[The social, demographic and professional characteristics of general practitioners and district therapists of state and private sectors of health care].

The article presents comparative analysis of demographic, social and professional characteristics of general practitioners and district therapists in state and private medical organizations. Sociological, statistical and analytical research methods were applied. The study was carried out on the basis of polyclinics of both Moscow Health Department and Moscow private health care sector. The sampling consisted of 399 questionnaires subjected to statistical processing. It is established that in state and private medical organizations, in this group of physicians prevail women 36-55 years old, born in the Russian Federation, in Moscow, married, having children and assessing one's income level as average. Most of them received their higher education in Moscow, graduated residency in therapy and have no medical category or academic degree. The professional experience consists 10 years or more. All physicians in state polyclinics hold more than one position and in private polyclinics 8.6% of physicians are underemployment. In the state sector, paternalistic model of communication with patient is preferable, in the private sector - a collegiate one. In the state sector, the collegiate management style of CEO is convenient and in the private sector - collegiate or dynamic one. In both sectors, adhocratic organizational culture is comfortable. Against the background of readiness to proceed working in current conditions, work in another sector is not excluded. The material factor is considered as main driver of professional motivation. The social, demographic and professional characteristics of general practitioners and district physicians in both sectors of health care in the main are similar, but have their own characteristics.

Characterization and development of transcriptome-derived novel EST-SSR markers to assess genetic diversity in Chaetomium globosum.

Chaetomium globosum Kunze, an internationally recognized biocontrol fungus. It mycoparasitizes various plant pathogens and produce antifungal metabolites to suppress the growth of pathogenic fungi. Lack of detailed genome level diversity studies has delimited the development and utilization of potential C. globosum strains. The present study was taken to reveal the distribution, identification, and characterization of expressed sequence tag-simple sequence repeats (EST-SSRs) in C. globosum. RNA-Seq experiment was performed for C. globosum potential isolate Cg2 (AY429049) using Illumina HiSeq 2500. Reference-guided de novo assembly yielded 45,582 transcripts containing 27,957 unigenes. We generated a new set of 8485 EST-SSR markers distributed in 5908 unigene sequences with one SSR locus distribution density per 6.1 kb. Six distinct classes of SSR repeat motifs were identified. The most abundant were mononucleotide repeats (51.67%), followed by tri-nucleotides (36.61%). Out of 5034 EST-SSR primers, 50 primer pairs were selected and validated for the polymorphic study of 15 C. globosum isolates. Twenty-two SSR markers showed average genetic polymorphism among C. globosum isolates. The number of alleles (Na) per marker ranges from 2 to 4, with a total of 74 alleles detected for 22 markers with a mean polymorphism information content (PIC) value of 0.4. UPGMA hierarchical clustering analysis generated three main clusters of C. globosum isolates and exhibited a lower similarity index range from 0.59 to 0.85. Thus, the newly developed EST-SSR markers could replace traditional methods for determining diversity. The study will also enhance the genomic research in C. globosum to explore its biocontrol potential against phytopathogens. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03794-7.

Glucometrics in the first week of critical illness and its association with mortality / Glucometría en la primera semana de enfermedad crítica y su asociación con la mortalidad

Objective Evaluation of glucometrics in the first week of ICU stay and its association with outcomes. Design Prospective observational study. Setting Mixed ICU of teaching hospital. Patients Adults initiated on insulin infusion for 2 consecutive blood glucose (BG) readings ≥180mg/dL. Main variables of interest Glucometrics calculated from the BG of first week of admission: hyperglycemia (BG>180mg/dL) and hypoglycemia (BG<70mg/dL) episodes; median, standard deviation (SD) and coefficient of variation (CV) of BG, glycemic lability index (GLI), time in target BG range (TIR). Factors influencing glucometrics and the association of glucometrics to patient outcomes analyzed. Results A total of 5762 BG measurements in 100 patients of median age 55 years included. Glucometrics: hyperglycemia: 2253 (39%), hypoglycemia: 28 (0.48%), median BG: 169mg/dL (162–178.75), SD 31mg/dL (26–38.75), CV 18.6% (17.1–22.5), GLI: 718.5 [(mg/dL)2/h]/week (540.5–1131.5) and TIR 57% (50–67). Diabetes and higher APACHE II score were associated with higher SD and CV, and lower TIR. On multivariate regression, diabetes (p=0.009) and APACHE II score (p=0.016) were independently associated with higher SD. Higher SD and CV were associated with less vasopressor-free days; lower TIR with more blood-stream infections (BSI). Patients with higher SD, CV and GLI had a higher 28-day mortality. On multivariate analysis, GLI alone was associated with a higher mortality (OR 2.99, p=0.04). Conclusions Glycemic lability in the first week in ICU patients receiving insulin infusion is associated with higher mortality. Lower TIR is associated with more blood stream infections (AU)

Objetivo Evaluación de la glucometría en la primera semana de estancia en la UCI y su asociación con los resultados. Diseño Estudio observacional prospectivo. Ámbito UCI mixta de hospital docente. Pacientes Adultos que iniciaron una infusión de insulina para dos lecturas consecutivas de glucosa en sangre (GS) ≥180mg/dl. Principales variables de interés Glucometría calculada a partir de la GS de la primera semana de ingreso: episodios de hiperglucemia (GS >180mg/dl) e hipoglucemia (GS <70mg/dl); mediana, desviación estándar (DE) y coeficiente de variación (CV) de GS, índice de labilidad glucémica (ILG), tiempo en el rango objetivo de GS (TIR). Resultados Se incluyeron un total de 5.762 GS en 100 pacientes con una mediana de edad de 55años. Glucometría: hiperglucemia: 2.253 (39%), hipoglucemia: 28 (0,48%), mediana GS: 169mg/dl, DE 31mg/dl, CV 18,6%, ILG: 718,5 [(mg/dl)2/h]/semana, TIR 57%. La diabetes y una puntuación APACHEII más alta se asociaron con una DE y un CV más altos y una TIR más baja. En la regresión multivariada, la diabetes (p=0,009) y la puntuación APACHEII (p=0,016) se asociaron de forma independiente con una DE más alta. La DE y el CV más altos se asociaron con menos días sin vasopresores; menor TIR, con más infecciones del torrente sanguíneo (ITS). En el análisis multivariado, el ILG solo se asoció con una mayor mortalidad (OR: 2,99, p=0,04). Conclusiones La labilidad glucémica en la primera semana en pacientes de UCI que reciben infusión de insulina se asocia con mayor mortalidad. Una TIR más baja se asocia con más ITS (AU)

Glucometrics in the first week of critical illness and its association with mortality.

OBJECTIVE: Evaluation of glucometrics in the first week of ICU stay and its association with outcomes. DESIGN: Prospective observational study. SETTING: Mixed ICU of teaching hospital. PATIENTS: Adults initiated on insulin infusion for 2 consecutive blood glucose (BG) readings ≥180mg/dL. MAIN VARIABLES OF INTEREST: Glucometrics calculated from the BG of first week of admission: hyperglycemia (BG>180mg/dL) and hypoglycemia (BG<70mg/dL) episodes; median, standard deviation (SD) and coefficient of variation (CV) of BG, glycemic lability index (GLI), time in target BG range (TIR). Factors influencing glucometrics and the association of glucometrics to patient outcomes analyzed. RESULTS: A total of 5762 BG measurements in 100 patients of median age 55 years included. Glucometrics: hyperglycemia: 2253 (39%), hypoglycemia: 28 (0.48%), median BG: 169mg/dL (162-178.75), SD 31mg/dL (26-38.75), CV 18.6% (17.1-22.5), GLI: 718.5 [(mg/dL)2/h]/week (540.5-1131.5) and TIR 57% (50-67). Diabetes and higher APACHE II score were associated with higher SD and CV, and lower TIR. On multivariate regression, diabetes (p=0.009) and APACHE II score (p=0.016) were independently associated with higher SD. Higher SD and CV were associated with less vasopressor-free days; lower TIR with more blood-stream infections (BSI). Patients with higher SD, CV and GLI had a higher 28-day mortality. On multivariate analysis, GLI alone was associated with a higher mortality (OR 2.99, p=0.04). CONCLUSIONS: Glycemic lability in the first week in ICU patients receiving insulin infusion is associated with higher mortality. Lower TIR is associated with more blood stream infections.

A prospective international observational prevalence study on prone positioning of ARDS patients: the APRONET (ARDS Prone Position Network) study.

INTRODUCTION: While prone positioning (PP) has been shown to improve patient survival in moderate to severe acute respiratory distress syndrome (ARDS) patients, the rate of application of PP in clinical practice still appears low. AIM: This study aimed to determine the prevalence of use of PP in ARDS patients (primary endpoint), the physiological effects of PP, and the reasons for not using it (secondary endpoints). METHODS: The APRONET study was a prospective international 1-day prevalence study performed four times in April, July, and October 2016 and January 2017. On each study day, investigators in each ICU had to screen every patient. For patients with ARDS, use of PP, gas exchange, ventilator settings and plateau pressure (Pplat) were recorded before and at the end of the PP session. Complications of PP and reasons for not using PP were also documented. Values are presented as median (1st-3rd quartiles). RESULTS: Over the study period, 6723 patients were screened in 141 ICUs from 20 countries (77% of the ICUs were European), of whom 735 had ARDS and were analyzed. Overall 101 ARDS patients had at least one session of PP (13.7%), with no differences among the 4 study days. The rate of PP use was 5.9% (11/187), 10.3% (41/399) and 32.9% (49/149) in mild, moderate and severe ARDS, respectively (P = 0.0001). The duration of the first PP session was 18 (16-23) hours. Measured with the patient in the supine position before and at the end of the first PP session, PaO2/FIO2 increased from 101 (76-136) to 171 (118-220) mmHg (P = 0.0001) driving pressure decreased from 14 [11-17] to 13 [10-16] cmH2O (P = 0.001), and Pplat decreased from 26 [23-29] to 25 [23-28] cmH2O (P = 0.04). The most prevalent reason for not using PP (64.3%) was that hypoxemia was not considered sufficiently severe. Complications were reported in 12 patients (11.9%) in whom PP was used (pressure sores in five, hypoxemia in two, endotracheal tube-related in two ocular in two, and a transient increase in intracranial pressure in one). CONCLUSIONS: In conclusion, this prospective international prevalence study found that PP was used in 32.9% of patients with severe ARDS, and was associated with low complication rates, significant increase in oxygenation and a significant decrease in driving pressure.

Incidence, risk factors and associated mortality of central line-associated bloodstream infections at an intensive care unit in northern India.

OBJECTIVE: To evaluate the incidence, risk factors and associated mortality of central line-associated bloodstream infection (CLABSI) in an adult intensive care unit (ICU) in India. DESIGN: This prospective observational study was conducted over a period of 16 months at a tertiary care referral medical center. SETTING: We conducted this study over a period of 16 months at a tertiary care referral medical center. PARTICIPANTS: All patients with a central venous catheter (CVC) for >48 h admitted to the ICU were enrolled. INTERVENTION AND MAIN OUTCOME MEASURES: Patient characteristics included were underlying disease, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation (APACHE II) scores and outcome. Statistical analysis of risk factors for their association with mortality was also done. RESULTS: There were 3235 inpatient-days and 2698 catheter-days. About 46 cases of CLABSI were diagnosed during the study period. The overall rate of CLABSI was 17.04 per 1000 catheter-days and 14.21 per 1000 inpatient-days. The median duration of hospitalization was 23.5 days while the median number of days that a CVC was in place was 17.5. The median APACHE II and SOFA scores were 17 and 10, respectively. Klebsiella pneumoniae was the most common organism (n = 22/55, 40%). Immunosuppressed state and duration of central line more than 10 days were significant factors for developing CLABSI. SOFA and APACHE II scores showed a tendency towards significance for mortality. CONCLUSIONS: Our results underscore the need for strict institutional infection control measures. Regular training module for doctors and nurses for catheter insertion and maintenance with a checklist on nurses' chart for site inspection and alerts in all shifts are some measures planned at our center.

Design, Development and Optimization of S (-) Atenolol Floating Sustained Release Matrix Tablets Using Surface Response Methodology.

The objective of this present investigation was to develop and formulate floating sustained release matrix tablets of s (-) atenolol, by using different polymer combinations and filler, to optimize by using surface response methodology for different drug release variables and to evaluate the drug release pattern of the optimized product. Floating sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: Hydroxypropyl methylcellulose, sodium bicarbonate as a gas generating agent, polyvinyl pyrrolidone as a binder and lactose monohydrate as filler. The 3(2) full factorial design was employed to investigate the effect of formulation variables on different properties of tablets applicable to floating lag time, buoyancy time, % drug release in 1 and 6 h (D1 h,D6 h) and time required to 90% drug release (t90%). Significance of result was analyzed using analysis of non variance and P < 0.05 was considered statistically significant. S (-) atenolol floating sustained release matrix tablets followed the Higuchi drug release kinetics that indicates the release of drug follows anomalous (non-Fickian) diffusion mechanism. The developed floating sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet.

High anion gap refractory metabolic acidosis as a critical presentation of endosulfan poisoning.

Organochloride insecticides are chlorinated cyclic hydrocarbons. One of such insecticides is endosulfan (6,7,8,9,10-10 hexachloro 1,5,5a,6,9,9a-hexahydro-6-methano-2,4,3-hexadithioxanthiep in 3-oxide) and it has been widely used in agriculture since 1960. The uncontrolled use of these compounds in developing countries has resulted in the deaths of animals and humans. Characteristic clinical signs following acute exposure are indicative of CNS disturbances or overstimulation. Mortality and morbidity rates are high and there is no specific antidote. We present an uncommon presentation of endosulfan poisoning in a 32-year-old male with high anion gap severe refractory metabolic acidosis. The patient was treated with continuous renal replacement therapy and was salvaged. Till date, there is no case report from India for endosulfan poisoning with severe metabolic acidosis and hypotension. Through this case report, we emphasize the role of continuous renal replacement therapy as a rescue therapy for endosulfan poisoning with severe refractory metabolic acidosis and hypotension, even though it is a non dialyzable poison.

Clonidine as an analgesic adjuvant to continuous paravertebral bupivacaine for post-thoracotomy pain.

We prospectively evaluated the effect of clonidine as an adjuvant to bupivacaine for continuous paravertebral intercostal nerve block, measuring pain and sedation scores and pulmonary function tests. Thirty patients scheduled to undergo thoracotomy were randomized to receive either a bolus of 0.125% bupivacaine 2 mg/kg (group BUP) or 0.125% bupivacaine 2 mg/kg with clonidine 2 microg/kg (group BUP+CLO), followed by an infusion of 0.125% bupivacaine at 0.5 mg/kg/h, or 0.125% bupivacaine at 0.5 mg/kg/h with clonidine at 2 microg/kg/h, in respective groups, through a paravertebral intercostal catheter. Haemodynamic parameters, pain and sedation scores and pulmonary function tests were recorded at 6, 12, 24 and 48 hours after arrival in postoperative care unit. There were significantly lower pain scores at rest and on coughing in group BUP+CLO compared with group BUP (P <0.01). Multiple comparisons revealed a significant reduction in pain score at each time point (P<0.01), except at 12h to 24h, in group BUP+CLO. Sedation scores were significantly higher in group BUP+CLO compared with group BUP at each time point (all P<0.01). There was a linear effect of time on sedation score in group BUP whereas in group BUP+CLO, the effect was quadratic. Patients in the clonidine group had a higher incidence of hypotension (P < 0.01). There was no significant difference in pulmonary function between the groups. We conclude that using clonidine as an adjunct to bupivacaine for continuous paravertebral intercostal nerve block improves pain relief after thoracotomy, but hypotension and sedation are adverse effects interfering with its clinical application.

Role of reactive oxygen species in IL-1 beta-stimulated sustained ERK activation and MMP-9 induction.

We have recently demonstrated that interleukin-1 beta (IL-1 beta) stimulates matrix metalloproteinase-9 (MMP-9) induction. In this study we have investigated the roles of superoxide and extracellular signal-regulated kinase (ERK) activation in MMP-9 induction following exposure to IL-1 beta. IL-1 beta stimulated biphasic ERK activation in vascular smooth muscle (VSM) cells, a transient activation that reached a maximum at 15 min and declined to baseline levels within 1 h, and a second phase of sustained ERK activation lasting up to 8 h. To determine the role of ERK in IL-1 beta-stimulated MMP-9 induction, we treated cells with the specific ERK pathway inhibitor PD-98059 at different time intervals after IL-1 beta stimulation. Addition of PD-98059 up to 4 h after IL-1 beta stimulation significantly inhibited MMP-9 induction, suggesting a role for sustained ERK activation in MMP-9 induction. IL-1 beta treatment stimulated superoxide production in VSM cells that was inhibited by pretreatment of cells with the superoxide scavenger N-acetyl-L-cysteine (NAC) and also by overexpression of the human manganese superoxide dismutase (MnSOD) gene. Treatment of VSM cells with NAC selectively inhibited the sustained phase of ERK activation without influencing the transient phase, suggesting a role for reactive oxygen species in sustained ERK activation. In addition, both NAC treatment and MnSOD overexpression significantly inhibited IL-1 beta-stimulated MMP-9 induction (P < 0.05). The results demonstrate that IL-1 beta-dependent MMP-9 induction is mediated by superoxide-stimulated ERK activation.

Selected contribution: estrogen receptor-alpha gene transfer inhibits proliferation and NF-kappaB activation in VSM cells from female rats.

Epidemiological studies have demonstrated that hormone replacement therapy with estrogen (E2) or E2 plus progesterone in postmenopausal women decreases the age-associated risk of cardiovascular disease by 30-50%. Treatment of vascular smooth muscle (VSM) cells with physiological concentrations of E2 has been shown to inhibit growth factor-stimulated cell proliferation. In this study, we tested the hypothesis that E2 inhibits the age-associated increase in VSM cell proliferation by inhibiting nuclear factor (NF)-kappaB pathway. We investigated the effects of E2 treatment and adenovirus-mediated estrogen receptor (ER)-alpha gene transfer on cell proliferation and NF-kappaB activation using VSM cells cultured from 3-mo-old and 24-mo-old Fischer 344 female rats. Our results demonstrate that VSM cell proliferation was significantly increased (P < 0.05) in aged compared with young adult female rats. Treatment of VSM cells with physiological concentrations of E2 inhibited VSM cell proliferation, and this inhibition was significantly greater (P < 0.05) in cells from aged female rats compared with young adults. The inhibitory effects of E(2) on cell proliferation in aged female rats were significantly potentiated by overexpression of the human ER-alpha gene into VSM cells. Constitutive and interleukin (IL)-1beta-stimulated NF-kappaB activation was significantly greater (P < 0.05) in VSM cells from aged compared with young female rats. E2 treatment of VSM cells from aged female rats inhibited both constitutive and IL-1beta-stimulated NF-kappaB activation. ER-alpha gene transfer into VSM cells from aged female rats further augmented the inhibitory effects of E2. In conclusion, our data demonstrate that constitutive and IL-1beta-stimulated NF-kappaB activation is increased in VSM cells from aged female rats due to loss of E2 and this can be restored back to normal levels by ER-alpha gene transfer and E2 treatment. In addition, increased NF-kappaB signaling may be responsible for increased incidence of cardiovascular disease in postmenopausal females.

Mechanism of inhibition of matrix metalloproteinase-9 induction by NO in vascular smooth muscle cells.

Vascular smooth muscle (VSM) cell migration is a critical step in the development of a neointima after angioplasty. Matrix metalloproteinases (MMPs) degrade the basement membrane and extracellular matrix, facilitating VSM cell migration. Recently, we demonstrated that nitric oxide (NO) inhibits interleukin-1 beta (IL-1 beta)-stimulated MMP-9 induction in rat aortic VSM cells. In this study, we examined the hypothesis that NO inhibits MMP-9 induction by attenuating superoxide generation and extracellular signal-regulated kinase (ERK) activation. Stimulation of VSM cells with IL-1 beta significantly (P < 0.05) increased superoxide production, ERK activation, and MMP-9 induction. Pretreatment of VSM cells with the NO donor DETA NONOate significantly (P < 0.05) decreased IL-1 beta-stimulated superoxide generation. In addition, pretreatment of VSM cells with a specific ERK pathway inhibitor, PD-98059, or DETA NONOate inhibited IL-1 beta-stimulated ERK activation and MMP-9 induction. Direct exposure of VSM cells to increased superoxide levels by treatment with xanthine/xanthine oxidase increased ERK activation and MMP-9 induction, whereas pretreatment of cells with PD-98059 significantly (P < 0.05) inhibited xanthine/xanthine oxidase-stimulated ERK activation and MMP-9 induction. We conclude that NO inhibits IL-1 beta-stimulated MMP-9 induction by inhibiting superoxide generation and subsequent ERK activation.

Radical mediated ring opening of 1,2-cyclopropanated-D-glycal: unusual formation of S-methylglycosyl-S-methylthiocarbonate.

Tri-n-butyltin hydride mediated ring opening of 1,2-cyclo- propanated-D-glycals led to the formation of 1-C-methyl 2,3-unsaturated sugars. However, corresponding catalytic version provided an unusual S-methylglycosyl-S-methyldithiocarbonate derivative whose mechanism of formation has been proposed.

Synthesis of oligosaccharides of motifs D and E of arabinogalactan present in Mycobacterium tuberculosis.

Syntheses of the ethyl glycosides of 5-O-(beta-D-galactofuranosyl)-beta-D-galactofuranose and 5-O-(alpha-D-arabinofuranosyl)-6-O-(beta-D-galactofuranosyl)-beta-D-galactofuranose present in motifs D and E of Mycobacterium tuberculosis arabinogalactan, respectively, have been presented. The pentenyl-mediated O-glycosylation reaction was utilized to obtain the disaccharide of motif D. The first coupling reaction to prepare the inner disaccharide portion of motif E was accomplished by trichloroacetamidate method while the installation of the terminal sugar by pentenyl glycosylation approach was successful.