mortality in patients with breast cancer. Design, setting, and participants: This cohort study used data from an institutional electronic medical record and cancer registry at the National Cancer Institute Comprehensive Cancer Center. Participants were patients with breast cancer diagnoses (stage I-III) between January 1, 2012, through December 31, 2020. Data were analyzed from April 2022 through November 2022. Exposure: AL was expressed as a summary score calculated by assigning 1 point for biomarkers in the worst sample quartile. High …

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Assimilation, Acculturation, and Allostatic Load in U.S.- and Foreign-Born Hispanics.

The present study assessed how the adaptation to American culture by United States (U.S.)-born and foreign-born Hispanics living in the U.S. may influence stress-related physiological aspects that may impair health. Data on 8,360 Hispanics living in the U.S. categorized as U.S.-born (n = 3347) and foreign-born (n = 5013) from NHANES 1999-2010 (ages 18-85) were used. Stress-related physiological impact was measured by the allostatic load index (ALoad). Adaptation to American culture was evaluated through three acculturation-related measures. The average age was 39.39 years in a sample where 51% were males. ALoad was classified as no load (15.41%), low load (55.33%), and high load (29.24%). The U.S.-born Hispanics showed higher ALoad compared to foreign-born Hispanics (p < 0.001). Among foreign-born Hispanics, length of residence (LOR) and age of arrival in the U.S. (AOA) were associated w…

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Prediagnostic Allostatic Load as a Predictor of Poorly Differentiated and Larger Sized Breast Cancers among Black Women in the Women's Circle of Health Follow-Up Study.

Background: Few studies have empirically tested the association of allostatic load (AL) with breast cancer clinicopathology. The aim of this study was to examine the association of AL, measured using relevant biomarkers recorded in medical records before breast cancer diagnosis, with unfavorable tumor clinicopathologic features among Black women. Methods: In a sample of 409 Black women with nonmetastatic breast cancer who are enrolled in the Women's Circle of Health Follow-Up Study, we estimated prediagnostic AL using two measures: AL measure 1 [lipid profile-based-assessed by systolic and diastolic blood pressure (SBP, DBP), high-density lipoprotein, low-density lipoprotein, total cholesterol, triglycerides, and glucose levels; waist circumference; and use of diabetes, hypertension, or hypercholesterolemia medication] and AL measure 2 (inflammatory index-based-assessed by SBP, DBP, gluc…

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Choroid Plexus Enlargement and Allostatic Load in Schizophrenia.

Although schizophrenia is a brain disorder, increasing evidence suggests that there may be body-wide involvement in this illness. However, direct evidence of brain structures involved in the presumed peripheral-central interaction in schizophrenia is still unclear. Seventy-nine previously treatment-naïve first-episode schizophrenia patients who were within 2-week antipsychotics initial stabilization, and 41 age- and sex-matched healthy controls were enrolled in the study. Group differences in subcortical brain regional structures measured by MRI and the subclinical cardiovascular, metabolic, immune, and neuroendocrine biomarkers as indexed by allostatic load, and their associations were explored. Compared with controls, patients with schizophrenia had significantly higher allostatic load (P = .001). Lateral ventricle (P < .001), choroid plexus (P < .001), and thalamus volumes (P < .001) …

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Pervasive Discrimination and Allostatic Load in African American and White Adults.

Objective: This study aimed to examine associations among race, the accumulation of multiple forms of discriminatory experiences (i.e., "pervasive discrimination"), and allostatic load (AL) in African Americans and whites in midlife. Methods: Using data collected in 2004 to 2006 from 226 African American and 978 white adults (57% female; mean [SD] age = 54.7 [0.11] years) in the Midlife in the United States II Biomarker Project, a pervasive discrimination score was created by combining three discrimination scales, and an AL score was created based on 24 biomarkers representing seven physiological systems. Linear regression models were conducted to examine the association between pervasive discrimination and AL, adjusting for demographics and medical, behavioral, and personality covariates. A race by pervasive discrimination interaction was also examined to determine whether associations …

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Social Allostasis and Social Allostatic Load: A New Model for Research in Social Dynamics, Stress, and Health.

Theories such as social baseline theory have argued that social groups serve a regulatory function but have not explored whether this regulatory process carries costs for the group. Allostatic load, the wear and tear on regulatory systems caused by chronic or frequent stress, is marked by diminished stress system flexibility and compromised recovery. We argue that allostatic load may develop within social groups as well and provide a model for how relationship dysfunction operates. Social allostatic load may be characterized by processes such as groups becoming locked into static patterns of interaction and may ultimately lead to up-regulation or down-regulation of a group's set point, or the optimal range of arousal or affect around which the group tends to converge. Many studies of emotional and physiological linkage within groups have reported that highly correlated states of arousal,…

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Direct and indirect associations of cognitive reappraisal and suppression with disease biomarkers.

Objective: Habitual use of emotion regulation strategies may influence physical health. We examined whether the tendencies to employ cognitive reappraisal and suppression were associated with health biomarkers, and whether stress and sleep quality mediated these associations. Design & main outcome measures: Using data from the Biomarkers substudy (n = 1255) of the national Midlife in the U.S. Study, we tested the hypothesis that there would be indirect, but not direct, associations of cognitive reappraisal and suppression to biomarker indicators of multisystem physiological dysregulation, that is, allostatic load (AL). We computed the proportion of biomarkers in the highest risk quartile within seven biological systems, and summed these scores to compute AL. Associations with the biological systems were also examined separately. Results: Neither reappraisal nor suppression was directly a…

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Allostatic Load: Importance, Markers, and Score Determination in Minority and Disparity Populations.

Allostatic load is a physiological measure of the cumulative burden of stress on the body assessed by markers of physiological dysregulation. It is a multisystem construct that quantifies biological risk which leads to poor health and maladaptive trajectories. In this overview, which is based on a presentation made at the Flip the Script: Understanding African American Women's Resilience in the Face of Allostatic Load meeting at Ohio State University in August 2018, we build upon previous reviews by discussing four key aspects of allostatic load, specifically its: (1) importance, (2) operationalization, (3) use in minority health and health disparities research, and (4) value in such research. Operationalized in various ways, allostatic load is composed of 10 original markers and additional markers deriving from research among minority and disparity populations. The markers represent fou…

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