What is the mechanism responsible for the periodicity of hiccups?

What is the mechanism responsible for the periodicity of hiccups?

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Hiccups (singultus) are caused by involuntary spasm of the intercostal muscles and diaphragm, producing a sudden inspiration with associated glottic closure. It seems the neurobiology of the reflex has been relatively well worked out (nicely summarized in this review):

  • Afferent limb: the vagus, phrenic, and cervical sympathetic chain
  • Central mediators: the hypothalamus, medullary reticular formation, and brainstem respiratory centers
  • Efferent limb: primarily mediated by the phrenic nerve but also including the intercostals, and secondarily the recurrent laryngeal nerve to cause glottic closure

To my knowledge, hiccups are always cyclical, with a period of between 1 and 30 seconds. According to the afore cited article, this interval is relatively constant it a given individual. The cycling stops after some time; efferent vagal tone can suppress it, or it stops spontaneously. My question is:

  • What is the mechanism responsible for this periodicity?

Something must be triggering that afferent limb every 1 - 30s, but I can't think of a normal physiologic process that triggers the firing of one or more nerves with such periodicity and then stops abruptly.

Check out Van Der Pol (chaotic) oscillator. It can be used to model heart rhythms. If a stimulus is applied to the oscillator, it will return to the curved envelope discussed in the article.

However, if "pushed just right", the oscillator's current state will be pushed towards the very center of the loop, and it will stop oscillating. This is the mechanism by which a sudden blow to the chest can stop the heart.

Reading up on hiccups, their "almost regular" interval sounds similar to a chaotic oscillator. The abrupt stop may represent pushing the oscillator towards the middle of the limit cycle, from which it cannot recover, effectively stopping hiccups

Briefly describe the cellular events responsible for the refractory period (hint: discuss the mechanism of repolarization).

Briefly describe the cellular events responsible for the refractory period (hint: discuss the mechanism of repolarization):

The buildup of potassium during repolarization into hyperpolarization, that makes it more difficult for the stimulus to reach its threshold, is the events responsible for the refractory period. It is measured for the earthworm as the largest interval wherein the action potential (second spike) cannot be generated.

correct answer is option a.

tropopause, stratopause and mesopause have all in common aspect that is point of maximum temperature in its layer of the atmosphere. all layers of atmosphere observe abrupt change in temperature. tropopause is the boundary between troposphere and stratosphere. stratopause is the boundary between stratosphere and mesosphere. mesopause is the boundary between mesosphere and thermosphere. these all boundaries are ranges between altitude of 0 to 80 km.

The 24-hour periodicity of microfilariae: biological mechanisms responsible for its production and control

An explanation is presented which covers most of the experimental data about the mechanisms by which the periodicity of microfilariae is maintained: During the night-time (with Wuchereria bancrofti and similar filariae) the microfilariae are evenly distributed throughout the blood and they are thus available for ingestion and transmission by mosquitoes. During the day-time they accumulate in the small vessels of the lungs, and hence they are few in the peripheral blood this phase is probably adapted to allow the microfilariae to enjoy favourable physiological conditions in the lungs. The accumulation is due to an active reflex by the microfilariae themselves and it probably depends on a sideways migration through the precapillary network of arterioles. The factor in the lungs which holds up the passage of the microfilariae so that they accumulate there (in preference to the capillaries of other organs), is the great increase in oxygen tension, which may be termed the ‘oxygen barrier’. The 24 h cycle of the microfilariae is orientated to the 24 h cycle of the host and some rhythmic change in the host acts as a cue to the microfilariae. Each microfilaria has a weak endogenous circadian rhythm of its own, but the rhythms of the individual microfilariae are dominated by that of the host, so that all the different individuals do approximately the same thing at the same time, and they do it at the right time (i.e. right for transmission). Different species of microfilariae respond differently to the same stimuli, and they depend on different arrangements for the maintenance of their rhythms. Three main groups of periodic microfilariae may be recognized. (а) W. bancrofti, Brugia malayi, etc. These depend upon the absolute size of the venousarterial (VA) difference in oxygen tension (‘oxygen barrier’) which is lower by night (e.g. 40 mmHg) than it is by day (e.g. 55 mmHg) and so the microfilariae pass through the lungs by night but accumulate there by day. If at night the patient is caused to breathe oxygen, the arterial oxygen rises or if he is caused to take vigorous muscular exercise, the venous oxygen tension falls in both cases the VA difference becomes greater and the microfilariae accumulate in the lungs. (b) Loa loa of man, Edesonfilaria malayensis of monkeys in Thailand and Monnigofilaria setariosa of East African mongooses. In this group the sensitivity of the microfilariae to the oxygen barrier is greatly increased or decreased by the 24 h changes in the body temperature of the host. Accordingly, the cycle of microfilariae of this group indirectly depends upon the temperature cycle of the host. (c) Dirofilaria immitis, D. repens of dogs, D. aethiops (corynodes) of monkeys, etc. These microfilariae are probably sensitive only to the lower range of oxygen tensions, e.g. 30 to 60 mmHg. On the whole their cycle depends on day-night changes in the oxygen barrier as with W. bancrofti, but under special circumstances (as explained in the text) administration of oxygen may cause liberation of microfilariae from the lung instead of accumulation. The mechanism controlling the Pacific type of W. bancrofti cannot yet be identified, since the experimental evidence is insufficient. The behaviour of microfilariae is adapted to promote transmission by arranging the maximum number of microfilariae in the peripheral blood at times when the arthropod vector is likely to bite. The most sophisticated arrangement to achieve this is by a 24 h rhythm—the classical ‘periodicity’. A less sophisticated arrangement is illustrated by various filariae of rodents, e.g. Litomosoides carinii and Dipetalonema witei, in which the parasites are transmitted by mites or ticks which suck blood in the nest or burrow, and the microfilariae are stimulated to swarm in the peripheral blood by a fall in body temperature when the animal sits quietly in its nest. Filariae which are still less sophisticated, e.g. Acanthocheilonema perstans and Dipetalonema gracile, do not possess any arrangements for adjusting the supply of microfilariae in the peripheral blood to the feeding habits of the vectors. Furthermore, some microfilariae, e.g. those of D. immitis and D. repens, are adjusted to their vectors on an annual variation as well as on a 24 h one and they are most numerous in the blood during July and August (when mosquitoes are most numerous in temperate zones). Some hosts (e.g. dogs) have a less marked 24 h rhythm than other hosts (e.g. man and monkey) and the cycles of their microfilariae are similarly less marked.


Loiasis is caused by the nematodes (roundworm) Loa loa that can inhabit the lymphatics and subcutaneous tissues of humans.

Life Cycle:

The vector for Loa loa filariasis are flies from two species of the genus Chrysops, C. silacea and C. dimidiata. During a blood meal, an infected fly (genus Chrysops, day-biting flies) introduces third-stage filarial larvae onto the skin of the human host, where they penetrate into the bite wound . The larvae develop into adults that commonly reside in subcutaneous tissue . The female worms measure 40 to 70 mm in length and 0.5 mm in diameter, while the males measure 30 to 34 mm in length and 0.35 to 0.43 mm in diameter. Adults produce microfilariae measuring 250 to 300 &mum by 6 to 8 &mum, which are sheathed and have diurnal periodicity. Microfilariae have been recovered from spinal fluids, urine, and sputum. During the day they are found in peripheral blood, but during the noncirculation phase, they are found in the lungs . The fly ingests microfilariae during a blood meal . After ingestion, the microfilariae lose their sheaths and migrate from the fly&rsquos midgut through the hemocoel to the thoracic muscles of the arthropod . There the microfilariae develop into first-stage larvae and subsequently into third-stage infective larvae . The third-stage infective larvae migrate to the fly&rsquos proboscis and can infect another human when the fly takes a blood meal .

Mechanism of Fever

A) Based on Duration of Fever:

  1. Acute fevers (<7 days): infectious diseases such as malaria and viral-related upper respiratory tract infection
  2. Sub-acute fevers (usually not more than 2 weeks in duration): typhoid fever and intra-abdominal abscess
  3. Chronic or persistent fevers (>2 weeks duration): chronic bacterial infections such as tuberculosis, viral infections like HIV, cancers and connective tissue diseases. However, any cause of acute fever can become persistent or chronic if untreated.

B) Based on Height of Fever:

Normal and febrile body temperature ranges (rectal temperatures).

Body temperature°C°F
Mild/low grade fever38.1–39100.5–102.2
Moderate grade fever39.1–40102.2–104.0
High grade fever40.1–41.1104.1–106.0
Hyperpyrexia a >41.1>106.0

C) Based on Pattern of Fever:

1. Sustained or Continuous Fever: Fever that oscillates less than 1 ºC or

1.5 ºF daily doesn’t touch normal

2. Remittent Fever: Fever that oscillates more than 1 ºC or

1.5 ºF doesn’t touch normal

3. Intermittent Fever: Fever that falls to normal each day.

  • Quotidian (24 hour periodicity): P. falciparum
  • Double quotidian (12 hour periodicity): Kala-azar, Gonococcal arthritis, Juvenile RA, Some drug fevers (carbamazepine)

4. Hectic or Septic Fever: When remittent or intermittent fever shows large variation between the peak and nadir

5. Periodic or Cyclic Fever: Episodes of fever recurring at regular intervals

  • Tertian (48 hour periodicity): P. vivax, P. ovale
  • Quartan (72 hour periodicity): P. malariae
  • Pel-Ebstein Fever: bouts of fever lasting 3 to 10 days followed by asymptomatic periods of the same length (Hodgkin’s disease)
  • Relpasing fever (every 10-14 days): Borrelia recurrentis
  • Undulant fever (gradual increase in temperature that remains high for a few days, and then gradually decreases to normal): Brucellosis

6. Recurrent Fever: Illness involving the same organ (e.g. urinary tract) or multiple organ systems in which fever recurs at irregular interval

Dark chocolate (70% organic cacao) increases acute and chronic EEG power spectral density (μV 2 ) response of gamma frequency (25–40 Hz) for brain health: enhancement of neuroplasticity, neural synchrony, cognitive processing, learning, memory, recall, and mindfulness meditation

Cacao or dark chocolate is a major source of flavonoids. Flavonoids are extremely potent antioxidants and anti-inflammatory agents, with known mechanisms beneficial for cardiovascular health. However, the correlates of neuroelectric activity that initiate the mechanisms of cacao's effects on brain neurocognition, synchronization, memory, recall, mood and behavior are not well known. Studies have shown that absorbed cacao flavonoids penetrate and accumulate in brain hippocampal regions involved in learning and memory. However, neurological initiation and modulatory control from acute and chronic exposure of cacao flavanoids (via consumption) on intensity of kinetic response of brain frequency and specifically beneficial gamma frequency (25–40 Hz), has not been studied.


Therefore, the purpose of this study was to assess the Electroencephalography (EEG) response to consuming 48 g of dark chocolate (70% cacao) after an acute period of time (30 mins) and after a chronic period of time (120 mins), on modulating brain frequencies 0–40 Hz specifically beneficial gamma frequency (25–40 Hz).


Dark chocolate bars, made from Tanzania organic cocoa beans consisting 70% cacao and 30% organic cane sugar, were used in this study (Parliament Chocolate, Redlands, CA). EEG wave bandwidth activity was recorded from 9 cerebral cortical scalp locations F3, Fz, F4, C3, Cz, C4, P3, Pz, and P4 using the EEG B-Alert 10X System™ (Advanced Brain Monitoring, Carlsbad, CA). Each of 5 healthy subjects, age 22–40, consumed 48 g of the dark chocolate after the baseline EEG acquisition. At an acute period of time (30 mins) and chronic period of time (120 mins) EEG was recorded for two mins. From each of the 5 subjects and summated for the respective time points. Power Spectral Density uV 2 (PSD) were Z-scored for the two time points using the reference pretest resting EEG baseline..


Z-scores were graphed for both acute and chronic time periods across 0–40 Hz (Fig. 1). The most significant outcome observed showed PSD γBA was quantitatively greatest of all frequencies in the study (p<0.01). In Fig, 2, using “heatmaps”, we show qualitative responses for extent and intensity (PSD) of the cacao on the cerebral cortical brain for: baseline (Task 1 – after 8 hr n.p.o., and no cacao) for both acute and chronic time periods (Task 2 – 30 mins post consumption and Task 3 – 120 mins post consumption, respectively). The acute time period (Task 2) clearly shows the entire cerebral cortical region is modulated to varying degrees of PSD increase in γBA, with the largest increase in regions C4/P4/PZ/P3, while the chronic time period (Task 3) shows the frontal left side returning towards baseline, but still has residual γBA in C4/P4/Pz regions.


This study provides quantitative and qualitative evidence that EEG γBA is enhanced by consumption of 48 g 70% cacao and shows a significant acute effect at 30 mins post consumption to all cerebral cortical regions, and a residual γBA PSD response at 120 mins., primarily to brain EEG regions C4/P4/Pz. We suggest that 48 g 70% cacao consumption with a concentration of antioxidant activity of 52,000 umoles TE/100 g, is associated with subsequent γBA increase in the cerebral cortical brain. We suggest that this superfood of 70% cacao (organic cocoa beans from Tanzannia) enhances neuroplasticity for behavioral and brain health benefits. Further research is in progress to elaborate the mechanisms that may be involved in the cause/effect brain-behavior relationship.

Support or Funding Information

Departmental, School of allied Health Professions, Loma Linda University

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

National Cancer Institute (NCI)

The Division of Cancer Biology (DCB) at the National Cancer Institute (NCI) announces the opportunity for current Physical Sciences-Oncology Network (PS-ON), Cancer Tissue Engineering Collaborative (TEC), Cancer Systems Biology Consortium (CSBC), and Patient-Derived Models of Cancer (PDMC) awardees to apply for supplemental funding to support collaborative research projects. Collaborations can include investigators within one consortium, across consortia, or may include investigators who are not currently supported by the DCB research programs listed above. Collaborative projects must include at least one investigator not named as key personnel on the parent award. The proposed research plan must be within the overall scope of the active parent U54, U01, R37 and/or R01 award. All potential applicants are highly encouraged to contact their NCI Program Director to discuss the planned collaboration and application.

Application and Submission Information

Applications for this initiative must be submitted using the following opportunity or its subsequent reissued equivalent:

PA-20-272 - Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional).

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

Requests for support of clinical trials will not be accepted and/or considered in response to this funding opportunity announcement.

All supplement requests must be submitted electronically through eRA Commons, see NOT-OD-20-128 for more information.

Applicants are strongly encouraged to notify the NCI Program Director assigned to the parent award that a request has been submitted in response to this NOSI in order to facilitate efficient processing of the request.

Eligibility and Eligible Individuals (Program Director/Principal Investigator):

  • Awardees/Applicant(s) must hold an active grant or cooperative agreement in the PS-ON, TEC, CSBC, or PDMC programs, as awarded under the funding opportunity announcements (FOAs) listed below:
  • To be eligible, the parent award must be able to receive funds in FY21 and be active throughout the 1-year project period. The parent award must not be in an extension period (e.g., cost or no-cost extension).
  • For supplements to parent awards that include multiple program directors/principal investigators (PD/PIs), the supplement may be requested by any or all of the PD/PIs (in accordance with the existing leadership plan) and submitted by the awardee institution of the parent award.
  • Up to two administrative supplement applications may be submitted by each parent award. If more than two applications are submitted from a given parent award all applications will be administratively withdrawn from consideration.
  • Early Stage Investigators (ESIs) are encouraged to apply.
  • Collaborations with foreign institutions are allowed, but investigators must provide a justification for the collaboration. Please note that some foreign collaborations will require U.S. State Department approval by the NCI, and that may delay receipt of funding.

Application Due Date:

  • All requests, regardless of parent award funding mechanism, must be received by 5:00 PM local time on April 16, 2021.
  • This is a one-time announcement. Late applications will not be accepted.
  • Supplement budget request must reflect the actual needs of the proposed one-year project.
  • At least one full year on the parent grant must remain at the time of funding. The application budget is limited to one year only.
  • The earliest anticipated start date is August 1, 2021.
  • Requests for no-cost extensions on the parent grant to accommodate a supplement will not be permitted.
  • If the budget includes a request for salary support, it is required to include a justification and clear details on what each person will be responsible for.
  • If supporting students and/or postdoctoral fellows, please indicate if they are already working in the lab or when they will be recruited. A description of how the student/postdoctoral fellow will be supported after the conclusion of the one-year supplement must be included.
  • It is not appropriate to have to be named (TBN) personnel listed as part of the budget request.
  • Including support for a patient advocate to partner on a supplemental project is acceptable.
  • The administrative supplement awards pursuant to this opportunity are contingent upon the availability of funds from NCI and the receipt of a sufficient number of meritorious requests.

Submitting Applications:

  • Applicants should begin the supplement application abstract by stating “This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA-21-030.”
  • For funding consideration, applicants must include “NOT-CA-21-030” (without quotation marks) in the Agency Routing Identifier field (box 4b) of the SF424 R&R form. Applications without this information in box 4b will not be considered for this initiative.
  • Page limits: The Research Strategy section of the application is limited to 3 pages (excluding references). If previous PS-ON, TEC, CSBC, or PDMC collaborative administrative supplements were obtained by the applicant, an additional 1-page is allowed to outline the results of previous awards.

Review and Selection Process:

NCI will conduct administrative reviews of applications and will support the most meritorious applications submitted for consideration, based upon the availability of funds.

Specific Review Criteria

NIH staff will consider the ability of the proposed supplement activities to increase the parent award’s overall impact within the original scope of the award. Other criteria that will be considered during the review include:

  • The significance of the specific question being pursued
  • The requirement for collaborative research to accomplish the goals of the project
  • A rigorous study or experimental design with adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects
  • The applicability of the approach to requirements from the FOA to which the parent application was submitted (e.g., Does the approach include physical sciences and engineering, iterative systems biology, or patient-derived or tissue-engineered model systems?)
  • A realistic scope of work, given the time and budget requested
  • The successful completion of previous administrative supplement projects, if applicable.

Applications nonresponsive to terms of this NOSI will be not be considered for the NOSI initiative.

Applicants are encouraged to discuss their application with the scientific/research contact listed in this NOSI prior to submission.

What Causes Climate Change?

A simplified animation of the greenhouse effect. Credit: NASA/JPL-Caltech

There are lots of factors that contribute to Earth’s climate. However, scientists agree that Earth has been getting warmer in the past 50 to 100 years due to human activities.

Certain gases in Earth’s atmosphere block heat from escaping. This is called the greenhouse effect. These gases keep Earth warm like the glass in a greenhouse keeps plants warm.

Human activities — such as burning fuel to power factories, cars and buses — are changing the natural greenhouse. These changes cause the atmosphere to trap more heat than it used to, leading to a warmer Earth.

Altered Neuromuscular Control Theory

Instead, researchers are now considering the possibility that cramps are a phenomenon associated with &ldquoaltered neuromuscular control,&rdquo stemming from multiple factors including muscle fatigue and damage.

This would explain why the muscles affected by cramp are usually those that have been working hardest.

This theory posits that your muscles are always held in a delicate balance between two types of reflex: one that encourages them to contract and one that encourages them to relax. But exercise can upset this balance and cause a cramp.


Plants also use the phytochrome system to adjust growth according to the seasons. Photoperiodism is a biological response to the timing and duration of dark and light periods. Since unfiltered sunlight is rich in red light, but deficient in far-red light, at dawn, all the phytochrome molecules in a leaf convert to the active Pfr form and remain in that form until sunset. Since Pfr reverts to Pr during darkness, there will be no Pfr remaining at sunrise if the night is long (winter) and some Pfr remaining if the night is short (summer). The amount of Pfr present stimulates flowering, setting of winter buds, and vegetative growth according to the seasons.

In addition, the phytochrome system enables plants to compare the length of dark periods over several days. Shortening nights indicate springtime to the plant lengthening nights indicate autumn. This information, along with sensing temperature and water availability, allows plants to determine the time of the year and adjust their physiology accordingly. Short-day (long-night) plants use this information to flower in the late summer and early fall when nights exceed a critical length (often eight or fewer hours). Long-day (short-night) plants flower during the spring when darkness is less than a critical length (often 8 to 15 hours). However, day-neutral plants do not regulate flowering by day length. Not all plants use the phyotochrome system to adjust their physiological responses to the seasons.

Watch the video: loco παξιμάδια. μεταδοτική λόξυγκας. βίντεο διασκέδασης. Loco Nuts Show. Contagious Hiccups (September 2022).


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