Buy coke Vahdat
Buy coke VahdatBuy coke Vahdat
__________________________
📍 Verified store!
📍 Guarantees! Quality! Reviews!
__________________________
▼▼ ▼▼ ▼▼ ▼▼ ▼▼ ▼▼ ▼▼
▲▲ ▲▲ ▲▲ ▲▲ ▲▲ ▲▲ ▲▲
Buy coke Vahdat
These datasets underpin the analysis presented in the agency's work. Most data may be viewed interactively on screen and downloaded in Excel format. All countries. Topics A-Z. The content in this section is aimed at anyone involved in planning, implementing or making decisions about health and social responses. Best practice. We have developed a systemic approach that brings together the human networks, processes and scientific tools necessary for collecting, analysing and reporting on the many aspects of the European drugs phenomenon. Explore our wide range of publications, videos and infographics on the drugs problem and how Europe is responding to it. All publications. More events. More news. We are your source of drug-related expertise in Europe. We prepare and share independent, scientifically validated knowledge, alerts and recommendations. About the EUDA. The content of this summary does not necessarily reflect the official opinions of the European Union, nor the official opinion of the Republic of Tajikistan, and should be seen as the product of CADAP 5. Updated: August Studies on the prevalence of drug use among the population of Tajikistan were not carried out in In total, 5 respondents were interviewed, of which 2 The study found that the female respondents had a slightly higher awareness of the existence of drugs than the males. Some Among all respondents, Some 1. The survey results showed that However, When asked about drug use, 0. The consumption of inhalants was the most prevalent. According to the responses, 1. The use of marijuana or hashish was second most popular, with 0. The first experience with drugs most often took place at the age of 16 and usually the drug was marijuana, amphetamines, or tranquillisers. In a series of educational, sports and cultural events aimed at promoting a healthy lifestyle were organised. Participants were given information about the problems of drug use in modern society and its consequences. Health bulletins were issued and health information prepared in both the Tajik and Russian languages. Articles were published in newspapers and magazines and awareness-raising programmes were broadcast on three TV channels Channel One, Safina, and Jahonnamo and on the Republican radio. Anti-drug events are also organised annually to coincide with the International Day against Drug Abuse and Illicit Trafficking 26 June. Studies to estimate the population of opiate users, including injecting drug users IDUs , were not carried out in Drug treatment is carried out in the Republic of Tajikistan in specialised drug treatment facilities. The State guarantees anonymous drug treatment. In a total of 1 people received inpatient treatment in substance abuse treatment centres. Of these, The number of drug addicts who received hospital treatment in increased by The main strategic focus of this programme included:. As of 31 December , the country had 3 officially registered HIV cases cumulative number , of which The HIV prevalence rate was HIV cases have been registered in 66 of the 68 districts of the country. The average estimated number of HIV-positive people in the country ranges between 6 —10 Moreover, in recent years, the number of newly reported HIV cases among females has increased almost 2. Thus, in the proportion of women among registered new cases was 8. In , of the total number of registered HIV cases, In the country registered new cases of HIV infection, of which Among the newly registered HIV cases, people The number of reported cases of hepatitis C virus HCV in was According to the Centre for Health Statistics of the Ministry of Health of Tajikistan, in there were cases of syphilis infection among the general population, of which were male and were female. The official data from Tajikistan provide very limited information on the number of deaths related to drug use. Drug treatment is carried out in the Republic of Tajikistan at specialised drug treatment facilities. Services provided by specialised drug treatment agencies in the country include inpatient and outpatient care, anti-relapse therapy, rehabilitation programmes, work with drug addicts and efforts to prevent substance abuse. Treatment of drug dependence in the Republic of Tajikistan is conducted mainly at public drug treatment facilities, including:. The availability of substance abuse treatment beds in the Republic of Tajikistan is 4 per inhabitants. Harm reduction programmes are implemented to minimise the consequences of drug use. Geographically, the HR programme covers almost the whole of the country. In the Government of the Republic of Tajikistan reviewed and supported the letter of the Ministry of Health of the Republic of Tajikistan asking it to consider a pilot implementation of a programme of OST. Up to patients have received OST at this centre. This is the first gender-sensitive project in the Republic of Tajikistan. The centre provided low-threshold services laundry, showers, communication, leisure, food, sanitary napkins and legal advice and referral to doctors. In this centre, 62 were re-adaptation clients, 40 of whom abstained during the reported period, and two patients were referred for further rehabilitation to the Tangai Republican Rehabilitation Centre. These clients received low-threshold services and advice at the drop-in centre. Five hundred motivational packages were given to the most active clients. Harm reduction programmes were first introduced in the Republic of Tajikistan in in Dushanbe, Khujand and Khorog, mainly in the form of needle exchange programmes NEPs and via the distribution of information materials. In Kulyab a hour drop-in centre for drug users was opened by the non-government organisation NGO Anis. The NGO Volunteer, which implemented a programme in the Gorno-Badakhshan Autonomous Oblast GBAO , provided services 9 times during the reporting period, including services related to: social support 1 ; prevention 2 ; healthcare 2 ; information and counselling 1 ; psychological care and support ; legal services ; and social services The Social Bureau covered 1 clients people injecting drugs, 9 sex workers, 24 people living with HIV, 89 people with tuberculosis, 52 ex-prisoners with HBV and 15 with HCV, 1 minor at risk, and vulnerable women. As part of this programme, one mobile trust point and four NSPs were established, located on the premises of the National Tuberculosis Hospital in urban health centres Nos 2, 12 and During the reporting period, RAN served 1 clients. A total of syringes were exchanged and 23 condoms were distributed. In a total of 4 The steady increase in seizures of cannabis, primarily hashish, continued in , with the result that cannabis comprised This significant change in the type of drug seized was a result of an increase in the areas sown with cannabis in Afghanistan in recent years. The impurities in the samples of heroin that were seized were found to be from the manufacturing process — 6-monoacetylmorphine and acetylcodeine — and cutting agents of extrinsic origin — caffeine, acetaminophen paracetamol and dextromethorphan. No extrinsic substances were found in the narcotic opium seized in Starch-containing substances were found in just a few samples. The physical appearance of the cannabis resin that was seized was either in the form of a rod or of material compressed into rectangular tiles. The dimensions of tiles varied within the following ranges: width 14—16 cm, length 21—23 cm, thickness 2—3 cm. Drug prices in Tajikistan increase in proportion to the distance from the state border. The legislation of the Republic of Tajikistan in the field of drug control is based on the rules and recommendations of the United Nations Drug Treaties and Conventions , , , of which Tajikistan became a signatory in and The main purpose of Law No. Law No. The main objectives of the law are the protection of the rights and legitimate interests of people suffering from substance abuse and addiction, establishing bases and procedures for the provision of substance abuse treatment, and the protection and security of professionals providing drug treatment services. Article 6 of the Constitution guarantees the following types of drug treatment and social protection:. The main objective of this law is the realisation of the national policy and international agreements of Tajikistan in the sphere of licit trafficking of narcotic substances, psychotropic substances and precursors, countermeasures of their illicit trafficking, prevention of drugs and toxicomania and rendering of narcological assistance to people suffering from drug addiction and toxicomania. The main task of the law is to protect the rights and legal interests of people suffering from narcological diseases, establish grounds and a procedure for rendering narcological assistance and to protect the rights of medical and other workers rendering narcological assistance. According to Article 6 of the Law, the Government guarantees the following kinds of narcological assistance and social protection:. Chapter 22 of the Criminal Code of the Republic of Tajikistan effective from 1 September stipulates responsibility for the following violations of the law related to drug issues:. The National Strategy of the Republic of Tajikistan in the field of the control of narcotic drugs is aimed at preventing the use of the territory of the state by transnational organised drug traffickers to smuggle narcotics, international commitments and the establishment of strict control over the licit movement of narcotic drugs, ensuring the effective fight against drug trafficking, guaranteeing the medical care of patients with drug addiction and increasing international cooperation in this area. One of the measures taken by the Government of the Republic of Tajikistan in the field of drug control is the coordination of bodies at all levels of society in order to synchronise the activities of law enforcement agencies in the fight against drug trafficking, as well as the relevant ministries and agencies in the control of drug trafficking, psychotropic substances and precursors, and drug prevention. The main body that coordinates ministries, departments and organisations in the prevention of drug abuse, regardless of their form of ownership, is the Coordinating Council on the prevention of drug abuse, approved by Decree No. According to the decree, regional, city, and district councils for the coordination of drug prevention activities were established under republican subordination in the Gorno-Badakhshan Autonomous Oblast, Sughd and Khatlon regions, the city of Dushanbe, and other cities and districts. The Coordinating Council is recognised as the supervisory body of the interaction of ministries, departments and state bodies in the conduct of activities aimed at the prevention of the non-medical use of narcotic drugs and psychotropic and other drugs. Homepage Quick links Quick links. GO Results hosted on duckduckgo. Main navigation Data Open related submenu Data. Latest data Prevalence of drug use Drug-induced deaths Infectious diseases Problem drug use Treatment demand Seizures of drugs Price, purity and potency. Drug use and prison Drug law offences Health and social responses Drug checking Hospital emergencies data Syringe residues data Wastewater analysis Data catalogue. Selected topics Alternatives to coercive sanctions Cannabis Cannabis policy Cocaine Darknet markets Drug checking Drug consumption facilities Drug markets Drug-related deaths Drug-related infectious diseases. Recently published Findings from a scoping literature…. Penalties at a glance. Frequently asked questions FAQ : drug…. FAQ: therapeutic use of psychedelic…. Viral hepatitis elimination barometer…. EU Drug Market: New psychoactive…. EU Drug Market: Drivers and facilitators. Statistical Bulletin home. Quick links Search news Subscribe newsletter for recent news Subscribe to news releases. Breadcrumb Home Publications Tajikistan country overview Tajikistan country overview Contents Drug use among the general population and young people Prevention Problem drug use Treatment demand Drug-related infectious diseases Drug-related deaths Treatment responses Harm reduction responses Drug markets and drug-law offences National drug laws National drug strategy Coordination mechanism in the field of drugs References. Agency on Statistics under the President of the Republic of Tajikistan.
His blood cultures initially grew Peptostreptococcus spp and he was started on penicillin and gentamicin. Repeat blood cultures, drawn 48 h later, became.
Buy coke Vahdat
Official websites use. Share sensitive information only on official, secure websites. Correspondence: dott. OFCs orofacial clefts are among the most frequent congenital defects, but their etiology has yet to be clarified. OFCs affect different structures and functions with social, psychological and economic implications in children and their families. Studies focusing on the risk factors of NSOFCs were selected, leading to 62 case-control and randomized clinical trials. Risk factors were categorized into non-modifiable and modifiable. The first group includes genetic polymorphisms, gender of the newborn, ethnicity, and familiarity. Within the second group, risk factors that can only be modified before conception consanguinity, parental age at conception, socio-economical and educational level, area of residency and climate , and risk factors modifiable before and after conception weight, nutritional state, acute and chronic diseases, psychophysical stress, licit and illicit drugs, alcohol, smoke, pollutants and contaminants have been distinguished. This study provides a wide overview of the risk factors of NSOFCs, focusing on modifiable ones, to suggest new perspectives in education, prevention, medical interventions and clinical research. Keywords: alcohol, cleft lip and palate, contaminants, drugs, orofacial clefts, pregnancy, prevention, pollutants, risk factors, smoke. Babies with OFCs manifest problems with phonation, feeding, hearing, and aesthetic and psychological discomfort. They require short- and long-term multidisciplinary health care \[ 2 \]. In addition, these infants show higher mortality in the first years of life and up to 55 years of age and an increased risk of cancer \[ 3 \]. Embryologically, the face is derived from five processes, namely the frontonasal and the two maxillary and mandibular processes \[ 4 \]. The frontal process originates from the medial and lateral nasal processes bordering the bilateral nasal pits \[ 5 \]. Between weeks 4 and 12 of intrauterine life, the development of the lip and palate occurs by migration into the first pharyngeal arch of cells derived from the neural crest. Following complex processes of cell differentiation, by fusion of the nasal placodes with the maxillary process, the upper lip and primary palate are formed. Subsequent elongation and thickening of the palatine processes result in their fusion and differentiation into bone and muscle tissue, creating the hard palate and soft palate \[ 6 \]. Failure of fusion of maxillary and middle nasal processes results in a cleft lip CL. Failure of fusion of the palatine processes results in the cleft palate CP \[ 5 , 6 \]. In addition, there is the subclass cheilognathoschisis CL and alveolus \[ 6 , 7 \]. The initial of the letter of the anatomical part involved is written uppercase or lowercase depending on whether the cleft is complete or partial. According to the aetiology, OFCs are classified into syndromic and non-syndromic. Syndromic OFCs more than originate from genetic, chromosomal, and teratogenic abnormalities and are associated with the presence or absence of other congenital and developmental and physical abnormalities. Generally, OFCs are prevalent in the male sex. CL is present in In general, CP results in the most frequent CL is more frequent on the left and in males, in Scientific researchers have confirmed that different DNA methylation in embryonic development causes the occurrence of OFCs \[ 16 \]. The analysis of blood samples from non-syndromic children with CL, CLP and CP revealed genomic sequences previously linked to OFCs and new sequences, with different methylation occurring in the embryonic period \[ 17 \]. These results support the hypothesis that the three subtypes may have different aetiology \[ 3 , 18 \]. Besides data confirming the role of genetics in the aetiology of OFCs, scientific studies and epidemiological data show that environmental risk factors e. Maternal complications include miscarriage, elective termination of pregnancy due to prenatal identification of CAs, hyperemesis gravidarum, and anemia due to insufficient intake of folate and vitamin B12 \[ 46 , 47 , 48 \]. Among fetal conditions, a study conducted in Brazil counts preterm birth gestational age less than 37 weeks before the stage of fetal weight gain, which is often associated with cesarean delivery \[ 49 \]. This systematic review aims to distinguish between non-modifiable and modifiable factors, focusing our attention on the latter, to take preventive, educational and therapeutic measures to reduce the occurrence of NSOFCs. The search strategy was built by using a combination of words that matched the purpose of our investigation, whose primary focus is the risk factors associated with OFCs. The articles were selected using the following inclusion criteria: 1 studies only on human subjects; 2 open access studies; 3 clinical trials, cohort studies and randomized controlled trials; and 4 English language. Two reviewers M. The selected articles were downloaded into Zotero version 6. Any discrepancies between the two authors were resolved by consulting a senior reviewer F. In the first case, the consulted databases were Pubmed 64 , Scopus , Cochrane , and Web of Science ; in the second case, the consulted database were Pubmed 9 , Scopus , Cochrane 17 , and Web of Science Hence, only studies that focus on the association between OFCs and risk factors were selected, by the analysis of the title and abstract. Studies dealing with other aspects of OFCs—for example, hereditary risk factors, associated diseases and syndromes, prenatal diagnosis, treatment and consequences—were excluded , because they were off-topic. Duplicates were removed, leading to 63 records selected, and after eligibility, 62 studies were selected for qualitative analysis Figure 2. The risk factors identified were classified into non-modifiable or modifiable. Among the latter group, we made a distinction between 1 risk factors that can be prevented through educational programs before conception, namely, consanguinity, parental age at conception, socio-economical and educational level, area of residency and climate, and 2 risk factors modifiable both before and after conception, namely weight, nutritional state, acute and chronic diseases, psychophysical stress, licit and illicit drugs, alcohol, smoke, pollutants and contaminants. This systematic review aims to extrapolate from the literature of the last 10 years the main risk factors of NSOFCs, classifying them as non-modifiable and modifiable. Therefore, they will be treated in the paragraph of folate and vitamin deficiency, as their impact on embryogenesis becomes significant when an insufficient intake of folate and vitamin B Gender can be considered both a protective and a risk factor for OFCs. In some cases, studies identified correlations of gender with a specific type of OFCs. According to Sakran et al. Ethnic differences could potentially influence the incidence of OFCs. However, estimates of these relationships vary significantly throughout the research. This could be explained by differences in the measurement and categorization of ethnic groupings and variations in the classification of oral clefts \[ 54 \]. The international literature identifies the Asian, white and indigenous races as having higher anomaly prevalence rates of OFCs. Belonging to a non-white race could be a protective factor for the occurrence of OFCs \[ 55 \]. These findings are also demonstrated by Shibukawa et al. The survey of Kapos et al. Family history is considered the most critical risk factor in the development of clefts \[ 55 \]. The analysis of Silva et al. In addition, Sakran et al. Ly at al. In the study of Noorollahian et al. The mechanism underlying this correlation is the likelihood of sharing alleles that are similar through descents \[ 55 \]. Most genetic clefts have developed when consanguinity and family history have been discovered in a family simultaneously. A case-control study by Sakran et al. Similarly, Cheshmi et al. In Iran, the prevalence of this custom is much more than the global medium due to cultural norms \[ 47 \]. Compared to Western developed nations, where this sort of marriage is not particularly frequent, the high incidence of marriage in very traditional developing countries such as Iran greatly raises the risk of OFCs. These findings agree with other reports analyzed, which support the role of genetics in the incidence of oral clefts \[ 59 , 60 \]. Silva et al. They also emphasize the need for genetic counseling for this community \[ 55 \]. According to de Carvalho et al. Conversely, for other authors, parental age was not significantly associated with OFCs \[ 46 , 56 \]. In regard to the potential protective effect of parental age, it is difficult to identify a range considered not at risk for OFCs because, in this field, the data in the literature are in contrast, especially about paternal age. If Sakran et al. The same authors identified a maternal age between 26 and 35 years as protective \[ 23 \]. In conclusion, these data reveal that protective age ranges have been identified for both parents 26—35 years and 25—29 years for mothers and fathers, respectively. According to various research, fathers with lower socioeconomic positions and education levels are more likely to generate children with oral clefts \[ 52 , 61 \]. A case-control study by Lupo et al. These results may significantly impact the prevention of health inequities \[ 62 \]. The research of Figuireido et al. Although this investigation did not find conclusive evidence linking this factor, the underlying cause may be related to prenatal care, nutrition, and other lifestyle choices \[ 52 \]. Few research studies have looked at the connection between rural maternal residency and CLP risk, even though inequalities between rural and urban areas have been observed for numerous health and birth outcomes. Generally, moms who lived in rural areas were at a greater risk of having a baby with oral clefts \[ 52 , 63 , 64 , 65 , 66 \]. Kapos et al. In agreement with the poor literature, they showed that babies born to women who reside in rural regions have a greater chance of developing NSOFCs than babies born to moms who live in urban areas \[ 54 \]. Noorollahian et al. An international study by Figuiereido et al. Teratogenic consequences of increased body core temperature have been demonstrated \[ 21 , 67 , 68 \]. Soim et al. Despite research suggesting that warm temperature leads to worse pregnancy outcomes, authors found no statistically significant increased risk of neural tube malformations across all climatic regions. Future research should improve exposure and thoroughly review the topic \[ 69 \]. Obesity is a significant public health problem in developing countries \[ 30 , 70 \]. BMI is considered normal if it is between Maternal obesity can be responsible for congenital disabilities \[ 71 \] as it can cause hyperglycemia, hyperinsulinemia, oxidative stress, systemic inflammation, and nutritional deficiencies that can compromise the development of the fetus \[ 72 , 73 \]. Kutbi et al. Although previous revisions have found a 1. Otherwise, few authors have shown a correlation between maternal underweight and OFCs \[ 77 , 78 \]. George et al. They found a strong negative influence only for CL and CP if the two factors are associated, especially in women with lower-than-normal BMI \[ 79 \]. In this study, a reduction in the odds ratio for smoking was reported with increasing BMI, possibly for the ability of adipose tissue to retain the lipophilic chemicals of smoke \[ 79 , 80 \]. However, a higher-than-normal BMI is not protective against the pathogenetic effects of smoking \[ 79 \]. The maternal nutritional state is crucial to drastically reduce the appearance of congenital abnormalities CAs in newborns. For instance, a strict maternal vegetarian diet increases 15 times the risk of OFCs in newborns when compared to omnivorous people \[ 32 \]. Low levels of vitamin B12 and folate are often detected among vegetarian women, and a diet deficient in folate and vitamin B12, especially during early pregnancy, has been linked to OFCs \[ 32 \]. One study showed a reduced amount of folate in the Indian population due to the type of vegetarian diet and mode of cooking food. Folate in vegetables is sensitive to heat, so it is destroyed during steaming \[ 81 \]. Curiously, some studies deleted the relationship between cleft and specific foods, namely liver, sprue potatoes and caffeine-containing beverages. Caffeine belongs to the methylxanthine class and elevates the homocysteine level, interfering with the metabolic pathways of B6-vitamin \[ 48 \]. Studies concerning liver consumption showed mixed results. Conversely, for others, preventing OFCs would not be sufficient \[ 81 \]. Potatoes usually are considered a reliable source of nutrients. Still, when sprouted, they can contain high levels of glycoalkaloid solanine which is considered toxic and teratogenic for the human body. Periconceptional intake of this food may increase the risks of developing OFCs and neural tube defects \[ 83 \]. A stressful event can cause an increase in cortisol in the maternal blood and therefore in the fetus. The teratogenic effect of corticosteroids CTS has long been demonstrated \[ 84 , 85 \]. The enzyme 11B-hydroxysteroid dehydrogenase type 2 11beta HSD2 responsible for regulating the passage of CTS through the placental barrier is down-regulated in case of stress \[ 41 , 42 \]. Moreover, in the early stages of pregnancy—a critical moment for the formation of the facial massif—this enzyme is less represented \[ 86 \]. The consequent increase in circulating CTS levels can also cause hyperinsulinemia and insulin resistance with negative effects on the development of the fetus \[ 42 , 87 , 88 \]. It has been shown that taking vitamin B6 supplements helps reduce the harmful effects of CTS because this vitamin acts as a tissue receptor suppressor for these hormones \[ 89 \]. Stress also increases catecholamines that reduce uterine blood flow and increase the risk of hypoxic damage to the fetus \[ 84 , 90 , 91 \]. Ingstrup et al. In , Sato et al. As a concerned maternal physical activity, its role has also been examined in the work environment. However, further studies are needed to investigate further and confirm the correlation between maternal physical activity and OFCs \[ 94 \]. Diabetes mellitus DM is a metabolic disease characterized by hyperglycemia. The regulation of blood glucose levels occurs thanks to insulin production by the pancreatic beta cells, a hormone that controls the entry and use of glucose into cells. This condition resolves on its own after delivery, but affected women have a greater risk of developing type 2 DM in subsequent years. Guariguata et al. In , Trindade-Suedam et al. This study demonstrated that hyperglycemia during pregnancy increases the risk of incidence of OFCs in newborns \[ 31 \]. Therefore, rigorous and systematic control of maternal blood glucose levels is necessary during the gestational period to prevent the risk of OFCs and other CAs \[ 31 \]. In , Figueiredo et al. A temporary poor blood supply causes it in the heart, resulting in a lack of oxygen to the cardiac tissue. This condition is usually aggravated by physical exertion and emotional stress and is alleviated by taking nitro-glycerine \[ 97 \]. Maternal angina pectoris MAP and myocardial infarction are ischemic events that rarely occur during pregnancy \[ 98 \]. The study of Czeizel et al. Otherwise, the association of MAP with cigarette smoke increases the risk of developing clefts \[ 29 , \]. A genetic correlation between the two issues has also been hypothesized since hyperhomocysteinemia is associated with both a higher risk of MAP \[ , \] and a higher incidence of OFCs \[ \], as well as genes related to stress \[ \]. However, the limitations of this study are linked to the low incidence of MAP in pregnant women and, therefore, to the small number of cases and controls \[ 29 \]. Lip and palate development occurs during the early stages of pregnancy. In a recent study, Sakran et al. Hyperthermia, often associated with viral infections, has been seen to play an important role in the onset of the cleft \[ 81 , \]. The most common conditions related to OFCs generally occur during early gestation and are the common cold, acute respiratory infections, influenza, pulpitis, cholecystitis, acute urinary tract infections, and pelvic inflammatory diseases \[ 49 \]. These data suggest the importance of vaccines for pregnant women, such as the flu vaccine \[ 81 \]. Although genetic polymorphisms are included among the non-modifiable risk factors, adequate folate and b12 supplementation in pregnancy compensate for enzyme deficiencies and the accumulation of teratogenic metabolites \[ \]. The enzyme MTHF reductase converts 5,MTHF to 5-MTHF, which is the active metabolite of folic acid and acts as a cofactor in several biochemical reactions, for example, the conversion of amino acid homocysteine to methionine, which lead to the methylation of DNA, RNA and histones proteins, one of the main mechanisms underlying gene expression regulation. Reduced levels of the active form of folic acid and accumulation of homocysteine impair cell differentiation and tissue growth during embryogenesis, leading to neural tube defects and OFCs. The common origin of these CAs is that the neural crest cells of orofacial tissues and teeth are situated in the dorsolateral regions of the neural tube. In addition, hyperhomocysteinemia is an independent risk factor for cerebrovascular disease associated with atherosclerosis, hypertension, inflammation, neurodegenerative diseases, pregnancy complications, and congenital malformation \[ \]. Even if it is clear that the supplementation with folate and cobalamin during pregnancy significantly reduce the prevalence of OFCs and neural tube defects both in mice and human \[ \], the correlation of OFCs with the most common polymorphisms of folate pathway, namely c. Jahanbin et al. Instead, Komiyama et al. Recently, Machado et al. Conversely, according to Martinelli et al. ProArg and of the single nucleotide polymorphism rs, belonging to transcobalamin 2 TCN2 and cystathionine beta-synthase CBS , respectively \[ , \]. This would agree with the theory that embryonic hypoxia, during the first three months of pregnancy, can hinder the correct formation of facial processes \[ 81 , \]. It has also been shown that the increase in inflammatory cytokines that occurs, for example, during pulpitis, can be responsible for the problem \[ 81 \]. The same authors also point out that there is a higher risk of CP in the case of maternal hyperthyroidism in the first 14 weeks of gestation \[ 81 \]. Epilepsy also exposes the fetus to a greater risk of OFCs. Still, in these cases, the potential teratogenic effect of the antiepileptic drugs that the mother takes must also be taken into considered \[ 81 , , , \]. The children of women who suffered from migraines during pregnancy proved to be more predisposed to the development of clefts. Still, in this case, the influence of drugs taken to alleviate the symptoms must be investigated \[ 81 , , , \]. According to this article \[ 81 \], even the spasmolytic and anti-pain drugs used for cholelithiasis, urolithiasis, and neuro-musculoskeletal pain syndromes can be identified as the main culprits of the problem \[ \]. Thirty-two percent of mothers used drugs during all the phases of pregnancy and, generally, several papers find a significant correlation between drugs and the occurrence of specific types of OFCs, especially during early gestation Table 2 \[ 31 , 46 , 53 , \]. The most prescribed drugs in pregnancy are vitamins, followed by antibiotics. Current evidence is quite ambiguous regarding maternal supplementation with folic acid and multivitamins for preventing OFCs. In contrast, Roosendaal et al. Specifically, the antibiotics most used are beta-lactams, followed by sulphonamides and macrolides. Antibiotics are prescribed more frequently in the second trimester, especially to women under 25 years \[ \]. Although the prescription of antibiotics in pregnancy has slightly increased in the last decade, the association between OFCs and antibiotics is still a matter of debate in the literature, also for molecules classically considered safe in pregnancy \[ \]. The exact pathogenetic mechanisms underlying the teratogenic effects of antibiotics have not yet been clarified. One of the best-known is trimethoprim inhibition of the folate methylation cycle \[ \]. According to a large cohort study, antibiotics use in early pregnancy does not represent a significant risk factor for NSOFCs, even if the risk increases for specific classes and selected periods. Controversial data concern amoxicillin, the antibiotic most used to treat respiratory and urinary infections in pregnancy and classified in the pregnancy category B drug by the USFDA U. Food and Drug Administration. CTS are widely used as anti-inflammatory and immune-modulating drugs during pregnancy and induce pulmonary maturity in the fetus. Above all, they are widely used during pregnancy in dermatological formulations for treating rashes, psoriasis, dermatitis and eczema, and in inhalation formulations to treat rhinitis \[ \]. The increase in endogenous CTS can interfere with the fusion of the palatal shelves in mice. Considering that the fetus has a lower endogenous level of CTS and that the enzyme 11beta HSD2 is less represented in the early stage of pregnancy, it can be argued that even low doses of CTS and dermatological formulations, such as betamethasone, can overcome placenta, reach fetal circulation and cause teratogenic effects during embryogenesis \[ 86 \]. As already discussed above, the level of endogenous cortisol produced in excess in case of maternal stress can also contribute to the risk of OFCs \[ 87 , \]. No association was found with topic CTS \[ \]. Regarding the timing of exposure, the most critical period of exposure to CTS is during weeks 1—4 and 5—8 after conception, followed by exposure only during 4 weeks before conception and exposure during weeks 5—8 and 9—12 after conception. Ondansetron is a 5-HT3 receptor antagonist commonly used to contrast hyperemesis pregnancy. According to the retrospective cohort study of Huybrechts et al. Specifically, the type of oral cleft found was CP. Topiramate is an anticonvulsant drug commonly used to treat epilepsy, bipolar disorder and migraine also during pregnancy. Data are referred to a period from 3 months before conception through one month after delivery \[ \]. Finally, other drugs associated with OFCs are reported in the most recent literature, namely anticonvulsants, retinoic acid, analgesics, benzodiazepines, antidepressants, stimulants, and anti-hypertensive drugs, and drugs containing iron and folate \[ 31 , 34 , 53 \]. It increases the risk of OFCs associated with other craniofacial anomalies by nearly three times \[ 31 \]. Prenatal opioid exposure and other drugs can have severe and immediate consequences for newborns. Mullen et al. Maternal exposure to numerous chemicals that are released into the air as a result of the incomplete combustion of tobacco and other organic compounds such as cooking and heating fuels have been shown to cause cracks; these substances include polycyclic aromatic hydrocarbons PAHs , carbon monoxide CO and heavy metals \[ \]. Smoking increases levels of carbon monoxide, which has a high affinity for hemoglobin, thus resulting in reduced oxygen supply to the placenta. At the same time, nicotine constricts the uterine wall causing hypoxia in embryogenetic tissues during the palate genesis. Hypoxia induces malformations in the maxillary region \[ 38 \]. Several researchers, including Shaw and Romitti —, have shown that cigarette smoke can alter the expression of the gene involved in palatogenesis, transforming growth factor alfa TFGA \[ 37 , , \]. Krapels et al. The biological mechanisms underlying cleft lip and palate are hidden in the DNA and depend on a defect in the TFGA gene, which is responsible for organizing the structure of the face and palate during embryogenetic processes; the mechanism of interaction between smoke and gene remains unknown \[ , \]. TFGA is responsible for promoting the synthesis of the extracellular matrix and the migration of mesenchymal cells and ensuring palate strength and fusion. When normal, this portion of DNA is insensitive to the negative effect of smoking, but when altered, it becomes vulnerable to smoking. If the fetus inherits the defect from both mother and father, it cannot detoxify itself and suffers the insult of cigarette smoke, which can result in malformation \[ , \]. Regarding drug type, licit drugs such as tobacco, stimulants and antidepressants have been shown to increase the risk of orofacial malformations; this correlation was not observed for illicit drugs such as cocaine and cannabis due to the small sample size or lack of control \[ 31 \]. Several authors have amply demonstrated the role of alcohol in the genesis of the palatal cleft. However, it varies with dose, frequency, and mechanisms of toxin transfer from the mother to the embryo \[ , , \]. Exaggerated alcohol consumption is associated with craniofacial malformations characterized by reduced growth of the central nervous system and neurodevelopment \[ \]. Between the fifth and tenth week of pregnancy is the period when the structures forming the palate and lip fuse. An important aspect relates to the amount of alcohol and frequency during pregnancy. One author has shown that consuming five or more glasses of alcohol in an evening can be particularly detrimental to fetal development because it exposes the fetus to a higher concentration of alcohol in the blood than someone who consumes the same amount over a more extended period. Another important aspect is genetic susceptibility, defined by maternal alcohol metabolizing genes ADH1C haplotype gene associated with reduced alcohol metabolism \[ , \]. Maternal exposure to gaseous air pollutants in the preconceptionally period and early stages of gestation revealed a positive correlation with the risk of developing NSOFCs. CP cases were related only to NO 2 exposure \[ 43 , 44 \]; no correlation was observed with O 3 ozone \[ 43 , 45 \]. The biological mechanism by which gaseous air pollutants can cause OFCs remains unclear. Water pollution also proved a significant risk factor. Figueiredo et al. Environmental contaminants include arsenic, pesticides, and heavy metals. Arsenic is widespread in the environment in organic and inorganic forms. Exposure to it can occur through occupational or dietary exposure, drinking water, or eating foods containing it, such as rice, vegetables, fruits, and shellfish. The study by Suhl et al. However, the paternal influence in these malformations is controversial. According to Ly et al. Maternal occupational exposure in the periconceptional period to organic solvents aromatic and chlorinated—which are widely found commercially in the form of degreasers, cosmetics, paints, detergents, or pesticides—has not shown a positive correlation with the occurrence of OFCs in offspring \[ , \]. The aim of this systematic review was to demonstrate that NSOFCs recognize multiple modifiable risk factors and to highlight the interactions that genetics, environment, habits of daily life, diet and pathology have on the onset of this congenital abnormality. Herein, risk factors were classified into non-modifiable or modifiable. The first group includes genetic polymorphisms, gender of the newborn, ethnicity and familiarity. Among the latter group, there are risk factors that can be prevented through educational programs and lifestyle interventions before conception aimed at planning a pregnancy safely, namely consanguinity, parental age at conception, socio-economical and educational level, area of residency, climate. Risk factors that are modifiable both before conception and during pregnancy include weight, nutritional state, psychophysical stress, acute and chronic diseases, licit and illicit drugs, alcohol, smoke, pollutants and contaminants. The gender of the newborn is more associated with specific forms of OFCs, although conclusions are contradictory. Caucasian, Asian, and indigenous ethnicities have higher rates of OFCs anomalies than non-white ethnicities. Familiarity is one of the major contributors to the occurrence of OFCs, especially if it coexists with consanguinity. Although OFC is a multifactorial disease, the genetic component has proven to be critical. This consideration stems from the high prevalence of OFCs in babies born from consanguineous relationships, which are uncommon in Western countries but common in less developed or developing countries e. More crucial is to understand the role of modifiable risk factors in reducing the incidence of OFCs in newborns. It is preferable to plan a pregnancy between 26—35 years for women and 25—29 years for men because, in these age ranges, the risk of OFCs is sensibly reduced, as well as to educate populations to avoid consanguineous marriages. Few studies have examined the relationship between the area of residency and climate and the risk of OFCs, leading to the conclusion that even if there is a weak association between heat events and OFCs, the climate has no effect on the onset of this pathology. This aspect, however, may be linked to another risk factor identified: socioeconomic status. A low level of socioeconomic development, which is common in rural areas and underdeveloped or developing countries, creates conditions that favor the onset of this pathology: consanguineous marriages, reduced access to care, insufficient intake of nutrients, abnormal BMI, unhealthy lifestyles and habits, exposure to pollution and contaminants. Acute and chronic diseases, e. Consequently, it is necessary to promote screening, vaccination, and health education plans to identify early pregnancies at risk and provide targeted medical or lifestyle interventions. Nutritional deficiencies, particularly a lack of vitamin B12 and folate, are strongly linked to changes in neural tube defects, especially in carriers of the folate pathway genetic polymorphisms—a strict vegetarian diet carries a fold increase in the risk of OFCs when compared to meat-consuming diets. Psychophysical stress is a relevant environmental factor that is typical of modern times. This condition causes hormonal and biochemical changes in the pregnant woman, which may favor the onset of fetal development changes. It is preferable to treat psychological stress with non-pharmacological interventions because antidepressants are counted among the drugs associated with the risk of OFCs. Intense physical exercise has shown a weak association with the onset of OFCs. Although the protective role of moderate physical activity has been established, more research is needed to investigate and understand the relationship between maternal physical activity, psychophysical stress, and OFCs. Drugs are widely used in pregnancy. Antibiotics, CTS, and specific drugs such as ondansetron and topiramate have received the most attention in literature, but their role is controversial. It is generally accepted that the intake of these drugs during the first trimester of pregnancy or before conception exposes the newborn to an increased risk of CAs, including OFCs. Licit or illicit use of opioids deserves special attention, because causes a threefold increase in the risk of developing OFCs and other craniofacial congenital anomalies. Furthermore, a link has been established between the onset of NSOFCs and the use and abuse during pregnancy of substances such as tobacco, antidepressants, and stimulants, whereas few studies have examined the role of illicit drugs such as cocaine and cannabis due to quantitative and ethical constraints in recruiting study samples. Several studies have examined the effects of passive and active smoking on fetal development. Even though the recognized mechanisms of action differ, all studies agree that smoking and tobacco combustion products increase the risk of OFCs in infants by about Alcohol consumption during pregnancy is strongly associated with OFCs, especially in cases of abuse or large intakes. It has been shown that consuming five or more glasses of alcohol in one evening can be harmful to fetal development. Most of the articles evaluated in the review identified smoking, alcohol, and drugs as major predisposing environmental factors for the development of NSOFCs, but many authors emphasized the limitations of studies on this interaction, which are typically due to the impossibility of quantifying exposure to these three causative factors. Finally, periconceptional and early gestational maternal exposure to gaseous air pollutants, such as CO, NO 2 , and SO 2 , showed a positive correlation with the risk of developing CP. Conversely, an association with heavy metals or inorganic solvents, was not discovered. Although multiple interactions and risk factors for the development of NSOFCs have been identified, the reviewers would like to highlight that the studies relate predominantly to mothers. The few studies that also take in consideration the paternal risk factor are referred to age, familiarity, area of residency, socioeconomic status, educational level, and environmental pollutants. Therefore, future research should focus on the paternal role, as well as on the mechanisms of action of environmental risk factors. At the same time, this review points out that most of the risk factors associated with cleft are preventable or modifiable. Educational programs, prevention campaigns, medical and lifestyle interventions are mandatory to obtain a reduction in the incidence of new cases of OFCs in the next years. Conceptualization, A. Giuseppina Malcangi , G. Grazia Marinelli , F. Grazia Marinelli and G. Giuseppina Malcangi , C. Giuseppina Malcangi , A. Giuseppina Malcangi , D. All authors have read and agreed to the published version of the manuscript. This section collects any data citations, data availability statements, or supplementary materials included in this article. As a library, NLM provides access to scientific literature. Children Basel. Find articles by Angelo Michele Inchingolo. Find articles by Maria Celeste Fatone. Find articles by Giuseppina Malcangi. Find articles by Pasquale Avantario. Find articles by Fabio Piras. Find articles by Assunta Patano. Find articles by Chiara Di Pede. Find articles by Anna Netti. Find articles by Anna Maria Ciocia. Find articles by Elisabetta De Ruvo. Find articles by Fabio Viapiano. Find articles by Giulia Palmieri. Find articles by Merigrazia Campanelli. Find articles by Antonio Mancini. Find articles by Vito Settanni. Find articles by Vincenzo Carpentiere. Find articles by Grazia Marinelli. Find articles by Giulia Latini. Find articles by Biagio Rapone. Find articles by Gianluca Martino Tartaglia. Find articles by Ioana Roxana Bordea. Find articles by Antonio Scarano. Find articles by Felice Lorusso. Find articles by Daniela Di Venere. Find articles by Francesco Inchingolo. Find articles by Alessio Danilo Inchingolo. Find articles by Gianna Dipalma. Maria Grazia Cagetti : Academic Editor. Open in a new tab. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. Retinoic acid. Not reported.
Buy coke Vahdat
Note by Turkey. The information in this document with reference to “Cyprus” relates to the southern part of the Island. There is no single.
Buy coke Vahdat
Buy coke Vahdat
Her left ventricular systolic function normalized during that hospitalization. In , the patient was readmitted to the hospital with chest discomfort and ST-.
Buy coke Vahdat
Buy coke Vahdat
Buy coke Vahdat
Buy coke Vahdat