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

The Munich ChronoType Questionnaire for Shift-Workers (MCTQShift).

Sleep is systematically modulated by chronotype in day-workers. Therefore, investigations into how shift-work affects sleep, health, and cognition may provide more reliable insights if they consider individual circadian time (chronotype). The Munich ChronoType Questionnaire (MCTQ) is a useful tool for determining chronotype. It assesses chronotype based on sleep behavior, specifically on the local time of mid-sleep on free days corrected for sleep debt accumulated over the workweek (MSFsc). Because the original MCTQ addresses people working standard hours, we developed an extended version that accommodates shift-work (MCTQ(Shift)). We first present the validation of this new version with daily sleep logs (n = 52) and actimetry (n = 27). Next, we evaluated 371 MCTQ(Shift) entries of shift-workers (rotating through 8-h shifts starting at 0600 h, 1400 h, and 2200 h). Our results support exp…

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Sleep-Wake Disturbance Related to Ocular Disease: A Systematic Review of Phase-Shifting Pharmaceutical Therapies.

Purpose: Light input, via the eyes, is essential for regulating circadian rhythms. Eye diseases can cause disruption of vital biological rhythms. Of totally blind people, 87% report sleep problems. There are no UK guidelines for visual disturbance-related circadian rhythm disruption. Our objective was to systematically review the literature to determine the effectiveness of pharmacological agents on the sleep quality of patients with sleep disturbance related to ocular disease. Methods: We searched CENTRAL, MEDLINE, EMBASE, PsycINFO, and CINAHL alongside protocol registries and citation searches. We assessed the risk of bias using the Cochrane Risk of Bias Assessment Tool and assessed the strength of overall evidence using GRADE criteria. Results: Four studies (n=116) met the inclusion criteria. Low-quality evidence showed that melatonin can cause entrainment (1 study), increases in tota…

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Delayed sleep-wake phase disorder.

Delayed sleep-wake phase disorder (DSWPD) is the most commonly encountered of the circadian rhythm sleep-wake disorders (CRSDs), and is often confused with sleep initiation insomnia. It typically emerges in teenage years and persists into adulthood. In essence, people with the disorder have an abnormally delayed major sleep episode relative to the dark phase of the solar cycle, and hence great difficulty initiating sleep at an appropriately early time, and, as a knock-on effect, waking at a desirable time in the morning, leading to chronic, and often quite severe sleep restriction trying to conform to a 9 to 5 schedule. As a result, sleep on free days is often extended in compensation. When released from such schedule constraints, sleep duration and quality is normal; it is just delayed. This review highlights elements of our current understanding of the epidemiology, associations and pa…

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Circadian Rhythm Sleep-Wake Disorders.

Objective: This article provides an overview of advances in the understanding of circadian rhythms and the health implications of circadian disruption. Latest developments: Circadian medicine is a relatively new concept, with widespread overlap with many other areas of medicine. Circadian clocks rely on feedback loops that control the expression of many genes. Functional circadian oscillators exist at multiple physiologic levels and facilitate a multimodal clock mechanism. The suprachiasmatic nucleus is the central circadian pacemaker. Peripheral tissues can be entrained by other stimuli (such as food intake) and can uncouple from the suprachiasmatic nucleus pacemaker; this discovery may provide new therapeutic options for circadian rhythm disorders. Numerous modern developments have altered our circadian clocks and these changes are associated with poor health outcomes. Essential points…

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Prevalence and associated factors of circadian rhythm sleep-wake disorders and insomnia among visually impaired Japanese individuals.

Background: Although earlier studies have demonstrated that circadian rhythm sleep-wake disorders (CRSWD) are more prevalent in visually impaired individuals, the actual prevalence of CRSWD and insomnia among the visually impaired Japanese population remains unclear. The aim of this cross-sectional, telephone-based study was to estimate the prevalence of CRSWD and insomnia, and explore factors associated with CRSWD and insomnia among visually impaired Japanese individuals. Methods: A nationwide telephone survey was conducted among visually-impaired individuals through local branches of the Japan Federation of the Blind. In total, 157 visually impaired individuals were eligible for this study. Demographic information and information about visual impairments, lifestyle, and sleep patterns were assessed using questionnaires and subsequent telephone interviews. CRSWD and insomnia were define…

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Core body temperature changes in school-age children with circadian rhythm sleep-wake disorder.

Objective/background: Core body temperature (CBT) is considered a valuable marker for circadian rhythm. This study aimed to investigate the changes in CBT that are associated with the symptoms of circadian rhythm sleep-wake disorder (CRSWD) post-treatment in children. Patients/methods: Twenty-eight school-age children [10 boys and 18 girls; mean age (±standard deviation), 13.68 ± 0.93 years] who were admitted to our hospital with CRSWD underwent treatment for 6-8 weeks according to the following protocol: lights-out for sleep at 21:00; phototherapy for waking at 6:00 or 7:00; light exercise everyday (eg, a 20- to 30-min walk). CBT was continuously measured for 24 h on the first day of admission and on the first day after treatment. Results: The mean time of sleep onset/offset (±standard deviation; in hours:minutes) 1 week before admission and 1 week after treatment were 23:53 ± 2:26/9:58…

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Sleep, circadian rhythm, and physical activity patterns in depressive and anxiety disorders: A 2-week ambulatory assessment study.

Background: Actigraphy may provide a more valid assessment of sleep, circadian rhythm (CR), and physical activity (PA) than self-reported questionnaires, but has not been used widely to study the association with depression/anxiety and their clinical characteristics. Methods: Fourteen-day actigraphy data of 359 participants with current (n = 93), remitted (n = 176), or no (n = 90) composite international diagnostic interview depression/anxiety diagnoses were obtained from the Netherlands Study of Depression and Anxiety. Objective estimates included sleep duration (SD), sleep efficiency, relative amplitude (RA) between day-time and night-time activity, mid sleep on free days (MSF), gross motor activity (GMA), and moderate-to-vigorous PA (MVPA). Self-reported measures included insomnia rating scale, SD, MSF, metabolic equivalent total, and MVPA. Results: Compared to controls, individuals w…

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Adolescents at clinical-high risk for psychosis: Circadian rhythm disturbances predict worsened prognosis at 1-year follow-up.

Background: Individuals with psychotic disorders experience disruptions to both the sleep and circadian components of the sleep/wake cycle. Recent evidence has supported a role of sleep disturbances in emerging psychosis. However, less is known about how circadian rhythm disruptions may relate to psychosis symptoms and prognosis for adolescents with clinical high-risk (CHR) syndromes. The present study examines circadian rest/activity rhythms in CHR and healthy control (HC) youth to clarify the relationships among circadian rhythm disturbance, psychosis symptoms, psychosocial functioning, and the longitudinal course of illness. Methods: Thirty-four CHR and 32 HC participants were administered a baseline evaluation, which included clinical interviews, 5days of actigraphy, and a sleep/activity diary. CHR (n=29) participants were re-administered clinical interviews at a 1-year follow-up ass…

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Evaluation of circadian phenotypes utilizing fibroblasts from patients with circadian rhythm sleep disorders.

We evaluated the circadian phenotypes of patients with delayed sleep-wake phase disorder (DSWPD) and non-24-hour sleep-wake rhythm disorder (N24SWD), two different circadian rhythm sleep disorders (CRSDs) by measuring clock gene expression rhythms in fibroblast cells derived from individual patients. Bmal1-luciferase (Bmal1-luc) expression rhythms were measured in the primary fibroblast cells derived from skin biopsy samples of patients with DSWPD and N24SWD, as well as control subjects. The period length of the Bmal1-luc rhythm (in vitro period) was distributed normally and was 22.80±0.47 (mean±s.d.) h in control-derived fibroblasts. The in vitro periods in DSWPD-derived fibroblasts and N24SWD-derived fibroblasts were 22.67±0.67 h and 23.18±0.70 h, respectively. The N24SWD group showed a significantly longer in vitro period than did the control or DSWPD group. Furthermore, in vitro peri…

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Circadian rhythm sleep-wake disorders as predictors for bipolar disorder in patients with remitted mood disorders.

Background: Circadian rhythm dysfunction is thought to play a key role in the pathogenesis of bipolar disorder (BD). We focused on circadian rhythm sleep-wake disorders (CRSWD) as possible predictors for bipolar disorder in patients with remitted mood disorders. Method: One hundred four BD (41 type I and 63 type II) outpatients and 73 age- and sex-matched major depressive disorder (MDD) outpatients participated in this study. The subjects were asked to answer questionnaires including demographic variables, clinical course of the disorder, and family history of psychiatric disorders. Severity of mood status was evaluated by the Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale. CRSWD was diagnosed by clinical interview and sleep logs based on the International Classification of Sleep Disorders, third edition. Results: The rate of CRSWD in BD subjects was significantly…

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Estimation methods for human circadian phase by use of peripheral tissues.

Almost all living organisms, including humans, exhibit diurnal rhythms of physiology and behavior, which are driven by the circadian clock. Many studies have found that chronic misalignment between circadian and environmental/social rhythms carries a significant risk of various disorders, including sleep disorders, metabolic syndrome, cardiovascular diseases and cancer. However, irregular sleep-wake cycles and circadian maladjustment often cause 'social jet lag', which is minor but chronic jet-lag in our daily lives. Establishment of objective and convenient circadian-phase estimation methods in the clinical setting would therefore greatly contribute not only to resolving this global health problem but also to developing chronomedicine, a clinical approach for optimizing the time of day of treatments. Traditional melatonin-based methods have limitations with respect to circadian-phase ev…

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Health impact of fasting in Saudi Arabia during Ramadan: association with disturbed circadian rhythm and metabolic and sleeping patterns.

Background: Muslims go through strict Ramadan fasting from dawn till sunset for one month yearly. These practices are associated with disturbed feeding and sleep patterns. We recently demonstrated that, during Ramadan, circadian cortisol rhythm of Saudis is abolished, exposing these subjects to continuously increased cortisol levels. Hypothesis: Secretory patterns of other hormones and metabolic parameters associated with cortisol, and insulin resistance, might be affected during Ramadan. Protocol: Ramadan practitioners (18 males, 5 females; mean age ±SEM = 23.16±1.2 years) were evaluated before and two weeks into Ramadan. Blood was collected for measurements of endocrine and metabolic parameters at 9 am (±1 hour) and again twelve hours later. Results: In Ramadan, glucose concentration was kept within normal range, with a significant increase in the morning. Mean morning concentration of…

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Rotating shift work and menstrual cycle characteristics.

Background: Shift workers who experience sleep disturbances and exposure to light at night could be at increased risk for alterations in physiologic functions that are circadian in nature. Methods: We investigated rotating shift work and menstrual cycle patterns in the Nurses' Health Study II using cross-sectional data collected in 1993 from 71,077 nurses aged 28-45 years who were having menstrual periods and were not using oral contraceptives. Log-binomial regression was used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Results: Eight percent of participants reported working rotating night shifts for 1-9 months, 4% for 10-19 months, and 7% for 20+ months during the previous 2 years. Irregular cycles (>7 days variability) were reported by 10% of participants. Seventy percent of women reported menstrual cycles of 26-31 days, 1% less than 21 days, 16% 21-25 days, 11…

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Shiftwork impacts and adaptation among health care workers.

Background: Shiftwork among health care workers impacts upon the safety and health of both employees and patients. Aims: To characterize shiftwork-related attitudes, behaviours, symptoms and coping strategies among health care workers, two validated questionnaires (the Standard Shiftwork Index and the Pressure Management Indicator) were used to identify factors predicting shiftwork adaptation. Methods: Participants (n = 376, response rate 25%) were grouped according to their work schedule (days, permanent evenings, rotating days plus evenings, permanent nights or relief and combined shifts). Indicators of lifestyle, work organization, sleep disruption, health and pressure management among workers on irregular shifts were compared with participants on day shifts, after adjustment for gender, age and marital status. Principal components analysis and ordinal logistic regression were used am…

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Altered circadian rhythm, sleep, and rhodopsin 7-dependent shade preference during diapause in Drosophila melanogaster.

To survive adverse environments, many animals enter a dormant state such as hibernation, dauer, or diapause. Various Drosophila species undergo adult reproductive diapause in response to cool temperatures and/or short day-length. While flies are less active during diapause, it is unclear how adverse environmental conditions affect circadian rhythms and sleep. Here we show that in diapause-inducing cool temperatures, Drosophila melanogaster exhibit altered circadian activity profiles, including severely reduced morning activity and an advanced evening activity peak. Consequently, the flies have a single activity peak at a time similar to when nondiapausing flies take a siesta. Temperatures ≤15 °C, rather than photoperiod, primarily drive this behavior. At cool temperatures, flies rapidly enter a deep-sleep state that lacks the sleep cycles of flies at higher temperatures and require high …

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Melatonin as a Potential Adjuvant Treatment for COVID-19 beyond Sleep Disorders.

Melatonin is registered to treat circadian rhythm sleep-wake disorders and insomnia in patients aged 55 years and over. The essential role of the circadian sleep rhythm in the deterioration of sleep quality during COVID-19 confinement and the lack of an adverse effect of melatonin on respiratory drive indicate that melatonin has the potential to be a recommended treatment for sleep disturbances related to COVID-19. This review article describes the effects of melatonin additional to its sleep-related effects, which make this drug an attractive therapeutic option for treating patients with COVID-19. The preclinical data suggest that melatonin may inhibit COVID-19 progression. It may lower the risk of the entrance of the SARS-CoV-2 virus into cells, reduce uncontrolled hyper-inflammation and the activation of immune cells, limit the damage of tissues and multiorgan failure due to the actio…

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Melatonin: an endogenous miraculous indolamine, fights against cancer progression.

Purpose: Melatonin is an amphipathic indolamine molecule ubiquitously present in all organisms ranging from cyanobacteria to humans. The pineal gland is the site of melatonin synthesis and secretion under the influence of the retinohypothalamic tract. Some extrapineal tissues (skin, lens, gastrointestinal tract, testis, ovary, lymphocytes, and astrocytes) also enable to produce melatonin. Physiologically, melatonin regulates various functions like circadian rhythm, sleep-wake cycle, gonadal activity, redox homeostasis, neuroprotection, immune-modulation, and anticancer effects in the body. Inappropriate melatonin secretion advances the aging process, tumorigenesis, visceral adiposity, etc. METHODS: For the preparation of this review, I had reviewed the literature on the multidimensional activities of melatonin from the NCBI website database PubMed, Springer Nature, Science Direct (Elsevi…

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Melatonin and Synthetic Melatoninergic Agonists in Psychiatric and Age-associated Disorders: Successful and Unsuccessful Approaches.

Melatonin and the following approved or investigational synthetic melatoninergic agonists are compared with regard to half-life, receptor affinity, metabolism and additional properties: TIK-301, piromelatine, GG-012, AH-001, AH-017, agomelatine, ramelteon, GR 196429, MA-2, tasimelteon, UCM765, and UCM924. Apart from restrictions from the respective approvals, theoretical limits of treatment are outlined as they result from chronobiological, genetic, epigenetic, degenerative or toxicological considerations. Melatoninergic agonists have been shown to reliably entrain circadian rhythms, if chronobiological phase response rules are followed. This allows the treatment of dysphased rhythms, circadian rhythm sleep disorders, and forms of depression with an etiology of circadian dysfunction, such as bipolar disorder and seasonal affective disorders. Entrainment and induction of sleep onset requi…

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Melatonin effects on bone: potential use for the prevention and treatment for osteopenia, osteoporosis, and periodontal disease and for use in bone-grafting procedures.

An important role for melatonin in bone formation and restructuring has emerged, and studies demonstrate the multiple mechanisms for these beneficial actions. Statistical analysis shows that even with existing osteoporotic therapies, bone-related disease, and mortality are on the rise, creating a huge financial burden for societies worldwide. These findings suggest that novel alternatives need to be developed to either prevent or reverse bone loss to combat osteoporosis-related fractures. The focus of this review describes melatonin's role in bone physiology and discusses how disruption of melatonin rhythms by light exposure at night, shift work, and disease can adversely impact on bone. The signal transduction mechanisms underlying osteoblast and osteoclast differentiation and coupling with one another are discussed with a focus on how melatonin, through the regulation of RANKL and oste…

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Melatonin treatment for insomnia in pediatric patients with attention-deficit/hyperactivity disorder.

Objective: To evaluate the efficacy and safety of melatonin for the treatment of insomnia in pediatric patients with attention-deficit/hyperactivity disorder (ADHD). Data sources: Literature was accessed through MEDLINE (1948-August 2009), EMBASE (1950-August 2009), and Scopus (1960-August 2009) using the terms melatonin, attention-deficit/hyperactivity disorder (ADHD), pediatric, insomnia, sleep disorder, and sleep. In addition, reference citations from publications identified were reviewed for relevant information. Study selection and data extraction: All English-language articles and human studies were identified and evaluated. Results from all identified randomized trials (n = 5), safety studies (n = 1), long-term follow-up studies (n = 1), post hoc retrospective analyses (n = 1), meta-analyses (n = 2), review articles (n = 9), and letters (n = 1) were summarized. Data synthesis: Ped…

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Melatonergic drugs in clinical practice.

Melatonin (CAS 73-31-4) has both hypnotic and sleep/wake rhythm regulating properties. These sleep promoting actions, which are already demonstrable in healthy humans, have been found useful in subjects suffering from circadian rhythm sleep disorders (CRSD) like delayed sleep phase syndrome (DSPS), jet lag and shift-work sleep disorder. Low nocturnal melatonin production and secretion have been documented in elderly insomniacs, and exogenous melatonin has been shown to be beneficial in treating sleep disturbances of these patients. In comparison to a number of sleep-promoting compounds that are usually prescribed, such as benzodiazepines and z-drugs (zolpidem and zopiclon belonging to the latter ones), melatonin has several advantages of clinical value: it does not cause hangover nor withdrawal effects and is devoid of any addictive potential. However, recent meta-analyses revealed that …

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Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways.

Melatonin, an endogenous signal of darkness, is an important component of the body's internal time-keeping system. As such it regulates major physiological processes including the sleep wake cycle, pubertal development and seasonal adaptation. In addition to its relevant antioxidant activity, melatonin exerts many of its physiological actions by interacting with membrane MT1 and MT2 receptors and intracellular proteins such as quinone reductase 2, calmodulin, calreticulin and tubulin. Here we review the current knowledge about the properties and signaling of melatonin receptors as well as their potential role in health and some diseases. Melatonin MT1 and MT2 receptors are G protein coupled receptors which are expressed in various parts of the CNS (suprachiasmatic nuclei, hippocampus, cerebellar cortex, prefrontal cortex, basal ganglia, substantia nigra, ventral tegmental area, nucleus a…

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Role of the melatonin system in the control of sleep: therapeutic implications.

The circadian rhythm of pineal melatonin secretion, which is controlled by the suprachiasmatic nucleus (SCN), is reflective of mechanisms that are involved in the control of the sleep/wake cycle. Melatonin can influence sleep-promoting and sleep/wake rhythm-regulating actions through the specific activation of MT(1) (melatonin 1a) and MT(2) (melatonin 1b) receptors, the two major melatonin receptor subtypes found in mammals. Both receptors are highly concentrated in the SCN. In diurnal animals, exogenous melatonin induces sleep over a wide range of doses. In healthy humans, melatonin also induces sleep, although its maximum hypnotic effectiveness, as shown by studies of the timing of dose administration, is influenced by the circadian phase. In both young and elderly individuals with primary insomnia, nocturnal plasma melatonin levels tend to be lower than those in healthy controls. Ther…

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Melatonin: Nature's most versatile biological signal?

Melatonin is a ubiquitous molecule and widely distributed in nature, with functional activity occurring in unicellular organisms, plants, fungi and animals. In most vertebrates, including humans, melatonin is synthesized primarily in the pineal gland and is regulated by the environmental light/dark cycle via the suprachiasmatic nucleus. Pinealocytes function as 'neuroendocrine transducers' to secrete melatonin during the dark phase of the light/dark cycle and, consequently, melatonin is often called the 'hormone of darkness'. Melatonin is principally secreted at night and is centrally involved in sleep regulation, as well as in a number of other cyclical bodily activities. Melatonin is exclusively involved in signaling the 'time of day' and 'time of year' (hence considered to help both clock and calendar functions) to all tissues and is thus considered to be the body's chronological pace…

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Therapeutic potential of melatonin ligands.

Melatonin is a neurohormone that is believed to be involved in a wide range of physiological functions. In humans, appropriate clinical trials confirm the efficacy of melatonin or melatoninergic agonists for the MT1 and MT2 receptor subtypes in circadian rhythm sleep disorders only. Nevertheless, preclinical animal model studies relevant to human pathologies involving validated reference compounds lead to other therapeutic possibilities. Among these is a recently developed treatment concept for depression, which has been validated by the clinical efficacy of agomelatine, an agent having both MT1 and MT2 agonist and 5-HT2C antagonist activity. A third melatonin binding site has been purified and characterized as the enzyme quinone reductase 2 (QR2). The physiological role of this enzyme is not yet known. Recent results obtained by different groups suggest: (1) that inhibition of QR2 may l…

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