Genetic Analysis of Mingrelians Reveals Long-Term Continuity of Populations in Western Georgia (Caucasus).

To elucidate the population history of the Caucasus, we conducted a survey of genetic diversity in Samegrelo (Mingrelia), western Georgia. We collected DNA samples and genealogical information from 485 individuals residing in 30 different locations, the vast majority of whom being Mingrelian speaking. From these DNA samples, we generated mitochondrial DNA (mtDNA) control region sequences for all 485 participants (female and male), Y-short tandem repeat haplotypes for the 372 male participants, and analyzed all samples at nearly 590,000 autosomal single nucleotide polymorphisms (SNPs) plus around 33,000 on the sex chromosomes, with 27,000 SNP removed for missingness, using the GenoChip 2.0+ microarray. The resulting data were compared with those from populations from Anatolia, the Caucasus, the Near East, and Europe. Overall, Mingrelians exhibited considerable mtDNA haplogroup diversity, having high frequencies of common West Eurasian haplogroups (H, HV, I, J, K, N1, R1, R2, T, U, and W. X2) and low frequencies of East Eurasian haplogroups (A, C, D, F, and G). From a Y-chromosome standpoint, Mingrelians possessed a variety of haplogroups, including E1b1b, G2a, I2, J1, J2, L, Q, R1a, and R1b. Analysis of autosomal SNP data further revealed that Mingrelians are genetically homogeneous and cluster with other modern-day South Caucasus populations. When compared with ancient DNA samples from Bronze Age archaeological contexts in the broader region, these data indicate that the Mingrelian gene pool began taking its current form at least by this period, probably in conjunction with the formation of a distinct linguistic community.

Efficacy of Kan Jang® in Patients with Mild COVID-19: A Randomized, Quadruple-Blind, Placebo-Controlled Trial.

Background and aim. This study aimed to assess the efficacy of the treatment of Kan Jang®, a fixed combination of Andrographis paniculata (Burm. F.) Wall. ex. Nees and Eleutherococcus senticosus (Rupr. & Maxim.) Maxim extracts in patients with mild symptoms of COVID-19. Methods. One hundred and forty patients received six capsules of Kan Jang® (n = 68, daily dose of andrographolides-90 mg) or placebo (n = 72) and supportive treatment (paracetamol) for 14 consecutive days in a randomized, quadruple-blinded, placebo-controlled, two-parallel-group design. The efficacy outcomes were the rate of cases turning to severe, the detection rate of coronavirus SARS-CoV-2 over the time of treatment, the duration, and the severity of symptoms (sore throat, runny nose, cough, headache, fatigue, loss of smell, taste, pain in muscles) in the acute phase of the disease. Other efficacy measures included improving cognitive and physical performance, quality of life, and the levels of inflammatory blood markers-interleukin 6 (IL-6), C-reactive protein, and D-dimer. Results. Kan Jang® significantly (p < 0.05) reduced the rate of cases turning to severe (5.36%) compared to the placebo (17.86%) and decreased the detection rate of SARS-CoV-2 virus over the time of the treatment. The statistical difference in the rates of patients with clinical deterioration in the Kan Jang treatment and placebo control groups was significant (p = 0.0176) both in the 112 patients in the included-per-protocol (IPP) analysis and in the 140 patients in the intended-to-treat (ITT) analysis (p = 0.0236); the absolute risk reduction in cases thanks to the Kan Jang treatment was 12.5%, and the number we needed to treat with Kan Jang was 8. The patient's recovery time (number of sick days at the home/clinic) was shorter in the Kan Jang group compared with the placebo group. The rate of attenuation of inflammatory symptoms in the Kan Jang® group was significantly higher, decreasing the severity of cough, sore throat/pain, runny nose, and muscle soreness compared with the placebo group. Kan Jang® significantly decreased the Wisconsin Upper Respiratory Symptoms scores compared to the placebo in the sample size of 140 patients. However, the relief of fatigue and headache and the decrease in IL-6 in the blood were observed only in a subset of 86 patients infected during the second three waves of the pandemic. Kan Jang® significantly increased physical activity and workout; however, it did not affect cognitive functions (attention and memory), quality of life score, inflammatory marker D-dimer, and C-reactive protein compared with the placebo group. Conclusions. Overall, the results of this study suggest that Kan Jang® is effective in treating mild and moderate COVID-19 irrespective of the SARS-CoV-2 variant of infection.

Spatial and temporal heterogeneity in human mobility patterns in Holocene Southwest Asia and the East Mediterranean.

We present a spatiotemporal picture of human genetic diversity in Anatolia, Iran, Levant, South Caucasus, and the Aegean, a broad region that experienced the earliest Neolithic transition and the emergence of complex hierarchical societies. Combining 35 new ancient shotgun genomes with 382 ancient and 23 present-day published genomes, we found that genetic diversity within each region steadily increased through the Holocene. We further observed that the inferred sources of gene flow shifted in time. In the first half of the Holocene, Southwest Asian and the East Mediterranean populations homogenized among themselves. Starting with the Bronze Age, however, regional populations diverged from each other, most likely driven by gene flow from external sources, which we term "the expanding mobility model." Interestingly, this increase in inter-regional divergence can be captured by outgroup-f3-based genetic distances, but not by the commonly used FST statistic, due to the sensitivity of FST, but not outgroup-f3, to within-population diversity. Finally, we report a temporal trend of increasing male bias in admixture events through the Holocene.

Efficacy of Kan Jang® in Patients with Mild COVID-19: Interim Analysis of a Randomized, Quadruple-Blind, Placebo-Controlled Trial.

Kan Jang®, the fixed combination of Andrographis paniculata (Burm. F.) Wall. ex. Nees and Eleutherococcus senticosus (Rupr. & Maxim.) Maxim extracts, is a herbal medicinal product for relieving symptoms of upper respiratory tract infections. This study aimed to assess the efficacy of Kan Jang®/Nergecov® on duration and the relief of inflammatory symptoms in adults with mild COVID-19. 86 patients with laboratory-confirmed COVID-19 and mild symptoms for one to three days received supportive treatment (paracetamol) and six Kan Jang® (daily dose of andrographolides-90 mg) or placebo capsules a day for 14 consecutive days in this randomized, quadruple-blinded, placebo-controlled, two-parallel-group study. The primary efficacy outcomes were the decrease in the acute-phase duration and the severity of symptoms score (sore throat, runny nose, cough, headache, fatigue, loss of smell, taste, pain in muscles), an increase in cognitive functions, physical performance, quality of life, and decrease in IL-6, c-reactive protein, and D-dimer in blood. Kan Jang®/Nergecov® was effective in reducing the risk of progression to severe COVID-19, decreasing the disease progression rate by almost 2.5-fold compared to placebo. Absolute risk reduction by Kan Jang treatment is 14%, the relative risk reduction is 243.9%, and the number Needed to Treat is 7.14. Kan Jang®/Nergecov® reduces the duration of disease, virus clearance, and days of hospitalization and accelerates recovery of patients, relief of sore throat, muscle pain, runny nose, and normalization of body temperature. Kan Jang®/Nergecov® significantly relieves the severity of inflammatory symptoms such as sore throat, runny nose, and muscle pain, decreases pro-inflammatory cytokine IL-6 level in the blood, and increases patients' physical performance (workout) compared to placebo. In this study, for the first time we demonstrate that Kan Jang®/Nergecov® is effective in treating mild COVID-19.

Efficacy of Adaptogens in Patients with Long COVID-19: A Randomized, Quadruple-Blind, Placebo-Controlled Trial.

Currently, no effective treatment of comorbid complications or COVID-19 long-haulers during convalescence is known. This randomized, quadruple-blind, placebo-controlled trial aimed to assess the efficacy of adaptogens on the recovery of patients with Long COVID symptoms. One hundred patients with confirmed positive SARS-CoV-2 test, discharged from COVID Hotel isolation, Intensive Care Unit (ICU), or Online Clinics, and who experienced at least three of nine Long COVID symptoms (fatigue, headache, respiratory insufficiency, cognitive performance, mood disorders, loss of smell, taste, and hair, sweatiness, cough, pain in joints, muscles, and chest) in the 30 days before randomization were included in the study of the efficacy of Chisan®/ADAPT-232 (a fixed combination of adaptogens Rhodiola, Eleutherococcus, and Schisandra) supplementation for two weeks. Chisan® decreased the duration of fatigue and pain for one and two days, respectively, in 50% of patients. The number of patients with lack of fatigue and pain symptoms was significantly less in the Chisan® treatment group than in the placebo group on Days 9 (39% vs. 57%, pain relief, p = 0.0019) and 11 (28% vs. 43%, relief of fatigue, * p = 0.0157). Significant relief of severity of all Long COVID symptoms over the time of treatment and the follow-up period was observed in both groups of patients, notably decreasing the level of anxiety and depression from mild and moderate to normal, as well as increasing cognitive performance in patients in the d2 test for attention and increasing their physical activity and workout (daily walk time). However, the significant difference between placebo and Chisan® treatment was observed only with a workout (daily walk time) and relieving respiratory insufficiency (cough). A clinical assessment of blood markers of the inflammatory response (C-reactive protein) and blood coagulation (D-dimer) did not reveal any significant difference over time between treatment groups except significantly lower IL-6 in the Chisan® treatment group. Furthermore, a significant difference between the placebo and Chisan® treatment was observed for creatinine: Chisan® significantly decreased blood creatinine compared to the placebo, suggesting prevention of renal failure progression in Long COVID. In this study, we, for the first time, demonstrate that adaptogens can increase physical performance in Long COVID and reduce the duration of fatigue and chronic pain. It also suggests that Chisan®/ADAPT-232 might be useful for preventing the progression of renal failure associated with increasing creatinine.

Actaea racemosa L. Is More Effective in Combination with Rhodiola rosea L. for Relief of Menopausal Symptoms: A Randomized, Double-Blind, Placebo-Controlled Study.

Background: The aim of this study was to assess the efficacy and safety of a new herbal preparation (Menopause Relief EP®), the hybrid combination of Actaea racemosa L. (black cohosh, BC) and Rhodiola rosea L. (RR) root extracts, compared with the most effective dose of BC extract in women with menopausal complaints. Methods: A total of 220 women were randomly assigned to receive two capsules either BC (6.5 mg), BC500 (500 mg), Menopause Relief EP® (206,5), or placebo once per day for 12 weeks. The efficacy endpoints were relief of menopausal symptoms, measured using the Kupperman Menopausal Index (KMI), Menopause Relief Score (MRS), and menopause Utian Quality of Life (UQOL) index. Results: The menopause symptom relief effects of RR-BC were significantly superior in all tests to the effects of BC and placebo after their repeated administration for 6 and 12 weeks. There was no statistically significant difference between the effects of BC and BC500 over time. RR-BC significantly improved the QOL index in patients, compared to BC, BC500, and placebo, mainly due to the beneficial effects on the emotional and health domains. Conclusions: BC is more effective in combination with RR in relief of menopausal symptoms, particularly psychological symptoms.

Genetic diversity in Svaneti and its implications for the human settlement of the Highland Caucasus.

OBJECTIVES: In this study, we characterized genetic diversity in the Svans from northwestern Georgia to better understand the phylogeography of their genetic lineages, determine whether genetic diversity in the highland South Caucasus has been shaped by language or geography, and assess whether Svan genetic diversity was structured by regional residence patterns. MATERIALS AND METHODS: We analyzed mtDNA and Y-chromosome variation in 184 individuals from 13 village districts and townlets located throughout the region. For all individuals, we analyzed mtDNA diversity through control region sequencing, and, for males, we analyzed Y-chromosome diversity through SNP and STR genotyping. The resulting data were compared with those for populations from the Caucasus and Middle East. RESULTS: We observed significant mtDNA heterogeneity in Svans, with haplogroups U1-U7, H, K, and W6 being common there. By contrast, ∼78% of Svan males belonged to haplogroup G2a, with the remainder falling into four other haplogroups (J2a1, I2, N, and R1a). While showing a distinct genetic profile, Svans also clustered with Caucasus populations speaking languages from different families, suggesting a deep common ancestry for all of them. The mtDNA data were not structured by geography or linguistic affiliation, whereas the NRY data were influenced only by geography. DISCUSSION: These patterns of genetic variation confirm a complex set of geographic sources and settlement phases for the Caucasus highlands. Such patterns may also reflect social and cultural practices in the region. The high frequency and antiquity of Y-chromosome haplogroup G2a in this region further points to its emergence there.

Colchis - Iberian Medicine or Cura Mediana

This paper reviews the ancient traditions about Colchis. It considers the legends of the Argonauts and the Golden Fleece, of Medea and the plant lore which is well established in Georgia. Many remedies and poisons are native to the area. Hippocrates is said to have visited Colchis to study local healing traditions, describing the country, with its rich flora and fauna as well as its diseases. Thus, Medea can be considered a pioneer of cosmetics, haematology, surgery and toxicology leading the way for the development of modern medicine.