Circadian rhythm and light

قَالَ مُوسَىٰٓ أَتَقُولُونَ لِلۡحَقِّ لَمَّا جَآءَكُمۡۖ أَسِحۡرٌ هَٰذَا وَلَا يُفۡلِحُ ٱلسَّٰحِرُونَ

Moses said, ‘Is this what you say about the Truth when it comes to you? Is this sorcery? Sorcerers never prosper.’

فَلَمَّا جَآءَ ٱلسَّحَرَةُ قَالَ لَهُم مُّوسَىٰٓ أَلۡقُواْ مَآ أَنتُم مُّلۡقُونَ

When the sorcerers came, Moses said to them, ‘Throw down whatever you have.’

فَلَمَّآ أَلۡقَوۡاْ قَالَ مُوسَىٰ مَا جِئۡتُم بِهِ ٱلسِّحۡرُۖ إِنَّ ٱللَّهَ سَيُبۡطِلُهُۥٓ إِنَّ ٱللَّهَ لَا يُصۡلِحُ عَمَلَ ٱلۡمُفۡسِدِينَ

When they did so, Moses said, ‘Everything you have brought is sorcery and God will show it to be false. God does not make the work of mischief-makers right

وَٱتَّبَعُواْ مَا تَتۡلُواْ ٱلشَّيَٰطِينُ عَلَىٰ مُلۡكِ سُلَيۡمَٰنَۖ وَمَا كَفَرَ سُلَيۡمَٰنُ وَلَٰكِنَّ ٱلشَّيَٰطِينَ كَفَرُواْ يُعَلِّمُونَ ٱلنَّاسَ ٱلسِّحۡرَ وَمَآ أُنزِلَ عَلَى ٱلۡمَلَكَيۡنِ بِبَابِلَ هَٰرُوتَ وَمَٰرُوتَۚ وَمَا يُعَلِّمَانِ مِنۡ أَحَدٍ حَتَّىٰ يَقُولَآ إِنَّمَا نَحۡنُ فِتۡنَةࣱ فَلَا تَكۡفُرۡۖ فَيَتَعَلَّمُونَ مِنۡهُمَا مَا يُفَرِّقُونَ بِهِۦ بَيۡنَ ٱلۡمَرۡءِ وَزَوۡجِهِۦۚ وَمَا هُم بِضَآرِّينَ بِهِۦ مِنۡ أَحَدٍ إِلَّا بِإِذۡنِ ٱللَّهِۚ وَيَتَعَلَّمُونَ مَا يَضُرُّهُمۡ وَلَا يَنفَعُهُمۡۚ وَلَقَدۡ عَلِمُواْ لَمَنِ ٱشۡتَرَىٰهُ مَا لَهُۥ فِي ٱلۡأٓخِرَةِ مِنۡ خَلَٰقࣲۚ وَلَبِئۡسَ مَا شَرَوۡاْ بِهِۦٓ أَنفُسَهُمۡۚ لَوۡ كَانُواْ يَعۡلَمُونَ

and followed what the evil ones had fabricated about the Kingdom of Solomon instead. Not that Solomon himself was a disbeliever; it was the evil ones who were disbelievers. They taught people witchcraft and what was revealed in Babylon to the two angels Harut and Marut. Yet these two never taught anyone without first warning him, ‘We are sent only to tempt- do not disbelieve.’ From these two, they learned what can cause discord between man and wife, although they harm no one with it except by God’s leave. They learned what harmed them, not what benefited them, knowing full well that whoever gained [this knowledge] would lose any share in the Hereafter. Evil indeed is the [price] for which they sold their souls, if only they knew

وَجَآءَ ٱلسَّحَرَةُ فِرۡعَوۡنَ قَالُوٓاْ إِنَّ لَنَا لَأَجۡرًا إِن كُنَّا نَحۡنُ ٱلۡغَٰلِبِينَ

The sorcerers came to Pharaoh and said, ‘Shall we be rewarded if we win?’

وَأُلۡقِيَ ٱلسَّحَرَةُ سَٰجِدِينَ

The sorcerers fell to their knees

(And follow that which the devils falsely related against the kingdom of Solomon�) [2:102]. Muhammad ibn 'Abd al-'Aziz al-Qantari informed us> Abu'l-Fadl al-Haddadi> Abu Yazid al-Khalidi> Ishaq ibn Ibrahim> Jarir> Husayn ibn 'Abd al-Rahman> 'Imran ibn al-Harith who said: �Once as we were sitting with Ibn 'Abbas when he said: 'The devils used to eavesdrop on heaven. One of them would bring a word of truth from therein, and when he is trusted for telling the truth, he would add to it seventy lies with which he earns the hearts of people. When Solomon came to know about it, he took it and buried it beneath his throne. When he died, a devil stood in the street and said: 'Shall I guide you to Solomon's guarded treasure, the like of which he does not have?' They said: 'Yes, do'. He said: 'It is under his throne; go and unearth it'. They said: 'This is magic'. Different nations then copied it f

And they follow wa’ttaba‘ū is a supplement to nabadha ‘it cast away’ what the devils used to relate during the time of Solomon’s kingdom in the way of sorcery it is said that they the devils buried these books of sorcery underneath his throne when his kingdom was taken from him; it is also said that they used to listen stealthily and add fabrications to what they heard and then pass it on to the priests who would compile it in books; this would be disseminated and rumours spread that the jinn had knowledge of the Unseen. Solomon gathered these books and buried them. When he died the devils showed people where these books were and the latter brought them out and found that they contained sorcery and said ‘Your kingdom was only thanks to what is in here’; they then took to learning them and rejected the Scriptures of their prophets. In order to demonstrate Solomon’s innocence and in repudi

And the sorcerers came to Pharaoh saying ‘Surely a-inna read pronouncing both hamzas or by not pronouncing the second one but inserting an alif between the two in both cases there will be a wage for us if we are the victors?’

And the sorcerers fell down in prostration.

And so the sorcerers came to Fir'awn. They said: "Indeed there will be a (good) reward for us if we are the victors. (113)He said: "Yes, and moreover you will (in that case) be of the nearest (to me). (114) The Magicians convene and change Their Ropes into Snakes before Musa Allah describes the conversation that took place between Fir'awn and the magicians he collected to defeat Musa, peace be upon him. Fir'awn told them that he will reward them and give them tremendous provisions. He made them hope in acquiring what they wished for and to make them among his private audience and best associates. When they were assured of the cursed Fir'awn's promises,

And We revealed to Musa (saying): "Throw your stick," and behold! It swallowed up straight away all the falsehood which they showed (117)Thus truth was confirmed, and all that they did was made of no effect (118)So they were defeated there and returned disgraced (119)And the sorcerers fell down prostrate (120)They said: "We believe in the Lord of all that exists (121)"The Lord of Musa and Harun. (122) Musa defeats the Magicians, Who believe in Him Allah states that at that tremendous moment, in which Allah differentiated between Truth and Falsehood, He sent a revelation to His servant and Messenger Musa, peace be upon him, ordering him to throw the stick that he held in his right hand, فَإِذَا هِيَ تَلْقَفُ (It swallowed straight away) and devoured, مَا يَأْفِكُونَ (all the falsehood which they showed.) the magic that they caused the illusion with, of magic with which they caused m

حَدَّثَنَا أَبُو نُعَيْمٍ، قَالَ حَدَّثَنَا سُفْيَانُ، عَنِ الأَسْوَدِ، قَالَ سَمِعْتُ جُنْدَبًا، يَقُولُ اشْتَكَى النَّبِيُّ صلى الله عليه وسلم فَلَمْ يَقُمْ لَيْلَةً أَوْ لَيْلَتَيْنِ‏.‏

Narrated Jundab:The Prophet (ﷺ) became sick and did not get up (for Tahajjud prayer) for a night or two

حَدَّثَنَا ابْنُ مُقَاتِلٍ، أَخْبَرَنَا عَبْدُ اللَّهِ، أَخْبَرَنَا مَعْمَرٌ، عَنِ الزُّهْرِيِّ، عَنْ هِنْدٍ بِنْتِ الْحَارِثِ، عَنْ أُمِّ سَلَمَةَ ـ رضى الله عنها ـ أَنَّ النَّبِيَّ صلى الله عليه وسلم اسْتَيْقَظَ لَيْلَةً فَقَالَ ‏ "‏ سُبْحَانَ اللَّهِ مَاذَا أُنْزِلَ اللَّيْلَةَ مِنَ الْفِتْنَةِ، مَاذَا أُنْزِلَ مِنَ الْخَزَائِنِ مَنْ يُوقِظُ صَوَاحِبَ الْحُجُرَاتِ، يَا رُبَّ كَاسِيَةٍ فِي الدُّنْيَا عَارِيَةٍ فِي الآخِرَةِ ‏"‏‏.‏

Narrated Um Salama:One night the Prophet (ﷺ) got up and said, "Subhan Allah! How many afflictions Allah has revealed tonight and how many treasures have been sent down (disclosed). Go and wake the sleeping lady occupants of these dwellings up (for prayers), perhaps a well dressed in this world may be naked in the Hereafter

حَدَّثَنَا عَبْدُ اللَّهِ بْنُ مَسْلَمَةَ، قَالَ قَرَأْتُ عَلَى مَالِكٍ عَنِ ابْنِ شِهَابٍ، أَنَّ عُمَرَ بْنَ عَبْدِ الْعَزِيزِ، أَخَّرَ الصَّلاَةَ يَوْمًا، فَدَخَلَ عَلَيْهِ عُرْوَةُ بْنُ الزُّبَيْرِ، فَأَخْبَرَهُ أَنَّ الْمُغِيرَةَ بْنَ شُعْبَةَ أَخَّرَ الصَّلاَةَ يَوْمًا وَهْوَ بِالْعِرَاقِ، فَدَخَلَ عَلَيْهِ أَبُو مَسْعُودٍ الأَنْصَارِيُّ فَقَالَ مَا هَذَا يَا مُغِيرَةُ أَلَيْسَ قَدْ عَلِمْتَ أَنَّ جِبْرِيلَ نَزَلَ فَصَلَّى، فَصَلَّى رَسُولُ اللَّهِ صلى الله عليه وسلم ثُمَّ صَلَّى فَصَلَّى رَسُولُ اللَّهِ صلى الله عليه وسلم ثُمَّ صَلَّى فَصَلَّى رَسُولُ اللَّهِ صلى الله عليه وسلم ثُمَّ صَلَّى فَصَلَّى رَسُولُ اللَّهِ صلى الله عليه وسلم ثُمَّ صَلَّى فَصَلَّى رَسُولُ اللَّهِ صلى الله عليه وسلم ثُمَّ قَالَ ‏ "‏ بِهَذَا أُمِرْتُ ‏"‏‏.‏ فَقَالَ عُمَرُ لِعُرْوَةَ اعْلَمْ مَا تُحَدِّثُ أَوَإِنَّ جِبْرِيلَ هُوَ أَقَامَ لِرَسُولِ اللَّهِ صلى الله عليه وسلم وَقْتَ الصَّلاَةِ‏.‏ قَالَ عُرْوَةُ كَذَلِكَ كَانَ بَشِيرُ بْنُ أَبِي مَسْعُودٍ يُحَدِّثُ عَنْ أَبِيهِ‏.‏ قَالَ عُرْوَةُ وَلَقَدْ حَدَّثَتْنِي عَائِشَةُ، أَنَّ رَسُولَ اللَّهِ صلى الله عليه وسلم كَانَ يُصَلِّي الْعَصْرَ، وَالشَّمْسُ فِي حُجْرَتِهَا قَبْلَ أَنْ تَظْهَرَ‏.‏

Narrated Ibn Shihab:Once `Umar bin `Abdul `Aziz delayed the prayer and `Urwa bin Az-Zubair went to him and said, "Once in 'Iraq, Al-Mughira bin Shu`ba delayed his prayers and Abi Mas`ud Al-Ansari went to him and said, 'O Mughira! What is this? Don't you know that once Gabriel came and offered the prayer (Fajr prayer) and Allah's Messenger (ﷺ) prayed too, then he prayed again (Zuhr prayer) and so did Allah's Apostle and again he prayed (`Asr prayers and Allah's Messenger (ﷺ) did the same; again he prayed (Maghrib-prayer) and so did Allah's Messenger (ﷺ) and again prayed (`Isha prayer) and so did Allah's Apostle and (Gabriel) said, 'I was ordered to do so (to demonstrate the prayers prescribed to you)?'" `Umar (bin `Abdul `Aziz) said to `Urwa, "Be sure of what you Say. Did Gabriel lead Allah's Messenger (ﷺ) at the stated times of the prayers?" `Urwa replied, "Bashir bin Abi Mas`ud narrated like this on the authority of his father." `Urwa added, "Aisha told me that Allah's Messenger (ﷺ) used to pray `Asr prayer when the sunshine was still inside her residence (during the early time of `Asr)

حَدَّثَنَا قُتَيْبَةُ بْنُ سَعِيدٍ، قَالَ حَدَّثَنَا عَبَّادٌ ـ هُوَ ابْنُ عَبَّادٍ ـ عَنْ أَبِي جَمْرَةَ، عَنِ ابْنِ عَبَّاسٍ، قَالَ قَدِمَ وَفْدُ عَبْدِ الْقَيْسِ عَلَى رَسُولِ اللَّهِ صلى الله عليه وسلم فَقَالُوا إِنَّا مِنْ هَذَا الْحَىِّ مِنْ رَبِيعَةَ، وَلَسْنَا نَصِلُ إِلَيْكَ إِلاَّ فِي الشَّهْرِ الْحَرَامِ، فَمُرْنَا بِشَىْءٍ نَأْخُذْهُ عَنْكَ، وَنَدْعُو إِلَيْهِ مَنْ وَرَاءَنَا‏.‏ فَقَالَ ‏ "‏ آمُرُكُمْ بِأَرْبَعٍ، وَأَنْهَاكُمْ عَنْ أَرْبَعٍ الإِيمَانِ بِاللَّهِ ـ ثُمَّ فَسَّرَهَا لَهُمْ شَهَادَةُ أَنْ لاَ إِلَهَ إِلاَّ اللَّهُ، وَأَنِّي رَسُولُ اللَّهِ، وَإِقَامُ الصَّلاَةِ، وَإِيتَاءُ الزَّكَاةِ، وَأَنْ تُؤَدُّوا إِلَىَّ خُمُسَ مَا غَنِمْتُمْ، وَأَنْهَى عَنِ الدُّبَّاءِ وَالْحَنْتَمِ وَالْمُقَيَّرِ وَالنَّقِيرِ ‏"‏‏.‏

Narrated Ibn `Abbas:"Once a delegation of `Abdul Qais came to Allah's Messenger (ﷺ) and said, "We belong to such and such branch of the tribe of Rabi'ah and we can only come to you in the sacred months. Order us to do something good so that we may take it from you and also invite to it those whom we have left behind (at home)." So he said, "I order you to do four things and forbid you from four things: To believe in Allah" - and then he explained it to them "to testify that none has the right to be worshipped but Allah and that I am Allah's Messenger (ﷺ), to establish the prayers (at the stated times), to pay the Zakat (obligatory charity), to hand me the Khumus (fifth) if you acquire spoils of war. And I forbid from (using) Dubba, Hantam, Muqaiyyar, and Naqir (all these were utensils used for the preparation of alcoholic drinks)

أَخْبَرَنَا قُتَيْبَةُ، قَالَ حَدَّثَنَا اللَّيْثُ بْنُ سَعْدٍ، عَنِ ابْنِ شِهَابٍ، أَنَّ عُمَرَ بْنَ عَبْدِ الْعَزِيزِ، أَخَّرَ الْعَصْرَ شَيْئًا فَقَالَ لَهُ عُرْوَةُ أَمَا إِنَّ جِبْرِيلَ عَلَيْهِ السَّلاَمُ قَدْ نَزَلَ فَصَلَّى أَمَامَ رَسُولِ اللَّهِ صلى الله عليه وسلم ‏.‏ فَقَالَ عُمَرُ اعْلَمْ مَا تَقُولُ يَا عُرْوَةُ ‏.‏ فَقَالَ سَمِعْتُ بَشِيرَ بْنَ أَبِي مَسْعُودٍ يَقُولُ سَمِعْتُ أَبَا مَسْعُودٍ يَقُولُ سَمِعْتُ رَسُولَ اللَّهِ صلى الله عليه وسلم يَقُولُ ‏ "‏ نَزَلَ جِبْرِيلُ فَأَمَّنِي فَصَلَّيْتُ مَعَهُ ثُمَّ صَلَّيْتُ مَعَهُ ثُمَّ صَلَّيْتُ مَعَهُ ثُمَّ صَلَّيْتُ مَعَهُ ثُمَّ صَلَّيْتُ مَعَهُ ‏"‏ ‏.‏ يَحْسُبُ بِأَصَابِعِهِ خَمْسَ صَلَوَاتٍ ‏.‏

It was narrated from Ibn Shihab that 'Umar bin 'Abdul-'Aziz delayed the 'Asr prayer a little. 'Urwah said to him:"Jibril came down and led the Messenger of Allah (ﷺ) in prayer." 'Umar said: "Watch what you are saying, O 'Urwah!" He said: "I heard Bashir bin Abi Mas'ud say: 'I heard Abu Mas'ud say: "I heard the Messenger of Allah (ﷺ) say: 'Jibril came down and led me in prayer, and I prayed with him, then I prayed with him, then I prayed with him, then I prayed with him, then I prayed with him - and he counted off five prayers on his fingers

أَخْبَرَنَا مُحَمَّدُ بْنُ عَبْدِ الأَعْلَى، قَالَ حَدَّثَنَا خَالِدٌ، قَالَ حَدَّثَنَا شُعْبَةُ، قَالَ حَدَّثَنَا سَيَّارُ بْنُ سَلاَمَةَ، قَالَ سَمِعْتُ أَبِي يَسْأَلُ أَبَا بَرْزَةَ، عَنْ صَلاَةِ، رَسُولِ اللَّهِ صلى الله عليه وسلم قُلْتُ أَنْتَ سَمِعْتَهُ قَالَ كَمَا أَسْمَعُكَ السَّاعَةَ فَقَالَ سَمِعْتُ أَبِي يَسْأَلُ عَنْ صَلاَةِ رَسُولِ اللَّهِ صلى الله عليه وسلم قَالَ كَانَ لاَ يُبَالِي بَعْضَ تَأْخِيرِهَا - يَعْنِي الْعِشَاءَ - إِلَى نِصْفِ اللَّيْلِ وَلاَ يُحِبُّ النَّوْمَ قَبْلَهَا وَلاَ الْحَدِيثَ بَعْدَهَا ‏.‏ قَالَ شُعْبَةُ ثُمَّ لَقِيتُهُ بَعْدُ فَسَأَلْتُهُ قَالَ كَانَ يُصَلِّي الظُّهْرَ حِينَ تَزُولُ الشَّمْسُ وَالْعَصْرَ يَذْهَبُ الرَّجُلُ إِلَى أَقْصَى الْمَدِينَةِ وَالشَّمْسُ حَيَّةٌ وَالْمَغْرِبَ لاَ أَدْرِي أَىَّ حِينٍ ذَكَرَ ثُمَّ لَقِيتُهُ بَعْدُ فَسَأَلْتُهُ فَقَالَ وَكَانَ يُصَلِّي الصُّبْحَ فَيَنْصَرِفُ الرَّجُلُ فَيَنْظُرُ إِلَى وَجْهِ جَلِيسِهِ الَّذِي يَعْرِفُهُ فَيَعْرِفُهُ ‏.‏ قَالَ وَكَانَ يَقْرَأُ فِيهَا بِالسِّتِّينَ إِلَى الْمِائَةِ ‏.‏

Shu'bah said:"Sayyar bin Salamah, narrated to us, he said: 'I heard my father ask Abu Barzah about the prayer of the Messenger of Allah (ﷺ).' I said: 'Did you really hear him?' He said: 'As I can hear you now.' He said: 'I heard my father ask about the prayer of the Messenger of Allah (ﷺ).' He said: 'He would not mind if he delayed it - meaning 'Isha' until midnight, and he did not like to sleep before it or speak after it.'" Shu'bah said: "Then I met him later on and asked him. He said: 'He used to pray Zauhr when the sun had passed its zenith, and (he would pray) 'Asr and a man could walk to the farthest point in Al-Madinah and the sun would still be clear and hot. And Maghrib, I do not know the time he mentioned.' After that I met him and asked him, and he said: 'He used to pray Fajr then after the prayer a man could regarding it, sitting next to him, look at the face of someone he knew and he could recognize it.' He said: 'And he used to recite in it between sixty and one hundred (verses)

وعبادته التي هو مشغول بها لا ينتقل إلى غيرها ولا يفتر عنها لا يستكبرون عن عبادته ولا يستحسرون يسبحون الليل والنهار لا يفترون ومفتاح مزيد الدرجات هي الصلوات

وينبغي أن لا ينفصل من طرف عرفة إلا بعد الغروب ليجمع في عرفة بين الليل والنهار وإن أمكنه الوقوف يوم الثامن ساعة عند إمكان الغلط في الهلال فهو الحزم وبه الأمن من الفوات

الباب الأول في فضيلة الأوراد وترتيبها في الليل والنهار

يشير إلى أنه غير متطلع إلى الأوقات بل هو مع الذي يقدر الليل والنهار

فهذا سؤال جاهل ظالم ضال مفرط في الجهل والظلم والضلال لأن خلق الأضداد والمتقابلات هو من كمال الربوبية كالليل والنهار والحر والبرد واللذة والألم والخير والشر والنعيم والجحيم

خلفة لمن أراد أن يذكر أو أراد شكورا} [الفرقان: 62]، أي يخلف أحدهما الآخر ليتدارك في أحدهما ما فات في الآخر. ### $ 2 - بيان عدد أوراد الليل والنهار وترتيبها

Diagnosis of circadian rhythm sleep disorders.: Insomnia and excessive sleepiness are common in the investigation of sleep-disordered breathing. Circadian rhythm sleep disorders are perhaps the most often overlooked conditions in the differential diagnosis of these symptoms. Circadian rhythm sleep disorders manifest as misalignment between the sleep period and the physical/social 24-h environmental cycle. The two most prevalent circadian rhythm sleep disorders are delayed sleep phase (common in adolescents) and advanced sleep phase (common in

Intrinsic circadian period of sighted patients with circadian rhythm sleep disorder, free-running type.: Background: Circadian rhythm sleep disorder, free-running type (FRT), is an intractable sleep disorder in which sleep and wake times progressively delay each day even in normal living environments. This disorder severely affects the social functioning of patients because of periodic nighttime insomnia, excessive daytime sleepiness, and a high rate of comorbid psychiatric disorders. Although abnormal regulation of the biological clock is suspected, the pathophysiology of FRT has yet to be elucida

Identification of a Preliminary Plasma Metabolome-based Biomarker for Circadian Phase in Humans.: Measuring individual circadian phase is important to diagnose and treat circadian rhythm sleep-wake disorders and circadian misalignment, inform chronotherapy, and advance circadian science. Initial findings using blood transcriptomics to predict the circadian phase marker dim-light melatonin onset (DLMO) show promise. Alternatively, there are limited attempts using metabolomics to predict DLMO and no known omics-based biomarkers predict dim-light melatonin offset (DLMOff). We analyzed the human

Home dim light melatonin onsets with measures of compliance in delayed sleep phase disorder.: The dim light melatonin onset (DLMO) assists with the diagnosis and treatment of circadian rhythm sleep disorders. Home DLMOs are attractive for cost savings and convenience, but can be confounded by home lighting and sample timing errors. We developed a home saliva collection kit with objective measures of light exposure and sample timing. We report on our first test of the kit in a clinical population. Thirty-two participants with delayed sleep phase disorder (DSPD; 17 women, aged 18-52 years)

A randomized controlled trial with bright light and melatonin for the treatment of delayed sleep phase disorder: effects on subjective and objective sleepiness and cognitive function.: Delayed sleep phase disorder (DSPD) is a circadian rhythm sleep disorder. Patients with DSPD have problems initiating sleep if they go to bed at a conventional time, and they often have problems waking at desired times. If they rise early in the morning, they usually experience severe sleepiness during morning hours. In the present study, we investigated the short- and long-term effects on measures of subjective and objective sleepiness and cognitive function of bright light and melatonin treatm

Light-induced changes of the circadian clock of humans: increasing duration is more effective than increasing light intensity.: Study objectives: To evaluate the effect of increasing the intensity and/or duration of exposure on light-induced changes in the timing of the circadian clock of humans. Design: Multifactorial randomized controlled trial, between and within subject design Setting: General Clinical Research Center (GCRC) of an academic medical center Participants: 56 healthy young subjects (20-40 years of age) Interventions: Research subjects were admitted for 2 independent stays of 4 nights/3 days for treatment

Pharmacotherpy and Alzheimer's Disease: The M-Drugs (Melatonin, Minocycline, Modafinil, and Memantine) Approach.

Despite advances in understanding the pathophysiology of Alzheimer's disease (AD), its therapy remains largely symptomatic and supportive. Acetylcholinesterase inhibitors - the first-line drugs used today do not prevent and treat AD. So far, over 90 Phase 3 trials of AD have been unsuccessful with 99.0% failure rate. There is, therefore, an urgent need to find effective new therapies for AD. Owing to the multifactorial nature of AD pathogenesis, polypharmacy with drugs that target heterogeneous pathophysiological pathways, needs to be considered. Fortunately, several drugs used currently in clinical use as monotherapies can be exploited in AD. This article, therefore, presents a novel pharmacological treatment paradigm and recommends the use of valuable diseasemodifying approved drugs, viz. melatonin, minocycline, modafinil, and memantine (the "M" Drugs). Melatonin - a neuroprotector is …

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Melatonin in Alzheimer's disease.

Alzheimer's disease (AD), an age-related neurodegenerative disorder with progressive cognition deficit, is characterized by extracellular senile plaques (SP) of aggregated β-amyloid (Aβ) and intracellular neurofibrillary tangles, mainly containing the hyperphosphorylated microtubule-associated protein tau. Multiple factors contribute to the etiology of AD in terms of initiation and progression. Melatonin is an endogenously produced hormone in the brain and decreases during aging and in patients with AD. Data from clinical trials indicate that melatonin supplementation improves sleep, ameliorates sundowning and slows down the progression of cognitive impairment in AD patients. Melatonin efficiently protects neuronal cells from Aβ-mediated toxicity via antioxidant and anti-amyloid properties. It not only inhibits Aβ generation, but also arrests the formation of amyloid fibrils by a structu…

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The emerging role of melatonin agonists in the treatment of major depression: focus on agomelatine.

Major Depressive Disorder (MDD) is an extremely disabling, chronic and recurrent disease. Moreover, subthreshold depressive symptoms often persist during periods of apparent remission. Such symptoms include sleep disturbances, sexual dysfunction, weight gain, fatigue, disinterest, anxiety, and/or emotional blunting, which do not often respond to available antidepressant treatments. Agomelatine is a melatonergic agonist (at both MT1 and MT2 receptors) and serotonin 2C (5-HT2C) receptor antagonist. Agomelatine should be particularly useful in the treatment of MDD because of its unique pharmacological profile, accounting for its effective antidepressant action with a relative lack of serious adverse effects. Several clinical trials confirmed the antidepressant efficacy of agomelatine in patients with MDD, with significant efficacy even in severe manifestations of disease and on residual sub…

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Beneficial Effects of Early Time-Restricted Feeding on Metabolic Diseases: Importance of Aligning Food Habits with the Circadian Clock.

The importance of metabolic health is a major societal concern due to the increasing prevalence of metabolic diseases such as obesity, diabetes, and various cardiovascular diseases. The circadian clock is clearly implicated in the development of these metabolic diseases. Indeed, it regulates physiological processes by hormone modulation, thus helping the body to perform them at the ideal time of day. Since the industrial revolution, the actions and rhythms of everyday life have been modified and are characterized by changes in sleep pattern, work schedules, and eating habits. These modifications have in turn lead to night shift, social jetlag, late-night eating, and meal skipping, a group of customs that causes circadian rhythm disruption and leads to an increase in metabolic risks. Intermittent fasting, especially the time-restricted eating, proposes a solution: restraining the feeding …

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Bedtime procrastination and chronotype differentially predict adolescent sleep on school nights and non-school nights.

Objectives: Bedtime procrastination (BTP) refers to the tendency to delay sleep beyond an intended bedtime, in favor of continuing evening activities. BTP has been associated with negative sleep outcomes (later timing, shorter duration, poorer quality), and is viewed as a problem of exercising self-control. BTP could be particularly challenging in adolescents, given the combined effects of increasing bedtime autonomy, later chronotype, and a still developing self-control capacity. Thus far, research on BTP has only been based on self-report measures. Here we examined the influence of BTP on adolescent sleep, using objective measures of sleep. Methods: About 121 adolescents aged 14-19 years completed a survey on BTP, sleep quality, chronotype, and mental health. Subsequently, habitual sleep was actigraphically monitored for up to 2 weeks, and participants completed a temporal discounting …

matched on Circadian Rhythm (mesh), chronotype (text), Actigraphy (mesh), Actigraphy (keyword)

Melatonin Use in Pediatrics: A Clinical Review on Indications, Multisystem Effects, and Toxicity.

Exogenous melatonin is typically used for sleep regulation in the context of insomnia either in healthy children or those with neurodevelopmental disabilities. It is also used for the management of circadian rhythm sleep disorders in pediatric and adolescent patients. There are also many other possible indications that we will discuss in this paper beyond the role of melatonin for sleep regulation, including its potential use for various areas of medicine such as inflammatory conditions. Since melatonin is unregulated in the United States, distributed over the counter and perceived to be natural and safe, it has become available in many forms in the last two decades. With increasing sleep disturbances and mental health problems after the COVID-19 pandemic, melatonin has become even more popular and studies have shown a dramatic increase in use as well as resulting side effects, including…

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Melatonin and melatonergic drugs in sleep disorders.

Melatonin is an endogenous chronobiological regulator secreted mainly from the pineal gland, which has been used as a dietary supplement in the treatment of sleep problems, including insomnia, parasomnia, and circadian rhythm sleep disorders. However, the short half-life and rapid metabolism of melatonin limit its suitability as a drug. There are many melatonergic drugs used in the treatment of sleep disorders and several drugs are under investigation for approval. Ramelteon was the first melatonergic agonist approved as hypnotic agent by U.S. Food and Drug Administration for the treatment of insomnia. It exhibits higher selective affinity for melatonin 1a (MT1) receptor than melatonin 1b (MT2) receptor. This selectivity suggests that it targets sleep onset with no significant adverse effect or dependency. Agomelatin, naphtahalenic compound, act as a potent MT1/MT2 melatonergic receptor …

matched on Melatonin (keyword), circadian (text)

Empowering Melatonin Therapeutics with Drosophila Models.

Melatonin functions as a central regulator of cell and organismal function as well as a neurohormone involved in several processes, e.g., the regulation of the circadian rhythm, sleep, aging, oxidative response, and more. As such, it holds immense pharmacological potential. Receptor-mediated melatonin function mainly occurs through MT1 and MT2, conserved amongst mammals. Other melatonin-binding proteins exist. Non-receptor-mediated activities involve regulating the mitochondrial function and antioxidant cascade, which are frequently affected by normal aging as well as disease. Several pathologies display diseased or dysfunctional mitochondria, suggesting melatonin may be used therapeutically. Drosophila models have extensively been employed to study disease pathogenesis and discover new drugs. Here, we review the multiple functions of melatonin through the lens of functional conservation…

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Efficacy and safety of supplemental melatonin for delayed sleep-wake phase disorder in children: an overview.

Delayed sleep-wake phase disorder (DSPD) is the most frequently occurring intrinsic circadian rhythm sleep-wake disorder, with the highest prevalence in adolescence. Melatonin is the first-choice drug treatment. However, to date melatonin (in a controlled-release formulation) is only authorised for the treatment of insomnia in children with autism or Smiths-Magenis syndrome. Concerns have been raised with respect to the safety and efficacy of melatonin for more general use in children, as melatonin has not undergone the formal safety testing required for a new drug, especially long-term safety in children. Melatonin is known to have profound effects on the reproductive systems of rodents, sheep and primates, as well as effects on the cardiovascular, immune and metabolic systems. The objective of the present article was therefore to establish the efficacy and safety of exogenous melatonin…

matched on Melatonin (keyword), circadian (text)

Sleep Abnormalities in Multiple Sclerosis.

Purpose of review: This review summarizes the most well-documented sleep disorders seen in patients with multiple sclerosis (MS), with a special focus on the impact on quality of life. Recent findings: Sleep abnormalities in patients with MS are a multifactorial and relatively complex issue affecting approximately 60% of the patients while the pathophysiology of these symptoms is not fully understood. Circadian rhythm disorders and increased levels of pro-inflammatory cytokines have been recognized as potential players in affecting sleep homeostasis in MS patients. Medication-related side effects such as in immunotherapy and other factors such as lesion load can contribute to the disruption of normal sleep patterns. Most frequently encountered sleep disorders are insomnia, sleep-related movement disorders, sleep-related breathing disorders, and circadian rhythm disorders affecting both a…

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Voluntary wheel running exercise improves sleep disorder, circadian rhythm disturbance, and neuropathology in an animal model of Alzheimer's disease.

Introduction: The sleep-wake cycle and circadian rhythm disturbances are common in Alzheimer's disease (AD). However, it is not known if exercise has any benefit for the sleep disorders in AD. Methods: We conducted a 2-month voluntary wheel running (VWR) exercise (Ex) in an animal model of AD (APPSWE/PS1dE9 mice). We assessed behavioral circadian rhythm, sleep structure, circadian clock genes, cognitive function, and neurodegeneration in the suprachiasmatic nucleus (SCN), the hippocampus, and the cortex. Results: After VWR exercise in the AD mice, the rapid eye movement sleep was increased by 89%. The levels of circadian clock genes were significantly changed (brain and muscle arnt-like protein 1 [BMAL1] and retinoic acid receptor-related orphan receptorsα [RORα] reduced by 45.7% and 36.4%, reverse erythroblastosis virusα (REV-ERBα) increased by 119%) in the SCN by immunofluorescence sta…

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Chinese formula Guben-Jiannao Ye alleviates the dysfunction of circadian and sleep rhythms in APP/PS1 mice implicated in activation of the PI3K/AKT/mTOR signaling pathway.

Ethnopharmacological relevance: The Chinese formula Guben-Jiannao Ye (GBJNY) formula has a long history of usage in traditional Chinese medicine (TCM) for the treatment of learning and memory disorders as well as senile insomnia. This formulation is derived from Sun Simiao's five tonic pills. Furthermore, modern pharmacological investigations have revealed its ability to improve cognitive impairment and ameliorate sleep-wake circadian rhythm disorders. However, the precise mechanism underlying its efficacy remains elusive. Aim of the study: The current research explored the modulatory effects and possible mechanisms of GBJNY in circadian rhythm sleep-wake disorders and cognitive dysfunction in Alzheimer's disease using transcriptome sequencing and experimental validation. Materials and methods: The LC-MS/MS tandem technology was utilized to qualitatively discern the active components pre…

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Effect of antidepressants on circadian rhythms in fish: Insights and implications regarding the design of behavioural toxicity tests.

Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) are widely prescribed for the treatment of depression and anxiety disorders. Consequently, these compounds are frequently identified in global waterways where they may pose a hazard to aquatic biota. Evidence demonstrates these compounds to be capable of influencing the behaviour of fish, but the relevance of many reported behavioural endpoints is unclear and the value of some findings has been questioned. Since these compounds act on neuroendocrine-mediated pathways in vertebrates, the present study explored how exposure to two representative SSRIs (fluoxetine and sertraline) and an SNRI (venlafaxine) affect circadian rhythms in fish. Male mosquitofish (Gambusia holbrooki) were exposed to 1, 10 and 100μg/L concentrations of these compounds individually and when present as a full …

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The roles of dopamine and serotonin, and of their receptors, in regulating sleep and waking.

Based on electrophysiological, neurochemical and neuropharmacological approaches, it is currently accepted that serotonin (5-HT) and dopamine (DA) function to promote waking (W) and to inhibit slow wave sleep (SWS) and/or rapid-eye-movement sleep (REMS). Serotonergic neurons of the dorsal raphe nucleus (DRN) fire at a steady rate during W, decrease their firing during SWS and virtually cease activity during REMS. On the other hand, DA cells in the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNc) do not change their mean firing rate across the sleep-wake cycle. It has been proposed that DA cells in the midbrain show a change in temporal pattern rather than firing rate during the sleep-wake cycle. Available evidence tends to indicate that during W and REMS an increase of burst firing activity of DA neurons occurs together with an enhanced release of DA in the VTA, …

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The visual scoring of sleep and arousal in infants and children.

Age is probably the single most crucial factor determining how humans sleep. Age and level of vigilance significantly influence the electroencephalogram (EEG) and the polysomnogram (PSG). The Pediatric Task Force provide an evidence-based review of the age-related development of the polysomnographic features of sleep in neonates, infants, and children, assessing the reliability and validity of these features, and assessing alternative methods of measurement. We used this annotated supporting text to develop rules for scoring sleep and arousals in infants and children. A pediatric EEG or PSG can only be determined to be normal by assessing whether the EEG patterns are appropriate for maturational age. Sleep in infants at term can be scored as NREM and REM sleep because all the polysomnographic and EEG features of REM sleep are present and quiet sleep, if not NREM sleep, is at least "not R…

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Digital Engagement and Sleep Dysregulation in Young Adults: A Narrative Review.

Digital technology is embedded in daily life, and growing evidence suggests that evening and bedtime screen engagement may disrupt sleep in young adults. Associations appear stronger for bedtime exposure and problematic or addiction-like patterns of use than for total screen time alone. This review aims to synthesize current evidence on the relationship between smartphone and social media use and sleep outcomes in young adults, with particular attention to the timing of device use, problematic digital engagement, and psychological or behavioral factors that may influence sleep. A narrative literature review was conducted using a broad, non-systematic search of PubMed, Scopus, Web of Science, and Google Scholar. Observational, longitudinal, experimental, or interventional studies and higher-level syntheses were included when they contributed to conceptual understanding of the screen-sleep…

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Behavioural and transgenerational effects of artificial light at night (ALAN) of varying spectral compositions in zebrafish (Danio rerio).

Artificial light at night (ALAN) can disrupt the natural behaviour, physiology, and circadian rhythms of organisms exposed to it, and therefore presents a significant and widespread ecological concern. ALAN typically comprises a wide range of wavelengths, and different wavelengths have different effects on circadian clocks. In the animals investigated thus far, short and middle wavelengths are intensely involved in synchronisation and entrainment, but we still have a poor understanding of how different wavelengths might affect behaviour when animals are exposed to ALAN, in particular whether some wavelengths are disproportionally detrimental. This experiment examined the direct and transgenerational effects of 10 different wavelength treatments of ALAN on behaviour in zebrafish (Danio rerio), a diurnally active model organism. Across a 10-day period, female zebrafish were exposed to eith…

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Nyctinastic thallus movement in the liverwort Marchantia polymorpha is regulated by a circadian clock.

The circadian clock coordinates an organism's growth, development and physiology with environmental factors. One illuminating example is the rhythmic growth of hypocotyls and cotyledons in Arabidopsis thaliana. Such daily oscillations in leaf position are often referred to as sleep movements or nyctinasty. Here, we report that plantlets of the liverwort Marchantia polymorpha show analogous rhythmic movements of thallus lobes, and that the circadian clock controls this rhythm, with auxin a likely output pathway affecting these movements. The mechanisms of this circadian clock are partly conserved as compared to angiosperms, with homologs to the core clock genes PRR, RVE and TOC1 forming a core transcriptional feedback loop also in M. polymorpha.

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Analysis of circadian properties and healthy levels of blue light from smartphones at night.

This study proposes representative figures of merit for circadian and vision performance for healthy and efficient use of smartphone displays. The recently developed figures of merit for circadian luminous efficacy of radiation (CER) and circadian illuminance (CIL) related to human health and circadian rhythm were measured to compare three kinds of commercial smartphone displays. The CIL values for social network service (SNS) messenger screens from all three displays were higher than 41.3 biolux (blx) in a dark room at night, and the highest CIL value reached 50.9 blx. These CIL values corresponded to melatonin suppression values (MSVs) of 7.3% and 11.4%, respectively. Moreover, smartphone use in a bright room at night had much higher CIL and MSV values (58.7 ~ 105.2 blx and 15.4 ~ 36.1%, respectively). This study also analyzed the nonvisual and visual optical properties of the three sm…

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The personality profile of young adults with delayed sleep phase disorder.

Delayed sleep phase disorder (DSPD) is a circadian rhythm sleep disorder characterized by a substantial delay in the major sleep period, resulting in difficulties falling asleep and awakening at a socially desirable time in the morning. This study is the first to investigate the NEO-Personality Inventory-Revised profile of young adults with DSPD. The study includes 40 patients diagnosed with DSPD (mean age = 20.7) and 21 healthy controls (mean age = 21.1). Results showed that young adults with DSPD scored higher on Neuroticism, lower on Extroversion, and much lower on Conscientiousness than the control group. Assessing the personality profile of young adults with DSPD before initiating treatment might provide useful clinical guidance regarding the individual needs for follow up during treatment.

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Sleep disturbance and melatonin levels following traumatic brain injury.

Objectives: Sleep disturbances commonly follow traumatic brain injury (TBI) and contribute to ongoing disability. However, there are no conclusive findings regarding specific changes to sleep quality and sleep architecture measured using polysomnography. Possible causes of the sleep disturbances include disruption of circadian regulation of sleep-wakefulness, psychological distress, and a neuronal response to injury. We investigated sleep-wake disturbances and their underlying mechanisms in a TBI patient sample. Methods: This was an observational study comparing 23 patients with TBI (429.7 +/- 287.6 days post injury) and 23 age- and gender-matched healthy volunteers on polysomnographic sleep measures, salivary dim light melatonin onset (DLMO) time, and self-reported sleep quality, anxiety, and depression. Results: Patients with TBI reported higher anxiety and depressive symptoms and slee…

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Rapid changes in the light/dark cycle disrupt memory of conditioned fear in mice.

Background: Circadian rhythms govern many aspects of physiology and behavior including cognitive processes. Components of neural circuits involved in learning and memory, e.g., the amygdala and the hippocampus, exhibit circadian rhythms in gene expression and signaling pathways. The functional significance of these rhythms is still not understood. In the present study, we sought to determine the impact of transiently disrupting the circadian system by shifting the light/dark (LD) cycle. Such "jet lag" treatments alter daily rhythms of gene expression that underlie circadian oscillations as well as disrupt the synchrony between the multiple oscillators found within the body. Methodology/principal findings: We subjected adult male C57Bl/6 mice to a contextual fear conditioning protocol either before or after acute phase shifts of the LD cycle. As part of this study, we examined the impact …

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Common Sleep Disorders Affecting Older Adults.

Sleep disorders in older adults increase with aging, likely due to increased sleep latency, decreased sleep efficiency, and total sleep time. Common sleep issues include chronic insomnia, circadian rhythm sleep-wake disorders, sleep-related movement disorders, and sleep-disordered breathing. Diagnostic tools, such as a comprehensive sleep history and questionnaires, or a sleep log for more specific complaints, are commonly used. Polysomnography is not recommended as a routine test; however, it can be used for abnormal behaviors during sleep or if treatment fails. Sleep disorder management is based on the etiology and may include nonpharmacological and pharmacological alternative treatments. For example, nonpharmacological management for chronic insomnia and some sleep disorders may consist of cognitive behavioral therapy, sleep hygiene education, relaxation therapy, sleep restriction, li…

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Excessive Daytime Sleepiness: A Clinical Review.

Excessive daytime sleepiness (EDS) is a highly prevalent condition that is associated with significant morbidity. The causes of EDS are varied, and include inadequate sleep, sleep disordered breathing, circadian rhythm sleep-wake disorders, and central disorders of hypersomnolence (narcolepsy, idiopathic hypersomnia, and Kleine-Levin syndrome). Additionally, EDS could represent a symptom of an underlying medical or psychiatric disorder. Assessment of EDS includes a thorough sleep, medical, and psychiatric history, targeted clinical examination, and appropriate use of actigraphy to measure sleep duration and sleep-wake patterns, polysomnography to assess for associated conditions such as sleep-related breathing disorders or other factors that might disrupt nighttime sleep, multiple sleep latency testing to ascertain objective sleepiness and diagnose central disorders of hypersomnolence, a…

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Improving fatigue risk management in healthcare: A scoping review of sleep-related/ fatigue-management interventions for nurses and midwives (reprint).

Background: Nurses and midwives make up almost 50% of the global healthcare shift working workforce. Shift work interferes with sleep and causes fatigue with adverse effects for nurses' and midwives' health, as well as on patient safety and care. Where other safety-critical sectors have developed Fatigue Risk Management Systems, healthcare is behind the curve; with published literature only focussing on the evaluation of discreet sleep-related/fatigue-management interventions. Little is known, however, about which interventions have been evaluated for nurses and midwives. Our review is a critical first step to building the evidence-base for healthcare organisations seeking to address this important operational issue. Objectives: We address two questions: (1) what sleep-related/fatigue-management interventions have been assessed in nurses and midwives and what is their evidence-base? and …

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