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

Sleep in autism: A biomolecular approach to aetiology and treatment.

People with autism spectrum disorder (ASD) commonly experience other comorbidities. Studies indicate that between 50% and 83% of individuals with ASD have sleep problems or disorders. The most commonly reported sleep problems are: (a) insomnia symptoms including the inability to get to sleep or stay asleep; and (b) circadian rhythm sleep-wake disorders, defined as a misalignment between the timing of endogenous circadian rhythms and the external environment. The circadian system provides timing information for the sleep-wake cycle that is regulated by the interaction of an endogenous processes (circadian - Process C, and homeostatic - Process S) and synchronizing agents (neurohormones and neurotransmitters), which produce somnogenic activity. A clinical priority in ASD is understanding the cause of these sleep problems in order to improve treatment outcomes. This review approaches sleep …

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Working Time Society consensus statements: Evidence-based effects of shift work on physical and mental health.

Potential effects of shift work on health are probably related to the misalignment between the light-dark cycle and the human activity-rest cycle. Light exposure at night mediates these effects, including social misalignment and leads to an inversion of activity and rest, which, in turn, is linked to changes in behaviours. This article reviews the epidemiological evidence on the association between shift work and health, and possible mechanisms underlying this association. First, evidence from findings of the meta-analyses and systematic reviews published in the last 10 yr is presented. In addition, it reports the larger single-occupation studies and recent large population-based studies of the general workforce. Koch's postulates were used to evaluate the evidence related to the development of disease as a result of exposure to shift work. Finally, we discussed limitations of the multip…

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Drugs Used in Circadian Sleep-Wake Rhythm Disturbances.

This article focuses on melatonin and other melatonin receptor agonists, and specifically their circadian phase shifting and sleep-enhancing properties. The circadian system and circadian rhythm sleep-wake disorders are briefly reviewed, followed by a summary of the circadian phase shifting, sleep-enhancing properties, and possible safety concerns associated with melatonin and other melatonin receptor agonists. The recommended use of melatonin, including dose and timing, in the latest American Academy of Sleep Medicine Clinical Practice Guidelines for the treatment of intrinsic circadian rhythm disorders is also reviewed. Lastly, the practical aspects of treatment and consideration of clinical treatment outcomes are discussed.

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Circadian System and Glucose Metabolism: Implications for Physiology and Disease.

The circadian system serves one of the most fundamental properties present in nearly all organisms: it generates 24-h rhythms in behavioral and physiological processes and enables anticipating and adapting to daily environmental changes. Recent studies indicate that the circadian system is important in regulating the daily rhythm in glucose metabolism. Disturbance of this circadian control or of its coordination relative to the environmental/behavioral cycle, such as in shift work, eating late, or due to genetic changes, results in disturbed glucose control and increased type 2 diabetes risk. Therefore, an in-depth understanding of the mechanisms underlying glucose regulation by the circadian system and its disturbance may help in the development of therapeutic interventions against the deleterious health consequences of circadian disruption.

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Neurophysiology of circadian rhythm sleep disorders of children with neurodevelopmental disabilities.

This article reviews circadian rhythm sleep disorders (CRSDs) of children with neurodevelopmental disabilities. These sleep disturbances frequently occur in this population but they are misunderstood and under diagnosed. The causes and features of CRSD in children with brain disorders differ in many ways from those seen in typically developing children. It is the brain, including the eyes, which regulates sleep and circadian rhythmicity by modulating pineal melatonin production/secretion and when there is significant brain damage, the sleep/wake patterns may be modified. In most instances CRSD are not disorders of the suprachiasmatic nuclei because these small hypothalamic structures only adjust their functions to the changing photic and non-photic modulatory influences. Each form of CRSD is accompanied by characteristic changes in serum melatonin levels and clinical features. When noctu…

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Melatonin agonists and insomnia.

The ability of melatonin to shift biological rhythms is well known. As a result, melatonin has been used in the treatment of various circadian rhythm sleep disorders, such as advanced and delayed sleep phase disorders, jet lag and shiftwork disorder. The current evidence for melatonin being efficacious in the treatment of primary insomnia is less compelling. The development of agents that are selective for melatonin receptors provides opportunity to further elucidate the actions of melatonin and its receptors and to develop novel treatments for specific types of sleep disorders. The agonists reviewed here - ramelteon, tasimelteon and agomelatine - all appear to be efficacious in the treatment of circadian rhythm sleep disorders and some types of insomnia. However, further studies are required to understand the mechanisms of action, particularly for insomnia. Clinical application of the a…

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Jet lag, circadian rhythm sleep disturbances, and depression: the role of melatonin and its analogs.

Traveling through several time zones results in a constellation of symptoms known as jet lag. These include reduced alertness, daytime fatigue, loss of appetite, reduced cognitive skills, and disruption of the sleep/wake cycle. In susceptible air travel passengers, jet lag may exacerbate affective illness and result in psychiatric morbidity. Dysregulation of circadian rhythms and melatonin secretion represent the common underlying factor in jet lag and other circadian disorders. Recent studies have established the effectiveness of strategically timed administration of melatonin and appropriate timed exposure to environmental schedules including light in counteracting the dysregulation (chronobiologic actions). With the introduction of melatonergic agonists such as ramelteon and tasimelteon, which have both a stronger affinity for MT₁ and MT₂ melatonin receptors and a longer half-life, ne…

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Defining chronodisruption.

When the International Agency for Research on Cancer (IARC) classified shift-work that involves circadian disruption as probably carcinogenic to humans in 2007, this was the prelude to extensive experimental and epidemiological research in coming years. Indeed, with some 20% of people worldwide being engaged in some type of work at unusual times, including the night, it is a must to investigate, and to clarify as soon as possible, the biologically plausible links via circadian disruption with epidemic cancers such as of the breast or prostate. Surprisingly, neither the IARC information available so far nor the general literature provides a clear definition of what the critical component in the postulated chain of causation, namely circadian disruption, is. Here we offer our definition of chronodisruption (CD), a concept which we proposed in 2003 and which we operationalized recently in r…

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The role of the thalamus in sleep, pineal melatonin production, and circadian rhythm sleep disorders.

The thalamus has a strong nonphotic influence on sleep, circadian rhythmicity, pineal melatonin production, and secretion. The opening of the sleep gate for nonrapid eye movement sleep is a thalamic function but it is assisted by melatonin which acts by promoting spindle formation. Thus, melatonin has a modulatory influence on sleep onset and maintenance. A remarkable similarity exists between spindle behavior, circadian rhythmicity, and pineal melatonin production throughout life. Together, the thalamic and chronobiological control of sleep leads to a new and improved understanding of the pathophysiology of circadian rhythm sleep disorders and also of the principles of sleep hygiene interventions.

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Parkinson's disease as a neuroendocrine disorder of circadian function: dopamine-melatonin imbalance and the visual system in the genesis and progression of the degenerative process.

For more than 50 years, Parkinson's disease (PD) has been conceptualized as a product of nigro-striatal dopamine (NSD) system degeneration. In spite of a growing body of evidence depicting the mammalian brain as an interrelated complexity of circuitous systems, dopamine (DA) deficiency of the NSD is still regarded as the main problem, with DA replacement being the purpose of therapeutic intervention. For at least 191 years circadian involvement in various aspects of PD, including depression and insomnia, has been recognized as an integral part of the symptom matrix of PD and yet attempts to elucidate the involvement of this system is uncharted territory. The present review attempts a major reorganization of mammalian brain into a coordinated complex involving the NSD and the retinal hypothalamic tract (RHT) as the primary systems involved in the retino-diencephalic/mesencephalic-pineal (…

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Jet lag: therapeutic use of melatonin and possible application of melatonin analogs.

Each year millions of travelers undertake long distance flights over one or more continents. These multiple time zone flights produce a constellation of symptoms known as jet lag. Familiar to almost every intercontinental traveler is the experience of fatigue upon arrival in a new time zone, but almost as problematic are a number of other jet lag symptoms. These include reduced alertness, nighttime insomnia, loss of appetite, depressed mood, poor psychomotor coordination and reduced cognitive skills, all symptoms which are closely affected by both the length and direction of travel. The most important jet lag symptoms are due to disruptions to the body's sleep/wake cycle. Clinical and pathophysiological studies also indicate that jet lag can exacerbate existing affective disorders. It has been suggested that dysregulation of melatonin secretion and occurrence of circadian rhythm disturba…

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Melatonin receptors: role on sleep and circadian rhythm regulation.

The circadian release of the hormone melatonin is regulated by the suprachiasmatic nucleus (SCN), which feeds back into the nucleus to modulate sleep and circadian phase through activation of the MT(1) and/or MT(2) melatonin receptors. Considering the functions of the SCN as a sleep and circadian rhythm regulator, melatonin and melatonin receptor agonists have attracted interest as being possible treatments for sleep and circadian rhythm sleep disorders. Part of this interest has centered on elucidating which melatonin receptors are targets for the regulation of these functions within the SCN. Two G-protein coupled melatonin receptors, the MT(1) and MT(2), inhibit neuronal activity and phase shift circadian firing rhythms in the SCN, respectively. Recent reports have uncovered possible interactions between the two types of receptors in the mammalian SCN, as well as the role of physiologi…

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Improvement of a patient's circadian rhythm sleep disorders by aripiprazole was associated with stabilization of his bipolar illness.

Splitting of the behavioural activity phase has been found in nocturnal rodents with suprachiasmatic nucleus (SCN) coupling disorder. A similar phenomenon was observed in the sleep phase in the diurnal human discussed here, suggesting that there are so-called evening and morning oscillators in the SCN of humans. The present case suffered from bipolar disorder refractory to various treatments, and various circadian rhythm sleep disorders, such as delayed sleep phase, polyphasic sleep, separation of the sleep bout resembling splitting and circabidian rhythm (48 h), were found during prolonged depressive episodes with hypersomnia. Separation of sleep into evening and morning components and delayed sleep-offset (24.69-h cycle) developed when lowering and stopping the dose of aripiprazole (APZ). However, resumption of APZ improved these symptoms in 2 weeks, accompanied by improvement in the p…

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The melatonin receptor agonist is effective for free-running type circadian rhythm sleep disorder: case report on two sighted patients.

Along with urbanization of the living environment, the number of patients with circadian rhythm sleep disorder (CRSD) has been increasing. There are several treatment candidates for CRSD, such as light therapy, drugs (melatonin and vitamin B12), and sleep hygiene education. However, successful treatment method has not been established. In free-running type (FRT) CRSD, the endogenous circadian rhythm cannot be entrained to the 24-h light-dark cycle, resulting in free running on a cycle 0.5-2.5 h longer than the 24-h period. This condition is relatively common in blind individuals and is unusual in sighted individuals. Here we report two sighted patients with FRT, successfully treated with a melatonin receptor agonist, ramelteon. Patient 1 (36-year-old female) had suffered from FRT for nearly 4 months after resigning her job. She was given sleep hygiene education together with ramelteon at…

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Evaluation of a brief treatment program of cognitive behavior therapy for insomnia in older adults.

Objective: To evaluate the efficacy of a brief 4-w group-administered treatment program of cognitive behavior therapy for insomnia (CBT-I) for older adults with sleep maintenance insomnia. Design: Randomized controlled trial of CBT-I compared to waitlist control with comparisons at pretreatment, posttreatment, and 3-mo follow-up. Setting: Flinders University Sleep and Circadian Rhythm Research Laboratory, Adelaide, South Australia. Participants: One-hundred eighteen adults with sleep maintenance insomnia (mean age = 63.76 y, standard deviation = 6.45 y, male = 55). Interventions: A 4-w, group-based treatment program of CBT-I including bedtime restriction therapy, sleep education, and cognitive restructuring. Measurements: Seven-day sleep diaries, actigraphy, and several self-report measures to assess perceived insomnia severity, daytime functioning, and confidence in and beliefs about sl…

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Acute sleep deprivation: the effects of the AMPAKINE compound CX717 on human cognitive performance, alertness and recovery sleep.

AMPA receptor modulation is a potential novel approach to enhance cognitive performance. CX717 is a positive allosteric modulator of the AMPA receptor that has shown efficacy in rodent and primate cognition models. CX717 (100 mg, 300 mg and 1000 mg) and placebo were studied in 16 healthy male volunteers (18-45 years) in a randomized, crossover study. Cognitive function, arousal and recovery sleep (by polysomnography) were assessed during the extended wakefulness protocol. Placebo condition was associated with significant decrements in cognition, particularly at the circadian nadir (between 03:00 and 05:00). Pre-specified primary and secondary analyses (general linear mixed modelling, GLMM) at each separate time point did not reveal consistent improvements in performance or objective alertness with any dose of CX717. Exploratory repeated measures analysis, a method used to take into accou…

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A phase 3, double-blind, randomized, placebo-controlled study of armodafinil for excessive sleepiness associated with jet lag disorder.

Objective: To assess the effect of armodafinil, the longer-lasting isomer of modafinil, on jet lag disorder. Participants and methods: This double-blind, randomized, parallel-group, multicenter study was conducted between September 18, 2008, and February 9, 2009. Adults with a history of jet lag symptoms on previous flights through multiple time zones flew from the United States to France (a 6-hour time zone change) for a 3-day laboratory-based study period. Participants received armodafinil (50 or 150 mg/d) or placebo each morning. Wakefulness was assessed by the coprimary outcomes, mean sleep latency on the Multiple Sleep Latency Test (MSLT) (average of all MSLT sessions across days 1 and 2) and Patient Global Impression of Severity in relation to jet lag symptoms (averaged across days 1 and 2). Results: A total of 427 participants received armodafinil at 50 mg/d (n=142), armodafinil a…

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Interconnection between circadian clocks and thyroid function.

Circadian rhythmicity is an approximately 24-h cell-autonomous period driven by transcription-translation feedback loops of specific genes, which are referred to as 'circadian clock genes'. In mammals, the central circadian pacemaker, which is located in the hypothalamic suprachiasmatic nucleus, controls peripheral circadian clocks. The circadian system regulates virtually all physiological processes, which are further modulated by changes in the external environment, such as light exposure and the timing of food intake. Chronic circadian disruption caused by shift work, travel across time zones or irregular sleep-wake cycles has long-term consequences for our health and is an important lifestyle factor that contributes to the risk of obesity, type 2 diabetes mellitus and cancer. Although the hypothalamic-pituitary-thyroid axis is under the control of the circadian clock via the suprachi…

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Timing of light exposure affects mood and brain circuits.

Temporal organization of physiology is critical for human health. In the past, humans experienced predictable periods of daily light and dark driven by the solar day, which allowed for entrainment of intrinsic circadian rhythms to the environmental light-dark cycles. Since the adoption of electric light, however, pervasive exposure to nighttime lighting has blurred the boundaries of day and night, making it more difficult to synchronize biological processes. Many systems are under circadian control, including sleep-wake behavior, hormone secretion, cellular function and gene expression. Circadian disruption by nighttime light perturbs those processes and is associated with increasing incidence of certain cancers, metabolic dysfunction and mood disorders. This review focuses on the role of artificial light at night in mood regulation, including mechanisms through which aberrant light expo…

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Efficacy of brief behavioural therapy for insomnia in older adults with chronic insomnia: a systematic review and meta-analysis from randomised trials.

Background: chronic insomnia is a highly prevalent and persistent health concern among older adults, and it has significant adverse effects on cognitive function and physical health. Objectives: the study aimed to evaluate the efficacy of a brief 4-week behavioural therapy for insomnia (BBTi) on insomnia remission in older adults with chronic insomnia. Design: a systematic review and meta-analysis were conducted. Subjects: adults aged 60 years or older. Methods: eight electronic databases were systematically searched through the end of March 2022. Studies followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Statement. Results: four randomised controlled trials (190 subjects) were included. The mean age of the participants was 69.06 (65.10-71.65), and 29.9% (27.3-32.3%) were male. Older adults who received the BBTi showed a significant insomnia remission (standa…

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Sleep duration and risk for hypertension in women: results from the nurses' health study.

Background: Acute sleep restriction has been shown to increase blood pressure and sympathetic nervous system activity. Methods: We investigated the relationships between sleep duration and hypertension among women whose sleep durations were self-reported in 1986 (n = 82,130) and 2000 (n = 71,658) in the Nurses' Health Study I (NHS-I) and in 2001 (n = 84,674) in the Nurses' Health Study II (NHS-II). Results: After controlling for multiple risk factors in logistic regression models, the prevalence of hypertension was significantly higher among women in all 3 groups who slept ≤5 hours (odds ratio = 1.19, 95% confidence interval [CI] = 1.14-1.25) per night compared with 7 hours. In prospective analyses using Cox regression shorter sleep duration of ≤5 hours per night was significantly associated with a higher incidence of hypertension only in younger women (hazard ratio [HR] =1.20, 95% CI = …

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Clinical practice guidelines for switching or deprescribing hypnotic medications for chronic insomnia: Results of European neuropsychopharmacology and sleep expert's consensus group.

Introduction: Current guidelines recommend cognitive behavioural therapy for insomnia (CBT-I) as the first-line treatment for chronic insomnia. Pharmacological recommendations by European guidelines for the treatment of insomnia disorder include positive GABAergic modulators such as short and medium acting benzodiazepines and "Z-drugs" (eszopiclone, zaleplon, zolpidem, zopiclone), dual orexin receptor antagonists (DORAs; daridorexant), melatonin receptor agonists (melatonin 2 mg prolonged release - PR). Given the chronic nature of insomnia, the presence of non-responders to some treatments it is often necessary switching between various therapeutic approaches and medications. However, clear guidance regarding safe and effective protocols for switching these medications currently lacks in Europe. Method: To address this gap, we used the RAND/UCLA Appropriateness to evaluate the appropriat…

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Colorimetric sensing assay based on aptamer-gold nanoparticles for rapid detection of salivary melatonin to monitor circadian rhythm sleep disorders.

Salivary melatonin is a clinically used biomarker for diagnosing circadian rhythm sleep disorders. Current melatonin detection assays are complex, expensive, and in many cases do not adequately measure low levels of salivary melatonin. Precisely measuring melatonin levels at multiple time points is crucial for determining dim light melatonin onset to evaluate its circadian fluctuation as well as the extent of circadian disruption and consequently adapt treatment regimens. Moreover, melatonin low levels in saliva challenges the reliability of routine clinical testing. This paper presents the development of a novel, highly sensitive, yet cost-effective, colorimetric assay for the rapid detection of salivary melatonin utilizing aptamer-AuNPs. Among several types of the aptamer tested, the 36-mer MLT-A-2 aptamer-AuNP probe showed the highest sensitivity with a melatonin limit of detection of…

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Serum concentrations of insulin-like growth factor-1 as a biomarker of improved circadian rhythm sleep-wake disorder in school-aged children.

Study objectives: We aimed to investigate whether improvements in the symptoms of circadian rhythm sleep-wake disorder after treatment were associated with an increase in serum insulin-like growth factor-1 (IGF-1) concentration. Methods: Eighty-seven school-aged children (32 males, 55 females), aged 14.31 ± 1.50 years (mean ± standard deviation), who were admitted to our hospital with circadian rhythm sleep-wake disorder received treatment for 6-8 weeks consisting of the following protocol: (1) lights-out for sleep occurred at 21:00, (2) phototherapy for waking started at 06:00 or 07:00, and (3) light exercise was required every day (eg, a 20- to 30-minute walk). Blood samples were collected at 08:00 am to measure the serum concentrations of IGF-1, pre- and posttreatment. Results: The mean times of day of sleep onset and offset at the pre- and posttreatment timepoints were 23:32 ± 4.21 a…

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Clinical Sleep-Wake Disorders II: Focus on Insomnia and Circadian Rhythm Sleep Disorders.

Insomnia and circadian rhythm sleep disorders affect large proportions of the population and have pronounced effects on quality of life and daytime performance. While the neurobiology of insomnia is not yet fully understood, circadian rhythm sleep disorders are assumed to be caused by a mismatch between the individual circadian phase position and the desired sleep-wake schedule. Benzodiazepines and non-benzodiazepine positive allosteric GABAA receptor modulators improve sleep onset and maintenance in the short-term treatment of insomnia. However, tolerance and dependence are important side effects. Sedating antidepressants are frequently prescribed for insomnia, however, only few randomised controlled trials have been published so far. Melatonin and melatonin receptor agonists are considered to be an option for the treatment of insomnia especially because of their minimal abuse potential…

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