2646
Views & Citations1646
Likes & Shares
High-altitude pulmonary edema (HAPE) occurs in unacclimatized
individuals who are rapidly exposed to altitude in excess of 2500 m above sea
level. A working hypothesis of the etiology of HAPE suggests that hypoxic
pulmonary vasoconstriction is extensive and precapillary resistance is
elevated. The result is dilatation of the capillaries and capillary injury,
with leakage of protein and red cells into the alveoli and airways. However,
the question remains: why HAPE develops only in some individuals, who are
rapidly exposed to high-altitudes? Our experience in studying the genetics of
human adaptation to high-altitude shows that the hereditary factor may plays a
role. Based on study of chromosomal heterochromatic regions (HRs) the
hypothesis of thermoregulation at the cell level has been advanced. The
essence of the cell thermoregulation is elimination of
the temperature difference
between the nucleus
and cytoplasm. It has been shown
that the amount of HRs influence on the level of the human body heat
conductivity. The amount of chromosomal
HRs is subject to wide variability in human population. When individuals with a high amount of HRs
happened to be in cool high-altitude condition their bodies are rapidly and
deeply cooled due to their high body heat conductivity with all the ensuing
consequences. Therefore, it is possible that under all other conditions being
equal, HAPE most often develops in individuals with a large amount of
chromosomal HRs in the genome.
Keywords: High-Altitude
Pulmonary Edema, Q-Heterochromatin, Condensed Chromatin, Human Body Heat
Conductivity, Human Adaptation
INTRODUCTION
High-altitude pulmonary edema (HAPE) occurs
in unacclimatized individuals who are rapidly exposed to altitude in excess of
2450 m. It is commonly seen in climbers and skiers who ascend to high altitude
without previous acclimatization. Initial symptoms of dyspnea, cough, weakness,
and chest tightness appear, usually within 1-3 days after arrival. Common
physical signs are tachypnea, tachycardia, rales, and cyanosis. Descent to a
lower altitude, nifedipine, and oxygen administration result in rapid clinical
improvement. HAPE represents one of the few varieties of pulmonary edema where
left ventricular filling pressure is normal (Hultgren, 1996).
The majority of persons who ascend rapidly
to terrestrial elevation higher than approximately 2500 m undergo an unpleasant
period of acclimatization. During this time, they have a variety of symptoms,
the most prominent of which are headache, nausea, vomiting, and insomnia that
are collectively referred to as acute mountain sickness (Hall et al., 1965;
Singh et al., 1969; Hackett, 1980). Acute mountain sickness is part of a
continuum of diseases related to ascension to high altitudes (Houston, 1976)
that includes the infrequent life-threatening conditions high-altitude
pulmonary edema (Schoene, 1985) and cerebral edema (Hamilton et al., 1986).
The pathophysiological mechanisms of HAPE
have been studied fairly well.
Physiologic studies during the acute stage have revealed a normal
pulmonary artery wedge pressure, marked elevation of pulmonary artery pressure,
severe arterial unsaturation, and usually a low cardiac output. Pulmonary
arteriolar (precapillary) resistance is elevated. A working hypothesis of the
etiology of HAPE suggests that hypoxic pulmonary vasoconstriction is extensive
but not uniform. The result is over perfusion of the remaining patent vessels with
transmission of the high pulmonary artery pressure to capillaries. Dilatation
of the capillaries and high flow results in capillary injury, with leakage of
protein and red cells into the alveoli and airways (Hultgren, 1996).
However, the question remains: why HAPE
develops only in some individuals, who are rapidly exposed to altitudes in
excess of 2500 m above sea level? For example, HAPE was originally thought to
be rare in women, but subsequent studies have shown that women do develop HAPE,
albeit at a lower incidence than men. A review of 229 cases of HAPE revealed a
male preponderance of 87% (Lobenhoffer et al., 1982; Sophocles, 1986;
Hochstrasser et al., 1986; Hultgren et al., 1996). Although HAPE is more
frequent in males, no sex difference has been noted in acute mountain sickness
(Hackett et al., 1976). Children are more susceptible to HAPE than adults. A
study made in Peru of 1157 ascents from see level to 3782 m reported that
individuals aged 13-20 years had the highest incidence of HAPE (17%), whereas
adults age 21 or older had an incidence of only 3% (Hultgren and Marticorena,
1978). Our long-term experience in
studying the genetic basis of human adaptation to some extreme climatic and
geographic conditions, including the high mountains of the Pamir and the Tien
Shan, shows that the hereditary factor may plays a role in the development of
HAPE.
METHODS AND RESULTS
Sample Characteristics
During the last 50
years, scientists of our Center have systematically studied the physiology,
pathology and genetics of the inhabitants of the highland areas of the Pamir
and Tien Shan. During these years we managed to observe only one case of HAPE
that occurred with one of our colleagues in the Eastern Pamir in the village of
Murgab located at an altitude of 3600 m above sea level (asl). We left by car
from the city of Osh (160 m asl) and reached the village in two days, driving
through, among other things, the three highest mountain passes (from 3,615 to
4,655 m asl) of the Pamirs. The trip itself was carried out by the members of
the scientific expedition relatively well and placed in a local hotel. However,
at midnight, the condition of one of the expedition members (male, 24 years
old, physically healthy) began to deteriorate sharply. Expedition doctors
diagnosed HAPE, conducted all necessary medical interventions and the next day
in the morning they flown down to Osh city for further observation. Everything
ended well, after the landing in the airport he felt normal and soon he went to
see the sights of the city.
Cytogenetic Methods
Chromosomal
preparations were made using short-term cultures of peripheral blood
lymphocytes, with the exception of newborn infants where umbilical blood was
used. The cell cultures were processed according to slightly modified
(Ibraimov, 1983) conventional methods (Hungerford, 1965). The dye used was
quinacrine mustard. All the chromosomal preparations were analyzed by one and
the same cytogeneticist (A.I.I.) to investigate chromosomal Q-HR variability.
Calculation and registration of chromosomal Q-HRs was performed using the
criteria and methods described in detail elsewhere (Ibraimov et al., 1982,
1990).
Quantitative Characteristics of chromosomal
Q-HR Variability
Q-HR variability of
autosomes in populations is usually described in the form of three main
quantitative characteristics: 1) The distribution of the number of Q-HRs in a
population, i.e., distribution of individuals having different numbers of Q-HRs
in the karyotype regardless of their location on seven Q-polymorphic autosomes,
which also reflected the range of Q-HRs variability in the population
genome; 2) The derivative of this
distribution, an important population characteristic, is the mean number of
Q-HRs per individual; 3) The frequency of Q-HRs on seven Q-polymorphic
autosomes (3, 4, 13-15, 21 and 22) in the population. Despite the fact that in
human autosomes there are twelve loci in which Q-HRs can be detected (3 cen, 4
cen, 13 p11, 13 p13, 14 p11, 14 p13, 15 p11, 15 p13, 21 p11, 21 p13, 22 p11, 22
p13), individuals with 24 Q-HRs in their genome could exist, but such cases have not as yet been
reported. In individuals of a population the number of Q-HRs on the autosomes
usually ranges from zero to ten (Yamada & Hasegawa, 1978; Al-Nassar et al.,
1981; Ibraimov & Mirrakhimov, 1985).
Results and Discussion
After returning to
the Center, in all members of the expedition examined their karyotype,
including the polymorphism of chromosomal Q-HRs. It turned out that they are
not different from normal individuals in terms of the location, number, size
and intensity of fluorescence of chromosomal Q-HRs. The only difference was in
the individual who endured HAPE: he has a large amount of chromosomal Q-HRs in
his karyotype. As can be seen from Fig. 1 in this individual on three autosomes
(3, 13 and 21) and on the Y chromosome, there are seven chromosomal Q-HRs
different sizes and fluorescent intensities.
The fact is that in Kyrgyzstan, the number of
chromosomal Q-HRs in individuals in the population ranges from 0 to 7,
averaging 2.8 (Ibraimov et al., 1982; 1986). But in order to clarify our
position on the possible role of heredity in the pathogenesis of HAPE, it is
necessary to have some idea of the nature of chromosomal polymorphism, based
on variability, the so-called heterochromatic regions of chromosomes.
To-date two types of heterochromatin are
recognized: Q- and C-heterochromatin (Caspersson et al., 1970; Arrighi &
Hsu, 1971; Paris Conference, 1971;
Suppl., 1975). Despite the fact that chromosomal C- and
Q-heterochromatin are defined by a single term, “constitutive heterochromatin”,
they are undoubtedly significantly different intrachromosomal structures
(Prokofyeva-Belgovskaya, 1986).
There are several significant differences between them:
C-heterochromatin is found in
the chromosomes of all
the higher eukaryotes,
while Q-heterochromatin - only in man
(Homo sapiens), the chimpanzee (Pan troglodytes) and
gorilla (Gorilla gorilla) (Pearson,
1973, 1977). C-heterochromatin regions
(C-HRs) are known to be invariably present in all the
chromosomes of man, varying mainly in size
and location (inversion). However, chromosomal Q-HRs is subject to
considerably greater variability in human populations as compared to C-HRs
(Erdtmann, 1982).
Regarding the distribution pattern of
chromosomal Q-HRs at the population level the following reliable data obtained:
1) Q-HRs are found on certain loci of only seven autosomes in both sexes, as
well as on the Y chromosome in males; 2) despite the fact that in the human
karyotype there are 25 loci where chromosomal Q-HRs could potentially be found,
in reality the maximal number of Q-HRs does not exceed 10; 3) in human
populations the number of Q-HRs in the karyotype usually ranges from 0 to 10;
4) the amount of Q-HRs in the population genome is best determined by the value
of the mean number of Q-HRs per individual (); 5) there are significant interpopulation
differences in the quantitative content of chromosomal Q-HRs in the population
genome. These differences proved to be related to features of the ecological
environment of the place of permanent residence and not to the racial and
ethnic composition of the populations. Changes in the amount of Q-HRs in the
population genome have a tendency towards a decrease from southern geographical
latitudes to northern ones, and from low-altitude latitudes to high-altitude
ones (Fig. 2); 6) in different age groups values
differ, the greatest number of Q-HRs is characteristic of newborns, while the
least number - in elderly subjects; 7) individuals that are capable to adapt to
the extreme climate of high altitudes (e.g. mountaineers) and to that of the
Far North (e.g. borers - oil industry
workers of the Jamal peninsula, Eastern Siberia) have extremely low numbers of
Q-HRs in their genome (Geraedts and Pearson, 1974; McKenzie and Lubs, 1975;
Buckton et al., 1976; Lubs et al., 1977;
Yamada and Hasegawa, 1978; Al-Nassar et al., 1981; Stanyon et al., 1981; Ibraimov and
Mirrakhimov, 1982a,b,c, 1985; Ibraimov et al., 1982; 1986; 1990; 1991; 2013;
Kalz et al., 2005; Décsey et al., 2006).
Some physiological effects of the amount of
chromosomal HRs in the genome on the human body are also known. Based on study of distribution of chromosomal
HRs in various human populations,
in norm and
at some forms
of pathology the
hypothesis about thermoregulation existence at
the cell level
has been presented.
The essence of
hypothesis of cell
thermoregulation (СТ) is elimination of
the temperature difference
between the nucleus
and cytoplasm when
the nucleus temperature becomes higher than the cytoplasm
temperature (Ibraimov, 2003). The condensed chromatin (СС) localized between a nucleus and cytoplasm is made of different types of
chromosomal HRs. For this reason, СС is
subject to wide variability in population. Obviously, the density of the СС packing depends on the quantity
of chromosomal Q-HRs in
its structure that
can affect upon its heat-conducting ability.
It has been experimentally shown that the
effect of CT can be indirectly assessed by the level of the body heat conductivity
(BHC). In particular, we were able to show that individuals in a population
significantly differ from each other in terms of BHC level. In other words,
there are some parallels in the distribution of the amount of chromosomal Q-HRs
and variability of BHC at the level of human populations (Ibraimov et al.,
2014).
As is known, with HAPE, dilatation of the
capillaries and high flow results in capillary injury, with leakage of protein
and red cells into the alveoli and airways. A working hypothesis of the
etiology of HAPE suggests that hypoxic pulmonary vasoconstriction is extensive
(see above). We believe that the cause of pulmonary vasoconstriction in
addition to hypoxia, perhaps, is the cold inherent in the high-mountain
climate. Since the individuals in the population differ in the level of the
BHC, there is nothing unexpected in the assumption that the HAPE will most
often be exposed to individuals whose bodies are rapidly and deeply cooled due
to their high heat conductivity.
Moreover, in individuals with a high BHC during rapid cooling of the
body in the alveoli and airways, in addition to protein and red cells, condensates
of water can form (effusion). To this condition can contribute the tachypnea,
caused by the struggle for oxygen. Such individuals, in our understanding, are
just those whose BHC is very high due to the fact that there are a lot of
chromosomal Q-HRs in their genome that determine the density of the CC
(Ibraimov, 2003, 2017a, Ibraimov et al., 2014).
Of course, we are aware that on the basis of
only one observation one cannot make such an unambiguous and promising
conclusion. As an excuse, we can only note that: a) in itself, HAPE is not a
frequent phenomenon in high mountain medicine; b) for almost 40 years of our
Center, we have not been able to examine an individual whose HAPE diagnosis was
diagnosed by highly qualified specialists; c) no one in the world has studied
the karyotype of individuals who have endured HAPE to the subject of
chromosomal Q-HRs polymorphism. However, it would be interesting if anyone
looked at the karyotype of individuals who had endured HAPE and calculated the
number of chromosomal Q-HRs under a fluorescent microscope.
A question may arise: is there any evidence
that chromosomal Q-HRs are related to human pathology. Our experience shows
that chromosomal Q-HRs have to do with at least some purely human forms of
pathology, like atherosclerosis, obesity, drug addiction and alcoholism
(Ibraimov, 2016b, c, 2017a,b). Moreover, there is reason to believe that only a
man and two higher primates (chimpanzees and gorilla) suffer from common cold
because of the presence of chromosomal Q-HRs in their genome in addition to
C-HRs (Ibraimov, 2016a). The fact is that Q-heterochromatin is present in the
genome only in man, the chimpanzee and gorilla (see above).
Finally, there is one more important
circumstance, to date, no satisfactory animal model of HAPE has been developed.
This may indicate that, perhaps, HAPE is another form of purely human
pathology. The reason for this can be a high variability in the number of
chromosomal Q-HRs in the genome of human populations, the consequence of which
is the existence of individuals with different levels of BHC with all the
ensuing consequences.
So, how do we explain why not all people ill
with HAPE? The following assumption seems highly probable to us. Among the
animals studied, only three species of higher primates have both types of
constitutive heterochromatin – C and Q-HRs. Therefore, they must have the
highest level of BHC. However, unlike chimpanzees and gorillas, the genome of
human populations is characterized by a wide quantitative variability of
chromosomal Q-HRs. Therefore, it is possible that under all other conditions
being equal, HAPE most often develops in individuals with a large amount of
chromosomal Q-HRs in the genome.
ACKNOWLEDGMENTS
I apologize to those authors whose work is
not cited or only cited through reviews. The reason for this is only the space
limitations.
1. Al-Nassar, К.Е., Palmer, С.G., Connealy, P.М. & Рао-Lo Yu. 1981. The genetic structure
of the Kuwaiti population. II. The distribution of Q-band chromosomal
heteromorphisms. Нum Genet, 57, 423-427.
2. Arrighi, F.Е., & Hsu, Т.С. 1971. Localization
of heterochromatin in human chromosomes. Cytogenetics, 10, 81-86.
3. Buckton, К. Е., et al. 1976. С- and
Q-band polymorphisms in the chromosomes of three human populations. Аnn Нum Genet, 40, 90-112.
4. Caspersson, Т., Zech, L., & Johansson С. 1970. Differential
binding of alkilating fluorochromes in human chromosomes. Ехр Cell Res, 60,
315-319.
5. Décsey, K., Bellovits, O., & Bujdoso, G.M. 2006. Human chromosomal polymorphism in Hungarian sample. Int J Hum
Genet, 6(3), 177-183.
6. Erdtmann, В. 1982. Aspects
of evaluation, significance, and evolution of human С-band heteromorphism. Нum Genet, 61, 281-294.
7. Geraedts, J.P.М., & Pearson P.L. 1974. Fluorescent chromosome polymorphism: frequencies and segregation in а Dutch population. Clin Genet,
6, 247-257.
8. Hackett P.H., Rennie D., Levine H.D. 1976. The incidence, importance, and prophlaxis of
acute mountain sickness. Lancet 2: 1149-1155.
9. Hackett P.H. 1980. Acute mountain sickness – the clinical approach. Adv Cardiol 27:
6-10.
10. Hall W.H., Barila T.G., Metzer E.C., Gupta K.K.
1965. A clinical study of acute mountain
sickness. Arch Environ Health 10: 747-753.
11. Hamilton A.J., Cymmerman A, Black P.M. 1986. High altitude cerebral edema.
Neurosurgery 19: 841-849.
12. Hochstrasser J., Nazer A., Oelz C. 1986. Altitude edema in a Swiss Alps: observation
on the incidence and clinical course in 50 patients. Schweiz Med Wochenschr
116: 866-873.
13. Houston C.S. 1976. High altitude illness: disease with protean manifestations. JAMA
236: 2193-2195.
14. Hultgren H., Marticorena E. 1978. High altitude pulmonary edema: epidemiologic
observations in Peru. Chest 74: 372-376.
15. Hultgren H., Honigman B., Theis K., Nicholas D.
1996. High altitude pulmonary edema in a
ski resort. West J Med 163(3): 222-227.
16. Hultgren H.N. 1996. High-altitude pulmonary edema: current concepts. Ann. Rev. Med., 47:
267-284.
17. Hungerford, D. A. (1965). Leucocytes cultured from small inocula of whole blood and preparation
of metaphase chromosomes by treatment with hypotonic KCl. Stain Technol.,
40, 333-338.
18. Ibraimov, A. I. (1983). Chromosome preparations of human whole lymphocytes – an improved
technique. Clin. Genet., 24, 240-242.
http://dx.doi.org/10.1111/j.1399-0004.1983.tb00077.x
19. Ibraimov А.I., Mirrakhimov М.М., Nazarenko S.А., Axenrod Е.I. and Akbanova G.А. 1982. Нuman chromosomal polymorphism. I. Chromosomal Q-polymorphism in Mongoloid
populations of Central Asia. Hum.
Genet., 60: 1-7.
20. Ibraimov А. I. and Mirrakhimov М. М. 1982a. Human chromosomal
polymorphism. III. Chromosomal Q-polymorphism in Mongoloids of Northern Asia.
Hum. Genet., 62: 252-257.
21. Ibraimov А. I. and Mirrakhimov М. М. 1982b. Human chromosomal polymorphism. IV. Q-polymorphism in Russians living
in Kirghizia. Hum. Genet., 62:
258-260.
22. Ibraimov А. I. and Mirrakhimov М. М. 1982c. Human chromosomal
polymorphism. V. Chromosomal Q-polymorphism in African populations. Hum.
Genet., 62: 261-265.
23. Ibraimov А. I. and Mirrakhimov М. М. 1985. Q-band polymorphism in the autosomes and the Y chromosome
in human populations. In: “Progress and Topics in Cytogenetics. The Y
chromosome. Part А. Basic
characteristics of Y chromosome”. А. А. Sandberg (Ed). Alan R. Liss, Inc., New York. USA, pp. 213-287.
24. Ibraimov А. I., Mirrakhimov М. М., Axenrod Е. I. and Kurmanova G.U. 1986. Human chromosomal polymorphism. IX. Further
data on the possible selective value of chromosomal Q-heterochromatin material.
Hum. Genet., 73: 151-156.
25. Ibraimov А. I., Kurmanova G. U., Ginsburg Е. К., Aksenovich T. I. and Axenrod Е. I. 1990. Chromosomal
Q-heterochromatin regions in native highlanders of Pamir and Tien-Shan and in
newcomers. Cytobios, 63: 71-82.
26. Ibraimov А. I., Axenrod Е. 1., Kurmanova G. U. and Turapov О.А. 1991. Chromosomal
Q-heterochromatin regions in the indigenous population of the Northern part of
West Siberia and in new migrants. Cytobios,
67: 95-100.
27. Ibraimov A.I. 2003. Condensed chromatin and cell thermoregulation. Complexus, 1:
164-170. doi:10.1159/000081065
28. Ibraimov A.I., Akanov A.A., Meymanaliev T.S.,
Karakushukova A.S., Kudrina N.O., Sharipov K.O., Smailova R.D. 2013. Chromosomal Q-heterochromatin polymorphisms in
3 ethnic groups (Kazakhs, Russians and Uygurs) of Kazakhstan. Int.
J.Genet., 5(1), 121-124.
29. Ibraimov A.I., Akanov A.A., Meimanaliev T.S., Sharipov K.O., Smailova
R.D., Dosymbekova R. 2014. Human
Chromosomal Q-heterochromatin Polymorphism and Its Relation to Body Heat
Conductivity. Int. J. Genet., 6(1), 142-148.
30. Ibraimov A.I. 2015. Heterochromatin: The visible with many invisible effects. Global
Journal of Medical Research (C), Volume 15, Issue 3, Version 1.0, pp. 7-32
31. Ibraimov A.I. 2016a. Why only people and apes are ill with common cold? The possible role of
chromosomal Q-heterochromatin. J. Mol. Biol. Res., Vol. 6, No. 1, pp.
11-19. doi:10.5539/jmbr.v6n1p11
32. Ibraimov A.I. 2016b. Chromosomal Q-Heterochromatin Polymorphism in Patients with Alimentary
Obesity. Biol. Med. (Aligarh), 8: 275. doi:10.4172/0974-8369.1000275
33. Ibraimov A.I. 2016c. Chromosomal Q-heterochromatin Regions in Alcoholics and Drug Addicts.
Biol. Med. (Aligarh), 8:346. doi:10.4172/0974-8369.1000346
34. Ibraimov A.I. 2017a. Cell Thermoregulation: Problems, Advances and Perspectives. J. Mol.
Biol. Res., 7(1): 58-79. doi:10.5539/jmbr.v7n1p58
35. Ibraimov A.I. 2017b.
Chromosomal Q-Heterochromatin and
Atherosclerosis. J.Mol. Biol.Res.,
Vol. 7, No. 1; 2017. doi:10.5539/jmbr.v7n1p143
36. Kalz, L., et al., 2005. Polymorphism
of Q-band heterochromatin; qualitative and quantitative analyses of features in
3 ethnic groups (Europeans, Indians, and Turks). Int J Hum Genet, 5(2),
153-163.
37. Lobenhoffer H, Zink R, Brendel W. 1982. High altitude pulmonary edema: analysis of
166 cases. In: High Altitude
Physiology and Medicine, ed. W Brendel, R Kink. New York: Springer Verlag.
38. Lubs, H.А., et al., 1977. Racial
differences in the frequency оf Q- and С-chromosomal heteromorphism.
Nature, 268, 631-632.
39. McKenzie, W. Н,. & Lubs, Н. А. (1975). Human Q and С chromosoma1 variations: distribution and incidence. Cytogenet Cell Genet, 14, 97-115.
40. Paris Conference, 1971, and Supplement 1975. Standartization
in human cytogenetics. Birth
Defects: Original Article Series, XI,
1-84. The National Foundation, New York.
41. Pearson, P. L. 1973. The uniqueness of the human
karyotype. In: Chromosome
identification techniques and application in biology and medicine. Caspersson Т. and Zech L. (eds). New York, London. Academic Press, p. 145.
42. Pearson, P.L. 1977. Pattern of bands, polymorphism and evolution of primates. In:
Molecular structure of human chromosomes. Yunis J.J. (Ed). Acad. Press. p. 267.
43. Prokofyeva-Belgovskaya, A.A. 1986. Heterochromatic Regions of Chromosomes (in Russian). Moscow, Nauka.
44. Singh I, Khanna PK, Srivastava MC, Lal M, Roy SB,
Subramanyam CSV. 1969. Acute mountain
sickness. New Engl J Med 280: 175-184.
45. Schoene RP. 1985. Pulmonary edema at high altitude: review, pathophysiology, and update.
Clin Chest Med 6: 491-507.
46. Sophocles A. 1986. High altitude pulmonary edema in Vail, Colorado. West J Med 144:
569-573.
47. Stanyon, R., et al., (1988). Population cytogenetics of Albanians in the province of Cosenza
(Italy): frequency of Q and С band variants. Int J
Anthropol, 3(1), 14-29.
48. Yamada, К., & Hasegawa, Т. (1978). Types and frequencies of Q-variant
chromosomes in а Japanese population. Нum Genet, 44, 89-98.
QUICK LINKS
- SUBMIT MANUSCRIPT
- RECOMMEND THE JOURNAL
-
SUBSCRIBE FOR ALERTS
RELATED JOURNALS
- International Journal of Clinical Case Studies and Reports (ISSN:2641-5771)
- International Journal of Anaesthesia and Research (ISSN:2641-399X)
- Journal of Cell Signaling & Damage-Associated Molecular Patterns
- Journal of Forensic Research and Criminal Investigation (ISSN: 2640-0846)
- Ophthalmology Clinics and Research (ISSN:2638-115X)
- International Journal of AIDS (ISSN: 2644-3023)
- Oncology Clinics and Research (ISSN: 2643-055X)