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

Treatment of Circadian Rhythm Sleep-Wake Disorders.

Circadian rhythm sleep-wake disorders (CRSWDs) are a distinct class of sleep disorders caused by alterations to the circadian time-keeping system, its entrainment mechanisms, or a mismatch between the endogenous circadian rhythm and the external environment. The main clinical manifestations are insomnia and excessive daytime sleepiness that often lead to clinically meaningful distress or cause mental, physical, social, occupational, educational, or other functional impairment. CRSWDs are easily mistaken for insomnia or early waking up, resulting in inappropriate treatment. CRSWDs can be roughly divided into two categories, namely, intrinsic CRSWDs, in which sleep disturbances are caused by alterations to the endogenous circadian rhythm system due to chronic changes in the regulation or capture mechanism of the biological clock, and extrinsic circadian rhythm sleep-wake disorders, in whic…

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Why the dim light melatonin onset (DLMO) should be measured before treatment of patients with circadian rhythm sleep disorders.

Treatment of circadian rhythm sleep disorders (CRSD) may include light therapy, chronotherapy and melatonin. Exogenous melatonin is increasingly being used in patients with insomnia or CRSD. Although pharmacopoeias and the European food safety authority (EFSA) recommend administering melatonin 1-2 h before desired bedtime, several studies have shown that melatonin is not always effective if administered according to that recommendation. Crucial for optimal treatment of CRSD, melatonin and other treatments should be administered at a time related to individual circadian timing (typically assessed using the dim light melatonin onset (DLMO)). If not administered according to the individual patient's circadian timing, melatonin and other treatments may not only be ineffective, they may even result in contrary effects. Endogenous melatonin levels can be measured reliably in saliva collected a…

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Light, dark, and melatonin: emerging evidence for the importance of melatonin in ocular physiology.

Melatonin is a hormone, which is mainly produced by the pineal gland, a vestigial eye. Rather than the rods and cones, it is a newly discovered subgroup of photosensitive retinal ganglion cells, which is responsible for mediating the light-dark cycles, thus regulating melatonin's secretion. One of the correlates of the circadian rhythm of melatonin release is the habitual sleep pattern. Patients with circadian rhythm sleep disorders, including some blind patients with no light-induced suppression of melatonin, benefit from melatonin treatment. Melatonin is synthesized in the retina, lens, ciliary body as well as other parts of the body. In this review, we discuss the physiological roles of melatonin in the eye, as well as the potential therapeutic avenues currently under study.

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Light therapy with boxes or glasses to counteract effects of acute sleep deprivation.

Sleep deprivation, in the context of shift work, is an increasing major public health issue. We aimed to determine whether early light administration can counteract sleep deprivation effects, and to compare LED-glasses with a traditional light therapy box. This cross-over design study included 18 individuals exposed to light therapy for 30 minutes at 5 am after one night of complete sleep deprivation, to mimic the night shift condition. Individuals were randomly exposed to 10,000 Lux light box, 2,000 Lux LED blue-enriched glasses, and control (ambient dim-light at 8 lux). Alertness, cognition and mood were assessed throughout the night and following morning. Five women and 13 men (mean 24.78 year old) presented with a progressive and increasing alteration of alertness, cognition, and mood during each sleep deprivation. A rebound was observed at 8 am resulting from the circadian drive ove…

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Insights into behavioral vulnerability to differential sleep pressure and circadian phase from a functional ADA polymorphism.

Sleep loss affects human behavior in a nonuniform manner, depending on the cognitive domain and also the circadian phase. Besides, evidence exists about stable interindividual variations in sleep loss-related performance impairments. Despite this evidence, only a few studies have considered both circadian phase and neurobehavioral domain when investigating trait-like vulnerability to sleep manipulation. By applying a randomized, crossover design with 2 sleep pressure conditions (40 h sleep deprivation vs. 40 h multiple naps), we investigated the influence of a human adenosine deaminase (ADA) polymorphism (rs73598374) on several behavioral measures throughout nearly 2 circadian cycles. Confirming earlier studies, we observed that under sleep deprivation the previously reported vulnerable G/A-allele carriers felt overall sleepier than G/G-allele carriers. As expected, this difference was n…

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Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: two randomised controlled multicentre trials.

Background: Circadian rhythm sleep disorders are common causes of insomnia for millions of individuals. We did a phase II study to establish efficacy and physiological mechanism, and a phase III study to confirm efficacy of the melatonin agonist tasimelteon (VEC-162) for treatment of transient insomnia associated with shifted sleep and wake time. Methods: We undertook phase II and phase III randomised, double-blind, placebo-controlled, parallel-group studies. In a phase II study, 39 healthy individuals from two US sites were randomly assigned to tasimelteon (10 [n=9], 20 [n=8], 50 [n=7], or 100 mg [n=7]) or placebo (n=8). We monitored individuals for 7 nights: 3 at baseline, 3 after a 5-h advance of sleep-wake schedule with treatment before sleep, and 1 after treatment; we measured plasma melatonin concentration for circadian phase assessment. In a phase III study, 411 healthy individual…

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Circadian phase-shifting effects of repeated ramelteon administration in healthy adults.

Study objectives: To assess the ability of repeated daily oral ramelteon to facilitate re-entrainment of human circadian rhythms after an imposed phase advance of the sleep-wake cycle. Methods: A total of 75 healthy adult volunteers aged 18-45 years remained in a sleep laboratory for 6 days and 5 nights; a 5-h phase advance in their sleep-wake cycle was imposed under dim-light conditions. Oral ramelteon (1,2, 4, or 8 mg once daily for 4 days) or placebo was administered 30 min before bedtime. The primary endpoint was the phase of the circadian rhythm as assessed by the time at which salivary melatonin concentrations declined below 3 pg/mL after morning awakening (dim-light melatonin offset [DLMoff]). Results: After 4 days of once-daily treatment, participants receiving 1, 2, or 4 mg ramelteon exhibited statistically significant phase shifts in DLMoff of -88.0 (16.6), -80.5 (14.8), and -9…

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Light therapies to improve sleep in intrinsic circadian rhythm sleep disorders and neuro-psychiatric illness: A systematic review and meta-analysis.

Circadian dysregulation causes sleep disturbance and impacts quality of life and functioning. Some interventions target circadian entrainment through modifying light exposure, but existing reviews of light interventions for sleep improvement include few studies in psychiatric populations. We examined effect of light interventions on sleep quality, duration and timing, and effect moderators. We included controlled studies in intrinsic circadian rhythm disorders (such as advanced or delayed sleep) and in neuropsychiatric disorders with assumed high prevalence of circadian dysregulation (such as affective and psychotic disorders). Articles were identified through database searching: 40 studies reporting 49 relevant intervention comparisons met inclusion criteria. Meta-analysis showed improvements in sleep continuity (ES = -0.23, p = 0.000), self-reported sleep disturbance (ES = -0.32, p = 0…

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Disturbance of the Circadian System in Shift Work and Its Health Impact.

The various non-standard schedules required of shift workers force abrupt changes in the timing of sleep and light-dark exposure. These changes result in disturbances of the endogenous circadian system and its misalignment with the environment. Simulated night-shift experiments and field-based studies with shift workers both indicate that the circadian system is resistant to adaptation from a day- to a night-oriented schedule, as determined by a lack of substantial phase shifts over multiple days in centrally controlled rhythms, such as those of melatonin and cortisol. There is evidence that disruption of the circadian system caused by night-shift work results not only in a misalignment between the circadian system and the external light-dark cycle, but also in a state of internal desynchronization between various levels of the circadian system. This is the case between rhythms controlle…

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Circadian Rhythm Sleep-Wake Disorders in Older Adults.

The timing, duration, and consolidation of sleep result from the interaction of the circadian timing system with a sleep-wake homeostatic process. When aligned and functioning optimally, this allows for wakefulness throughout the day and a long consolidated sleep episode at night. Changes to either the sleep regulatory process or how they interact can result in an inability to fall asleep at the desired time, difficulty remaining asleep, waking too early, and/or difficulty remaining awake throughout the day. This mismatch between the desired timing of sleep and the ability to fall asleep and remain asleep is a hallmark of a class of sleep disorders called the circadian rhythm sleep-wake disorders. In this updated article, we discuss typical changes in the circadian regulation of sleep with aging; how age influences the prevalence, diagnosis, and treatment of circadian rhythm sleep disord…

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Precision medicine in circadian rhythm sleep-wake disorders: current state and future perspectives.

In circadian rhythm sleep-wake disorders precision medicine is less developed than in other medical disciplines mainly because homeostatic sleep and circadian timing have a very complex phenotype with multiple genetic regulation mechanisms. However, biomarkers, phenotyping and psychosocial characteristics are increasingly used. Devices for polysomnography, actigraphy and sleep-tracking applications in mobile phones and other consumer devices with eHealth technologies are increasingly used. Also sleep-related questionnaires and the assessment of co-morbidities influencing sleep in circadian rhythm sleep-wake disorders are major contributors to precision sleep medicine. To further strengthen the (pharmaco-)genetic and biomarker pillar, technology needs to be evolved further. Routinely measuring treatment results using patient-reported outcome measures and clinical neurophysiological instru…

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The use of chronobiotics in the resynchronization of the sleep/wake cycle. Therapeutical application in the early phases of Alzheimer's disease.

Treatment of circadian rhythm disorders, whether precipitated by intrinsic factors (e.g., sleep disorders, blindness, mental disorders, aging) or by extrinsic factors (e.g., shift work, jet-lag) has led to the development of a new type of agents called "chronobiotics". The term "chronobiotic" defines a substance displaying the therapeutic activity of shifting the phase or increasing the amplitude of the circadian rhythms. The prototype of this therapeutic group is melatonin, whose administration synchronizes the sleep-wake cycle in blind people and in individuals suffering from circadian rhythm sleep disorders, like delayed sleep phase syndrome, jet lag or shift-work. Daily melatonin production decreases with age, and in several pathologies, attaining its lowest values in Alzheimer's disease (AD) patients. About half of dementia patients have severe disruptions in their sleep-wakefulness…

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Optimising sleep and performance during night float: A systematic review of evidence and implications for graduate medical education trainees.

Graduate medical education (GME) training commonly requires residents and fellows to engage in night float shift work. This review aims to assess the effectiveness of interventions for trainees when preparing for, completing, and recovering from working night float shifts. We reviewed all available studies published prior to September 2019 using PubMed, Scopus, CINAHL, the Cochrane library, PsycINFO, and Google Scholar databases. We included all original, primary research articles assessing either non-pharmacological or pharmacological interventions on the chronobiological and physiological effects of night float shift work among GME trainees. Five studies (n = 179 patients) met inclusion criteria. Interventions included melatonin in the morning before sleep after night float shifts, napping during night float shifts, modafinil after a night of sleep deprivation, and caffeinated energy d…

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Inadequate sleep as a contributor to impaired glucose tolerance: A cross-sectional study in children, adolescents, and young adults with circadian rhythm sleep-wake disorder.

Background: Sleep deprivation and circadian disruption are associated with decreased insulin sensitivity and hyperglycemia. It is uncertain whether circadian sleep-wake disorder (CRSWD), which relates to both the homeostatic sleep system and the circadian timing system, affects glycemic regulation and insulin secretion. We aimed to examine the associations among sleep duration, sleep architecture or circadian rhythm of the sleep-wake cycle, and glucose metabolism in children, adolescents, and young adults with CRSWD. Methods: This cross-sectional observational study of 124 patients with CRSWD took place at Hyogo Children's Sleep and Development Medical Research Center in Hyogo, Japan. The patients underwent a 3-hour oral glucose tolerance test, anthropometric measurements, sleep-log analyses, and polysomnography. Analysis of covariance models were used to assess the association between s…

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Sleep Duration and Sleep Quality in Caregivers of Patients With Dementia: A Systematic Review and Meta-analysis.

Importance: In the United States, 16 million family caregivers provide long-term care for patients with dementia. Although one's physical, mental, and cognitive health depends on sleep, many caregivers experience chronic stress, and stress is typically associated with worse sleep quantity and quality. Objective: To quantify the extent, nature, and treatability of sleep problems in dementia caregivers. Data sources: PubMed and Scopus databases were systematically searched for articles published through June 2018 using the following keywords: caregiver or spouse or caretaker AND sleep or circadian AND dementia or Alzheimer. Backward citation tracking was performed, and corresponding authors were contacted for additional data to conduct meta-analyses and pooled analyses. Study selection: Two reviewers independently screened 805 studies to identify those that reported sleep duration or sleep…

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Adherence and acceptability of light therapies to improve sleep in intrinsic circadian rhythm sleep disorders and neuropsychiatric illness: a systematic review.

Sleep problems and circadian misalignment affect health and well-being and are highly prevalent in those with co-morbid neuropsychiatric disorders. Interventions altering light exposure patterns of affected individuals are a promising non-pharmacological treatment option, shown by previous meta-analyses to improve sleep, and often described as minimally invasive. To best translate laboratory-based mechanistic research into effective treatments, acceptability and barriers to adherence should be understood, but these have not yet been systematically evaluated. Here, we examined evidence regarding adherence and acceptability in studies of light or dark interventions using various delivery devices and protocols to improve sleep in intrinsic circadian rhythm sleep-wake disorders and neuropsychiatric illness. Attrition during intervention was low, and reported experiences were largely positive…

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Multidisciplinary rehabilitation reduces hypothalamic grey matter volume loss in individuals with preclinical Huntington's disease: A nine-month pilot study.

Background: Hypothalamic pathology is a well-documented feature of Huntington's disease (HD) and is believed to contribute to circadian rhythm and habitual sleep disturbances. Currently, no therapies exist to combat hypothalamic changes, nor circadian rhythm and habitual sleep disturbances in HD. Objective: To evaluate the effects of multidisciplinary rehabilitation on hypothalamic volume, brain-derived neurotrophic factor (BDNF), circadian rhythm and habitual sleep in individuals with preclinical HD. Methods: Eighteen individuals with HD (ten premanifest and eight prodromal) undertook a nine-month multidisciplinary rehabilitation intervention (intervention group), which included exercise, cognitive and dual task training and social events, and were compared to a community sample of eleven individuals with premanifest HD receiving no intervention (control group). Hypothalamic volume, ser…

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Chronobiological disorders: current and prevalent conditions.

In recent decades, the hectic lifestyle of industrialized societies has wrought its effects on the quality of sleep, and these effects are evidenced by a profusion of sleep-related disorders. Regular exposure to artificial light, coupled with social and economic pressures have shortened the time spent asleep. Otherwise, Circadian Rhythm Sleep Disorders are characterized by desynchronization between the intrinsic circadian clock and the extrinsic cycles of light/dark and social activities. This desynchronization produces excessive sleepiness and insomnia. The International Classification of Sleep Disorders describes nine sleep disorders under the category of Circadian Rhythm Sleep Disorders. Currently, this diagnosis is made based on the patient's history, a sleep log alone, or the sleep logs and actigraphy conducted for at least 7 days. This review contains an overview of current treatme…

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Entrainment of the human circadian pacemaker to longer-than-24-h days.

Entrainment of the circadian pacemaker to the light:dark cycle is necessary for rhythmic physiological functions to be appropriately timed over the 24-h day. Nonentrainment results in sleep, endocrine, and neurobehavioral impairments. Exposures to intermittent bright light pulses have been reported to phase shift the circadian pacemaker with great efficacy. Therefore, we tested the hypothesis that a modulated light exposure (MLE) with bright light pulses in the evening would entrain subjects to a light:dark cycle 1 h longer than their own circadian period (tau). Twelve subjects underwent a 65-day inpatient study. Individual subject's circadian period was determined in a forced desynchrony protocol. Subsequently, subjects were released into 30 longer-than-24-h days (daylength of tau + 1 h) in one of three light:dark conditions: (i) approximately 25 lux; (ii) approximately 100 lux; and (ii…

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The Emerging Circadian Phenotype of Borderline Personality Disorder: Mechanisms, Opportunities and Future Directions.

Purpose of review: We review the recent evidence suggesting that circadian rhythm disturbance is a common unaddressed feature of borderline personality disorder (BPD); amelioration of which may confer substantial clinical benefit. We assess chronobiological BPD studies from a mechanistic and translational perspective and highlight opportunities for the future development of this hypothesis. Recent findings: The emerging circadian phenotype of BPD is characterised by a preponderance of comorbid circadian rhythm sleep-wake disorders, phase delayed and misaligned rest-activity patterns and attenuated amplitudes of usually well-characterised circadian rhythms. Such disturbances may exacerbate symptom severity, and specific maladaptive personality dimensions may produce a liability towards extremes in chronotype. Pilot studies suggest intervention may be beneficial, but development is limited…

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Afternoon nap and bright light exposure improve cognitive flexibility post lunch.

Beneficial effects of napping or bright light exposure on cognitive performance have been reported in participants exposed to sleep loss. Nonetheless, few studies investigated the effect of these potential countermeasures against the temporary drop in performance observed in mid-afternoon, and even less so on cognitive flexibility, a crucial component of executive functions. This study investigated the impact of either an afternoon nap or bright light exposure on post-prandial alterations in task switching performance in well-rested participants. Twenty-five healthy adults participated in two randomized experimental conditions, either wake versus nap (n=15), or bright light versus placebo (n=10). Participants were tested on a switching task three times (morning, post-lunch and late afternoon sessions). The interventions occurred prior to the post-lunch session. In the nap/wake condition,…

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Long-term effectiveness outcome of melatonin therapy in children with treatment-resistant circadian rhythm sleep disorders.

To date, there have been no prospective long-term studies of melatonin therapy in children. We report here data from a prospective follow-up study of 44 children with neurodevelopmental disabilities and treatment-resistant circadian rhythm sleep disorders (CRSD) who had participated in a placebo controlled, double blind cross-over trial of sustained-release melatonin. The follow-up study involved a structured telephone interview of caregivers every 3 months for upto 3.8 yr. The caregivers provided ratings of satisfaction, adverse effects, benefits, persistence with treatment and additional medications. Changes in melatonin dose were recorded. Open ended questions were included to capture caregivers' impressions and comments concerning melatonin therapy. Adverse reaction to melatonin therapy and development of tolerance were not evident. Better sleep was associated with reported improveme…

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Beneficial Effects of Time-Restricted Eating on Metabolic Diseases: A Systemic Review and Meta-Analysis.

Various behavioral and physiological pathways follow a pre-determined, 24 hour cycle known as the circadian rhythm. Metabolic homeostasis is regulated by the circadian rhythm. Time-restricted eating (TRE) is a type of intermittent fasting based on the circadian rhythm. In this study, we aim to analyze systemically the effects of TRE on body weight, body composition, and other metabolic parameters. We reviewed articles from PubMed, EMBASE, and the Cochrane Library to identify clinical trials that compared TRE to a regular diet. We included 19 studies for meta-analysis. Participants following TRE showed significantly reduced body weight (mean difference (MD), -0.90; 95% confidence interval (CI): -1.71 to -0.10) and fat mass (MD: -1.58, 95% CI: -2.64 to -0.51), while preserving fat-free mass (MD, -0.24; 95% CI: -1.15 to 0.67). TRE also showed beneficial effects on cardiometabolic parameters…

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Psychological and behavioural interventions in bipolar disorder that target sleep and circadian rhythms: A systematic review of randomised controlled trials.

Sleep and circadian disruptions are prominent symptoms of bipolar disorder (BD) and potential targets for adjunctive interventions. The aim of this review was to appraise the effectiveness of psychological and behavioural interventions in BD that target sleep and circadian rhythms, as reported by randomised controlled trials. Nineteen studies met the inclusion/exclusion criteria. They were summarised via narrative synthesis and meta-analysis wherever appropriate. Six studies delivered bright light therapy, five interpersonal and social rhythm therapy, two blue-light blocking glasses, one cognitive behavioural therapy for insomnia, one total sleep deprivation, and four combination treatments. More than half of the studies (N = 10, 52 %) did not measure sleep or circadian rhythms despite being the principal target of the intervention. Overall, the evidence base for the effectiveness of the…

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Shift work sleep disorder.

Shift work sleep disorder (SWSD) is a circadian rhythm sleep-wake disorders affecting individuals who work in nonstandard hours, particularly night shifts. It manifests as difficulty sleeping during the day and staying awake during work hours, leading to health issues. SWSD is not universally experienced by all shift workers, with about 30% affected. Diagnosing SWSD involves monitoring sleep patterns and differentiating it from other disorders such as sleep apnea. Prevention and treatment include collective measures such as optimizing shift schedules and individual strategies such as sleep/circadian hygiene, light therapy, melatonin use, and, if necessary, prescription medications. Despite these interventions, the primary recommendation is to switch to daytime work, although this may not be feasible for all workers.

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