ЛІКУВАННЯ ПРЕЕКЛАМПСІЇ ТА ГЕСТАЦІЙНОЇ ГІПЕРТЕНЗІЇ У ВАГІТНИХ ЗГІДНО ЄВРОПЕЙСЬКИХ РЕКОМЕНДАЦІЙ З АРТЕРІАЛЬНОЇ ГІПЕРТЕНЗІЇ (2007 Р.)

В статті проведений аналіз клінічних досліджень застосування антагоніста кальцію-нормодипіну у лікуванні прееклампсії та артеріальної гіпертензії. Доведено позитивний вплив на перебіг вагітності та стан новонароджених. Прееклампсія - це клінічний прояв неспроможності адаптаційних механізмів материнського організму адекватно забезпечити потреби плода, що розвивається. Частота дистресу плода та затримки внутрішньоутробного його розвитку у вагітнихз артеріальною гіпертензією (АГ) в 2,5 раза вища, ніжу жінокз нормальним артеріальним тиском (АТ), а ризик перинатальної втрати плода збільшується пропорційно рівню АТ [2, 4, 10]. Медикаментозна терапія прееклампсії та АГ у вагітних спрямована на покращання прогнозу для матері та новонародженого і повинна враховувати інтереси обох пацієнтів [1,2,3, 5, 7, 8, 9]

Рибоводно-технологічне обґрунтування рециркуляційної аквасистеми для африканського кларієвого сома Clarias gariepinus (Burchell, 1822)

The advantages of Clarias gariepinus over other valuable species of fish raised in closed water supply systems are rapid growth, the ability to obtain marketable products in 6 months, unpretentiousness to the conditions of detention, valuable taste: clary catfish meat contains polyunsaturated fatty acids ( omega-3) and meets the requirements of a balanced healthy diet. The study was conducted on one of the farms for growing clary catfish, which is part of the Union of Aqua Farmers of Ukraine LLC “Aquapromgroup” in the Odesa region. To optimize the work of the farm for growing commercial Claria catfish in ultrasound, the use of polycyclic (8-cyclic) method instead of 2-cyclic, which currently operates, will allow more efficient use of production capacity, technological equipment and sell 127,784 tons of fish, which is 2.4 times more. To implement the technology it is necessary to grow the following number of fish: at the 1st stage – 24000 specimens, at the 2nd stage – 20400 specimens, at the 3rd stage – 17748 specimens, at the 4th stage – 15973 of each of 8 cycles. During the year the farm sells 127.784 copies. clary catfish with an average weight of 1 kg. Farm costs for compound feed: for feed for fry (“Biomar”) – 234432 UAH, for feed for other age groups of clary catfish – 2879860 UAH. The total cost of feed – 3114292 UAH. If all the requirements of the 8-cycle technological process of growing catfish in closed water supply installations (total volume of pools – 131 m3) the cost of 1 kg of fish will be 39 hryvnias, the farm will receive 3960300 hryvnias of gross profit from sales of marketable products, the profitability of production will be 79.5 %. Therefore, during the performance of this work, we proved the advantage of using the polycyclic method of growing clary catfish in closed water supply installations.Перевагою Clarias gariepinus щодо інших цінних видів риб, яких вирощують в установках замкнутого водопостачання, є насамперед: швидкий темп росту, можливість отримати товарну продукцію за 6 місяців, невибагливість до умов утримання, цінні смакові якості: м’ясо кларієвого сома містить поліненасичені жирні кислоти (омега-3) і відповідає вимогам збалансованої здорової їжі. Дослідження проводилось на одній з ферм з вирощування кларієвого сома, яка входить до спілки аквафермерів України ООО “Аквапромгруп”, що в Одеській області. Для оптимізації роботи господарства з вирощування товарного кларієвого сома в УЗВ застосування поліциклічного (8-циклічного) методу замість 2-циклічного, який діє на теперішній час, дозволить раціональніше використовувати виробничі потужності, технологічне обладнання та реалізувати 127,784 тонни риби, що у 2,4 раза більше. Для реалізації технології необхідно вирощувати таку кількість риби: на 1 етапі – 24000 екз., на 2 етапі – 20400 екз., на 3 етапі – 17748 екз., на 4 етапі – 15973 кожного з 8 циклів. За рік господарство реалізує 127784 екз. кларієвого сома середньою масою 1 кг. Витрати господарства на комбікорма: на корм для мальків (“Біомар”) – 234432 грн, на корм для інших вікових груп кларієвого сома – 2879860 грн. Загальні витрати на корм – 3114292 грн. За дотримання всіх вимог 8-циклічного технологічного процесу вирощування кларієвого сома в установках замкнутого водопостачання (загальний об’єм басейнів – 131 м3) собівартість 1 кг риби становитиме 39 гривень, господарство отримає 3960300 грн валового прибутку від реалізації товарної продукції, рентабельність виробництва становитиме 79,5 %. Отже, під час виконання даної роботи нами було доведено перевагу використання поліциклічного методу вирощуванні кларієвого сома в установках замкнутого водопостачання

Suppressor Analysis Reveals a Role for SecY in the SecA2-Dependent Protein Export Pathway of Mycobacteria

All bacteria use the conserved Sec pathway to transport proteins across the cytoplasmic membrane, with the SecA ATPase playing a central role in the process. Mycobacteria are part of a small group of bacteria that have two SecA proteins: the canonical SecA (SecA1) and a second, specialized SecA (SecA2). The SecA2-dependent pathway exports a small subset of proteins and is required for Mycobacterium tuberculosis virulence. The mechanism by which SecA2 drives export of proteins across the cytoplasmic membrane remains poorly understood. Here we performed suppressor analysis on a dominant negative secA2 mutant (secA2 K129R) of the model mycobacterium Mycobacterium smegmatis to better understand the pathway used by SecA2 to export proteins. Two extragenic suppressor mutations were identified as mapping to the promoter region of secY, which encodes the central component of the canonical Sec export channel. These suppressor mutations increased secY expression, and this effect was sufficient to alleviate the secA2 K129R phenotype. We also discovered that the level of SecY protein was greatly diminished in the secA2 K129R mutant, but at least partially restored in the suppressors. Furthermore, the level of SecY in a suppressor strongly correlated with the degree of suppression. Our findings reveal a detrimental effect of SecA2 K129R on SecY, arguing for an integrated system in which SecA2 works with SecY and the canonical Sec translocase to export proteins

Time-trend and variations in the proportion of second-eye cataract surgery

<p>Abstract</p> <p>Background</p> <p>Despite recommendations for greater use of second-eye cataract surgery and the bilateral progression of the disease, there is a substantial proportion of unmet need for this treatment. Few studies have explored the factors associated with second-eye cataract surgery utilisation. The objective of our study was to estimate the proportion of second-eye cataract surgery, evaluate its time-trend, and explore differences in utilisation by patients' gender, age, and region of residence.</p> <p>Methods</p> <p>All senile cataract surgeries performed between 1999 and 2002 in the public health system of Catalonia (Spain) were obtained from the Minimum Data Set. The proportion of second-eye surgery from November 2000 to December 2002 was calculated. The time-trend of this proportion was characterised through linear regression models with the logarithmic transformation of time.</p> <p>Results</p> <p>The proportion of second-eye surgery was 30.0% and showed an increasing trend from 24.8% (95% Confidence Interval [CI] 21.6; 26.1) in November 2000 to 31.8% (95% CI 31.4; 33.6) in December 2002. This proportion was 1.9% (95% CI 0.9; 2.9) higher in women (p < 0.001) and held constant across time. Male patients aged less than 60 had the lowest proportion (22.6%; 95% CI 22.4; 22.9) and females between 70 and 79 had the highest proportion (27.4%; 95% CI 26.9; 27.9). The time-trend for the proportion of second-eye surgery in those aged over 80 years was greater than for younger ages, showing an increase of 9% at the end of the period for both males and females. Variations between regions decreased over time because regions with the lowest initial proportions of second-eye surgery (approximately 17%) showed a greater increase over the study period.</p> <p>Conclusion</p> <p>We predict greater utilization of second-eye surgery in patients aged 70 to 79 years and in women. A greater increase in the utilisation rates of second-eye surgery is expected in the regions with lower proportions and in older patients. The observed trend suggests that there will be a substantial proportion of unmet need for bilateral surgery.</p

Geographical variations in the benefit of applying a prioritization system for cataract surgery in different regions of Spain

<p>Abstract</p> <p>Background</p> <p>In Spain, there are substantial variations in the utilization of health resources among regions. Because the need for surgery differs in patients with appropriate surgical indication, introducing a prioritization system might be beneficial. Our objective was to assess geographical variations in the impact of applying a prioritization system in patients on the waiting list for cataract surgery in different regions of Spain by using a discrete-event simulation model.</p> <p>Methods</p> <p>A discrete-event simulation model to evaluate demand and waiting time for cataract surgery was constructed. The model was reproduced and validated in five regions of Spain and was fed administrative data (population census, surgery rates, waiting list information) and data from research studies (incidence of cataract). The benefit of introducing a prioritization system was contrasted with the usual first-in, first-out (FIFO) discipline. The prioritization system included clinical, functional and social criteria. Priority scores ranged between 0 and 100, with greater values indicating higher priority. The measure of results was the waiting time weighted by the priority score of each patient who had passed through the waiting list. Benefit was calculated as the difference in time weighted by priority score between operating according to waiting time or to priority.</p> <p>Results</p> <p>The mean waiting time for patients undergoing surgery according to the FIFO discipline varied from 1.97 months (95% CI 1.85; 2.09) in the Basque Country to 10.02 months (95% CI 9.91; 10.12) in the Canary Islands. When the prioritization system was applied, the mean waiting time was reduced to a minimum of 0.73 months weighted by priority score (95% CI 0.68; 0.78) in the Basque Country and a maximum of 5.63 months (95% CI 5.57; 5.69) in the Canary Islands. The waiting time weighted by priority score saved by the prioritization system varied from 1.12 months (95% CI 1.07; 1.16) in Andalusia to 2.73 months (95% CI 2.67; 2.80) in Aragon.</p> <p>Conclusion</p> <p>The prioritization system reduced the impact of the variations found among the regions studied, thus improving equity. Prioritization allocates the available resources within each region more efficiently and reduces the waiting time of patients with greater need. Prioritization was more beneficial than allocating surgery by waiting time alone.</p

МОЛЕКУЛЯРНОЕ МАРКИРОВАНИЕ ОБРАЗЦОВ ГОРОХА ОВОЩНОГО

The paper presents the results of research on the presence in genomes of pea hybrid materials of the DNA regions complementary to the primers that are associated with the biochemical characteristics and resistance to powdery mildew.В работе представлены результаты исследований гибридного материала гороха овощного на наличие в их геномах участков ДНК, комплементарных ряду праймеров, связанных с биохимическими характеристиками и устойчивостью к настоящей муч нистой росе

Dynamic Evolution of Pathogenicity Revealed by Sequencing and Comparative Genomics of 19 Pseudomonas syringae Isolates

Closely related pathogens may differ dramatically in host range, but the molecular, genetic, and evolutionary basis for these differences remains unclear. In many Gram- negative bacteria, including the phytopathogen Pseudomonas syringae, type III effectors (TTEs) are essential for pathogenicity, instrumental in structuring host range, and exhibit wide diversity between strains. To capture the dynamic nature of virulence gene repertoires across P. syringae, we screened 11 diverse strains for novel TTE families and coupled this nearly saturating screen with the sequencing and assembly of 14 phylogenetically diverse isolates from a broad collection of diseased host plants. TTE repertoires vary dramatically in size and content across all P. syringae clades; surprisingly few TTEs are conserved and present in all strains. Those that are likely provide basal requirements for pathogenicity. We demonstrate that functional divergence within one conserved locus, hopM1, leads to dramatic differences in pathogenicity, and we demonstrate that phylogenetics-informed mutagenesis can be used to identify functionally critical residues of TTEs. The dynamism of the TTE repertoire is mirrored by diversity in pathways affecting the synthesis of secreted phytotoxins, highlighting the likely role of both types of virulence factors in determination of host range. We used these 14 draft genome sequences, plus five additional genome sequences previously reported, to identify the core genome for P. syringae and we compared this core to that of two closely related non-pathogenic pseudomonad species. These data revealed the recent acquisition of a 1 Mb megaplasmid by a sub-clade of cucumber pathogens. This megaplasmid encodes a type IV secretion system and a diverse set of unknown proteins, which dramatically increases both the genomic content of these strains and the pan-genome of the species

Eribulin-trastuzumab combination in HER2-positive metastatic breast cancer: updated results from a Russian observational study

Introduction. The standard of 1st line treatment of HER2+ metastatic breast cancer (mBC) is double blockade with trastuzumab and pertuzumab + taxane, 2nd line – Trastuzumab-emtazine. There are no standards for further treatment, as well as the optimal drug sequence. Expansion of the arsenal of therapeutic possibilities and the use of new combinations will certainly improve the results of treatment of this category of patients and increase their life expectancy.Aim. We sought to describe treatment patterns of  eribulin  and clinical outcomes of  metastatic HER2-positive breast cancer treated with eribulin  plus trastuzumab combination in  academic institutions and community oncology practices across the Russian Federation.Materials and methods. Patients treated with eribulin anytime between Jan, 2014 and Sep, 2019 with a diagnosis of MBC were identified by 23 providers from Russia. Providers retrospectively reviewed the health records and abstracted selected data points into an electronic case report form for each eligible patient.Results. 100 HER2-positive pts received eribulin in combination with trastuzumab. Median age was 55 (31–80) yrs and ECOG status 0–3. 67% pts had visceral metastases. Eribulin was administered as 1st and 2nd line to 23 (23%) pts, 3rd line to 31 (31%) pts, 4th line and later to 46 (46%). Median number of cycles was 5 (2–27). ORR was 12%, SD – 72%, SD &gt; 6 months – 23%, PD – 16%. Clinical efficacy rate achieved in 35%. Median PFS was 5.07 months (95% CI 4.021–6.119). According to the ER-status the response to eribulin and trastuzumab was different. ORR was 18.8%, SD 72.9% in pts with ER-positive MBC (n = 48) and 5.8% and 71.2% respectively in ER-negative MBC (n = 52). Median PFS was 6.97 months (95% CI 3.924–10.016) in pts with ER-positive MBC and 4.67 months (95% CI 3.841–5.499) in ER-negative MBC (р = 0.3). The combination was well tolerated: dose reductions were required in 12% pts, withdrawal due to toxicity in 4% pts. The most common type of toxicity was hematological with neutropenia Gr III-IV in 14 (14%) pts. Peripheral neuropathy Gr III was observed in 5 (5%) pts. No cardiotoxicity was detected.Conclusions. This is the real-life data of clinical outcomes for patients receiving eribulin plus trastuzumab for HER2-positive MBC throughout the Russian Federation. Our experience with eribulin plus trastuzumab demonstrates that this combination may be a potential effective treatment option for HER-2 positive MBC patients

СОБСТВЕННЫЙ ОПЫТ ПРИМЕНЕНИЯ ЭРИБУЛИНА В УСЛОВИЯХ РЕАЛЬНОЙ КЛИНИЧЕСКОЙ ПРАКТИКИ Г. МОСКВЫ И МОСКОВСКОЙ ОБЛАСТИ

Introduction. Eribulin, an non-taxane microtubule inhibitor, has been registered in Russia for patients with locally advanced or metastatic breast cancer (mBC) who received at least one chemotherapy regimen for a advanced disease, previous therapy should include anthracyclines and taxanes in adjuvant or metastatic setting, except the patients who could not be prescribed these drugs. We present our experience with eribulin in real clinical practice in Moscow and the Moscow Region.Patients and methods. We conducted a retrospective analysis of the experience with the use of eribulin in Moscow and the Moscow Region in 202 patients with mBC from January 2016 to February 2017 to assess the effectiveness and safety of the drug. All patients received previous therapy with anthracyclines and taxanes for locally advanced and / or metastatic cancer. The average age of patients at the time of inclusion in the analysis was 5 years (28–81). The status of the general condition on the ECOG 0-1 scale was registered in 81.3 % (100 / 123) of patients, the status of ECOG 2-3 in 18.7 % (23 / 123) of patients. The median of the number of courses of chemotherapy with eribulin is 4 (2–17). Patients received eribulin in 1-7 chemotherapy lines for metastatic disease. The average number of affected organs is 2 (1–5).Results. Complete response (CR) was in 3 (2 %) patients. Partial response (PR) was in 24 (15.7 %) patients, stabilization of the disease – in 89 (58. 2 %). Progression of the disease was recorded in 37 (24.1 %) patients. The median of progression-free survival (PFS) on the therapy was 4.64 (95 % CI 2.97-6.87) months. Stabilization of the disease for more than 6 months was registered in 28 (18.3 %) patients. The most significant toxicity was neutropenia and polyneuropathy (21 patients (10.4 %) and 7 patients (3.5 %), respectively).Dose reduction due to neutropenia was required by 26 patients (12.9 %). The objective response rate (ORR) depended on the chemotherapy line: in 1-3 lines the efficacy of the treatment was higher: the ORR was 21.6 %, compared to the 4th and subsequent lines – 12.3 %, respectively. With HER2-positive mBC, eribulin showed clinically significant results in combination with trastuzumab.Conclusions. Our analysis confirms that eribulin has a predictable and manageable safety profile, is an effective drug for the treatment of patients with different subtypes of mBC in a real clinical setting.Введение. Эрибулин – ингибитор динамики микротрубочек нетаксанового ряда, зарегистрирован в России для пациентов с местнораспространенным или метастатическим раком молочной железы (мРМЖ), получившим ранее не менее одного режима химиотерапии по поводу распространенного заболевания; предшествующая терапия должна включать антрациклины и таксаны в адъювантном режиме или в условиях метастатической формы заболевания, за исключением тех пациентов, которым не могли назначаться данные препараты. В настоящей работе представлен собственный опыт применения эрибулина в условиях реальной клинической практики г. Москвы и Московской области.Пациенты и методы. Проведен ретроспективный анализ опыта применения эрибулина в г. Москве и Московской области у 202 пациентов с мРМЖ с января 2016 по февраль 2017 г. для оценки эффективности и безопасности препарата. Все больные получили предшествующую терапию с использованием антрациклинов и таксанов по поводу местнораспространенного и / или метастатического рака. Средний возраст пациентов на момент включения в анализ составил 58 лет (28–81). Статус общего состояния по шкале ECOG 0–1 зарегистрирован у 81,3 % (100 / 123) больных, статус ЕCOG 2–3 – у 18,7 % (23 / 123) пациентов. Медиана числа проведенных курсов химиотерапии эрибулином – 4 (2–17). Пациенты получали эрибулин в 1–7 линиях химиотерапии по поводу метастатической формы заболевания. Среднее количество пораженных органов – 2 (1–5).Результаты. Полные регрессии (ПР) отмечены у 3 (2 %) больных, частичная регрессия (ЧР) – у 24 (15,7 %) пациентов, стабилизация заболевания – у 89 (58,2 %). Прогрессирование болезни зафиксировано у 37 (24,1 %) пациентов. Медиана выживаемости без прогрессирования (ВБП) на терапии эрибулином мРМЖ составила 4,64 мес. (95 % ДИ 2,97–6,87). Стабилизация заболевания более 6 мес. зарегистрирована у 28 (18,3 %) больных. Наиболее значимой токсичностью стали нейтропения и полинейропатия (21 (10,4 %) и 7 (3,5 %) пациентов соответственно). Редукция дозы эрибулина в связи с развитием нейтропении потребовалась 26 (12,9 %) больным.Частота объективного ответа (ЧОО) при терапии эрибулином зависела от линии химиотерапии: в 1–3 линиях эффективность лечения была выше – ЧОО составила 21,6 % по сравнению с 4-й и последующими линиями с ЧОО в 12,3 %. При HER2-положительном мРМЖ эрибулин продемонстрировал значительно лучшие результаты по ВБП в комбинации с трастузумабом по сравнению с монотерапией (медиана 4,64 мес. (95 % ДИ 2,94–6,6) и 2,58 мес. (95 % ДИ 2,15–3,6) соответственно).Выводы. Проведенный анализ подтверждает, что эрибулин, обладая предсказуемым и управляемым профилем безопасности, является эффективным препаратом для терапии пациентов с различными подтипами мРМЖ в условиях реальной клинической практики