Sustained release of alpha-methylacyl-CoA racemase (AMACR) antibody-conjugated and free doxorubicin from silica nanoparticles for prostate cancer cell growth inhibition.

This article presents silica nanoparticles for the sustained release of AMACR antibody-conjugated and free doxorubicin (DOX) for the inhibition of prostate cancer cell growth. Inorganic MCM-41 silica nanoparticles were synthesized, functionalized with phenylboronic acid groups (MCM-B), and capped with dextran (MCM-B-D). The nanoparticles were then characterized using Fourier-transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, zeta potential analysis, nitrogen sorption, X-ray diffraction, and thermogravimetric analysis, before exploring their potential for drug loading and controlled drug release. This was done using a model prostate cancer drug, DOX, and a targeted prostate cancer drug, α-Methyl Acyl-CoA racemase (AMACR) antibody-conjugated DOX, which attaches specifically to AMACR proteins that are overexpressed on the surfaces of prostate cancer cells. The kinetics of sustained drug release over 30 days was then studied using zeroth order, first order, second order, Higuchi, and the Korsmeyer-Peppas models, while the thermodynamics of drug release was elucidated by determining the entropy and enthalpy changes. The flux of the released DOX was also simulated using the COMSOL Multiphysics software package. Generally, the AMACR antibody-conjugated DOX drug-loaded nanoparticles were more effective than the free DOX drug-loaded formulations in inhibiting the growth of prostate cancer cells in vitro over a 96 h period. The implications of the results are then discussed for the development of drug-eluting structures for the localized and targeted treatment of prostate cancer.

Prevalence of Pulmonary Hypertension in Chronic Kidney Disease.

Pulmonary hypertension is a common comorbidity in patients with chronic kidney disease and end-stage renal disease(CKD). The presence of pulmonary hypertension is associated with increased risk of hospitalization and mortality in patients with CKD. Review of literature showed that in one study, pulmonary hypertension was found in 40% of patients with end stage renal disease on chronic hemodialysis therapy via arteriovenous access. The presence of CKD was associated with 1.4-fold increased risk of having pulmonary hypertension after adjusting for other independent risk factors for CKD. Preventing pulmonary hypertension in this population is crucial because even kidney transplantation may not reverse the high mortality associated with established pulmonary hypertension. MATERIAL: Place of study- Rajendra Institute of Medical Sciences, Ranchi. Design of study- Observational and prospective single centered study. Duration of study-18 months. Sample size-100 CKD patients admitted to department of medicine, RIMS, Ranchi. Study population-100 CKD patients meeting our inclusion criteria, admitted in the department of medicine, Rajendra Institute of Medical Sciences, Ranchi, between 1st January 2020 and 30th June 2021. INCLUSION CRITERIA: Renal function was determined by estimated glomerular filtration rate. Only patients with stage 3 or worse CKD were included. EXCLUSION CRITERIA: 1. Those patients having stage 2 or less kidney disease were excluded. 2. Patients with congenital heart disease, chronic thromboembolic disease, acute myocardial infarction and previous lung disease or cardiac transplantation were excluded. Data was collected by oral questionnaire, relevant investigations and by doing 2D- ECHO and data was analyzed by using IBM SPSS Statistics software. OBSERVATION: Prevalence of pulmonary hypertension in the study group was 16%. Prevalence of pulmonary hypertension was more in stage 5 CKD patients (26.19%) and the difference in prevalence of pulmonary hypertension in different stages of CKD was statistically significant(p value-0.008). Prevalence of pulmonary hypertension was more in patients on hemodialysis (27.78%) compared to those not on hemodialysis (9.37%). Pulmonary hypertension was present in 13.85% males and 20% of females, there was no statistically significant difference (p value-.428). No significant difference was found in prevalence of pulmonary hypertension between diabetic and non- diabetic patients and hypertensive and normotensive patients. CONCLUSION: Prevalence of pulmonary hypertension was more in stage 5 CKD patients and patients on hemodialysis. There was positive correlation between high serum creatinine, high serum phosphorus, lower hemoglobin, lower serum calcium and pulmonary hypertension in CKD patients. There was no significant difference in prevalence of pulmonary hypertension in male and female patients.

Current Trends of Using Antimicrobials at Obstetrics and Gynaecology Department in a Tertiary Care Hospital.

This cross-sectional descriptive study was done to analyse the current trends of using antimicrobials in various surgical procedures at Obstetrics and Gynaecology department in Mymensingh Medical College Hospital, Mymensingh from July 2014 to June 2015. Among 300 postoperative obstetrics and gynaecological surgery cases, samples were selected as non-random purposive selection method where pattern of using antimicrobials were analysed by SPSS method 20.1 versions. The incidence of antimicrobial resistance is on continued rise with a threat to return to the pre-antibiotic era. This has led to emergence of such bacterial infections which are essentially untreatable by the current armamentarium of available treatment options. Now-a-days variation of choosing antibiotic are quietly accepted in Obstetrics and Gynaecology department as prophylaxis purpose to control life threatening conditions such as postoperative wound infection, septicaemia, urinary tract infection etc. The data analysis revealed that among 300 obstetrical and gynaecological surgeries, Nitroimidazoles (93.33%), Cephalosporins (91%) and Aminoglycosides (59%) group were most commonly used antimicrobials in both obstetrics and gynaecological surgeries. Metronidazole (93.33%), Ceftriaxone (68.66%), Gentamicin (60.33%), Cefuroxime (48%), Flucloxacillin (42%), Cefixime (27%) were the most commonly used antimicrobials at obstetrics and gynaecology department. Combination of Ceftriaxone, Metronidazole and Gentamicin (37.66%), Ceftriaxone and Metronidazole (25.33%), Cefuroxime, Metronidazole and Gentamicin (16%), Ciprofloxacin, Metronidazole and Gentamicin (5.33%) were most commonly used antimicrobials postoperatively. Total mean duration of antimicrobial therapy was 10.45 days. Antibiotics are useful in prevention of infection. But indiscriminately use of antibiotics without any guideline may lead to antimicrobial resistance. So, antimicrobial surveillance committee should be formed by hospital authority to know the local using pattern of antibiotics.

Meta-Emotion Philosophy Among Asian Indian Immigrant Mothers in the United States.

We explored the meta-emotion philosophies of Indian immigrant mothers living in the Midwest region of the United States to expand the scarce literature on emotion socialization in diverse families. A total of 15 mothers of teen and preteen children participated in a meta-emotion interview, in which they were asked about their own and their children's experiences of anger, sadness, and fear. We analyzed interview responses through an open-ended phenomenological approach and found the following major themes: familial context of emotions, subtle communication of emotions, and an overarching philosophy centering on inevitability of negative emotions and the importance of moving on. Mothers differed in how well they believed that they could move on. Overall, the present findings demonstrate the role culture plays in emotional experiences of immigrant mothers and serve as a reminder that theories based on European American families might have limited applicability to other cultural and ethnic groups.

Fabrication of a novel biomaterial with enhanced mechanical and conducting properties.

Conducting polymers have the combined advantages of metal conductivity with ease in processing and biocompatibility; making them extremely versatile for biosensor and tissue engineering applications. However, the inherent brittle property of conducting polymers limits their direct use in such applications which generally warrant soft and flexible material responses. Addition of fillers increases the material compliance, but is achieved at the cost of reduced electrical conductivity. To retain suitable conductivity without compromising the mechanical properties, we fabricate an electroactive blend (dPEDOT) using low grade PEDOT:PSS as the base conducting polymer with polyvinyl alcohol as filler and glycerol as a dopant. Bulk dPEDOT films show a thermally stable response till 110 °C with over seven fold increase in room temperature conductivity as compared to 0.002 S cm-1 for pristine PEDOT:PSS. We characterize the nonlinear stress-strain response of dPEDOT, well described using a Mooney-Rivlin hyperelastic model, and report elastomer-like moduli with ductility ∼ fives times its original length. Dynamic mechanical analysis shows constant storage moduli over a large range of frequencies with corresponding linear increase in tan(δ). We relate the enhanced performance of dPEDOT with the underlying structural constituents using FTIR and AFM microscopy. These data demonstrate specific interactions between individual components of dPEDOT, and their effect on surface topography and material properties. Finally, we show biocompatibility of dPEDOT using fibroblasts that have comparable cell morphologies and viability as the control, which make dPEDOT attractive as a biomaterial.

[Physiological parameters of breathing and the impact of non-invasive ventilation (NIV) on patients with amyotrophic lateral sclerosis (ALS)]. / Physiologische Atmungsparameter und der Effekt der nicht invasiven Beatmung (NIV) bei Patienten mit amyotropher Lateralsklerose (ALS).

BACKGROUND: Amyotrophic lateral sclerosis (ALS), as a consequence of the progressive failure of respiratory muscles, often causes chronic ventilatory failure (CVF), indicated by hypercapnia. This study analyses the physiological parameters of breathing in patients with ALS over time and the variables which influence survival time. METHODS: In this observational study we analysed the data of physiological parameters (respiratory function, blood gas levels and breathing during sleep), as well as survival rate (according to Kaplan-Meier) of all 85 ALS patients who stayed in our hospital during the period of 1st January 2003 until 31st December 2007. After ALS had been diagnosed, all patients ran through standardised pneumological diagnostics during the observation period, this procedure was repeated every 3-6 months. If hypercapnia (carbon dioxide tension pCO(2) > 45 mm Hg) was detected, non-invasive ventilation (NIV) was indicated and offered to the respective patients. RESULTS: In the course of the observation, the parameters of respiratory function IVC (inspiratory vital capacity) and FEV1 (forced expiratory volume after 1 second) have shown a significant reduction by 14-15% per year. Half of the patients died within 3.1 years after ALS had been diagnosed. IVC and FEV1 had no impact on the survival time. In contrast, pCO(2) correlates negatively with the survival time. The period between diagnosis of ALS and manifestation of hypercapnia is about 1.9 +/- 2.4 years. In spite of a clear indication, some of the patients did not comply with NIV or did not accept it (19 patients, 22%). Twenty-eight patients (33%) started NIV with a good compliance. The survival rate of patients with NIV was 1.27 years on average--after the initial measurement of hypercapnia. The survival time of hypercapnic patients without NIV was only 0.12 years. CONCLUSIONS: Hypercapnia has a significant impact on the prognosis for ALS patients. In the case of CVF (hypercapnia), the survival time of ALS patients is significantly reduced. NIV is able to significantly increase the survival time of ALS patients with hypercapnia.

[Frequency and influence of nosocomial pathogens on weaning outcome and in-hospital mortality in mechanically ventilated patients in a regional weaning centre in comparison of the years 2002 and 2006]. / Häufigkeit und Bedeutung von Bakterienisolaten bei langzeitbeatmeten Patienten und deren Einfluss auf das Weaning-Outcome und die Hospital-Letalität in einem überregionalen Weaningzentrum im Verlauf.

BACKGROUND: Patients with nosocomial infections in the intensive care unit (ICU) seem to have a poor prognosis. In this retrospective cohort study we investigated the relationship between weaning outcome, in-hospital mortality and the microbiological proof of nosocomial pathogens from secretions in mechanically ventilated patients in the years 2002 and 2006. PATIENTS AND METHODS: 311 patients with long term (> 14 days) invasive (tube or tracheostomy) mechanical ventilation (MV) were enrolled in to the study when they had failed at least two weaning attempts prior to transfer. Microbiological proof of nosocomial pathogens from secretions sampled by the bronchoscope and an X-ray of the chest on admission day (in the transferring ICU and in our ICU) was collected from all patients. RESULTS: There was a significant decline of the weaning success rate between 2002 and 2006 (p = 0.001). The In-hospital mortality was higher in 2006 (p = 0.03). The microbiological proof of nosocomial pathogens had no influence on the weanability (exception: MRSA patients in 2002). In both years, patients with infiltrates on X-ray of the chest showed no increased mortality. But in 2006 it took longer to liberate these patients from invasive MV. In 2002 microbiological proof of pathogens was related to higher in-hospital mortality. In 2006, there was no difference concerning mortality in both groups. CONCLUSIONS: Proof of nosocomial pathogens and infiltrates had no influence on the weanability of long-term mechanically ventilated patients. For in-hospital mortality, the results are contradictory.

[Follow-up examination and probatory CPAP therapy of obstructive sleep apnoea increase the long-term compliance]. / Poststationäre Nachsorge und probatorische CPAP-Therapie schlafbezogener obstruktiver Atemstörungen steigern die Langzeitcompliance.

INTRODUCTION: Since the implementation of CPAP therapy in the treatment of obstructive sleep apnoea in the 1980 s researchers have been looking for predictors and possibilities to improve long-term compliance. In a prospective randomised trial we examined the influence of a follow-up examination two weeks after the start of probatory CPAP therapy compared to immediate prescription of the CPAP device. METHODS: 249 new patients with a newly diagnosed obstructive sleep apnoea (OSA) started with a CPAP therapy. These patients were prospectively randomised depending on the dates of admission (even/uneven). The CPAP device for the first group was immediately prescribed. Patients of the second group were seen in our sleep laboratory ambulance after a probatory usage of the CPAP therapy over a period of fourteen days. After 433 +/- 138 days we measured the compliance by reading off the operating hours counter. In order to collect these data all patients received written simple instructions how to read off the operating hours counter. They sent back the results via a prepaid return envelope. In addition, we obtained the information as to whether a hot water bath humidifier was used. RESULTS: 171 of the initially 249 patients sent back the evaluation form. The randomisation of the groups was successful concerning: age, sex as well as the apnoea-hypopnoea index before and under CPAP therapy. 226 patients were treated with the fix-CPAP mode (mean pressure 8.1 +/- 1.8 cm H(2)O), 23 patients received auto CPAP therapy. The patients with a probatory CPAP therapy and follow-up examination showed a significantly (p = 0.01) better compliance of nocturnal CPAP use with 4.5 +/- 1.8 h/night versus those who had their CPAP device immediately prescribed with a use of 3.8 +/- 2.1 h/night. The percentage of patients with a use of CPAP more than 4 h/night was significantly higher in the group with probatory therapy (66.3 % vs. 45.6 %; p = 0.008). Patients with probatory CPAP therapy made more use of humidifiers than the immediate prescription group; however, the use of a humidifier did not have any significant influence on the long-term compliance (p = 0.58). CONCLUSION: The combination of probatory CPAP therapy and follow-up examination increases the long-term compliance significantly in the treatment of obstructive sleep apnoea.

The use of APACHE II prognostic system in difficult-to-wean patients after long-term mechanical ventilation.

BACKGROUND AND OBJECTIVE: To examine the calibration of the prognostic system Acute Physiology and Chronic Health Evaluation Score (APACHE II) regarding hospital mortality and predicting weaning outcome after long-term mechanical ventilation of the lungs. METHODS: Prospective observational cohort study performed in a respiratory intensive care unit including 246 patients whose lungs were ventilated for 42.1+/-37.8 (median 30) days in the referring hospital. APACHE II (24 h after admission to our respiratory intensive care unit) and the cause of respiratory failure, underlying disease, prior duration of mechanical ventilation and gender were recorded. The predictive power was evaluated with sensitivity and specificity for different cut-off points and summarized in a receiver operating characteristic curve. RESULTS: No difference was found between survivors (APACHE II 16.0+/-4.3) and non-survivors (APACHE II 16.9+/-5.1). In a mean time of 8.0+/-10.3 days, 146 patients (59.3%) were successfully weaned (APACHE II 15.2+/-3.5). One-hundred patients (40.7%) were considered unweanable (APACHE II 17.7+/-5.3). Recalibration of APACHE II to predict weaning failure was possible, resulting in an area under the receiver operating characteristic curve (AUC) of 0.638. Furthermore the AUC improved to 0.723 by changing the weights of selected APACHE items and introducing external factors. Diagnostic accuracy fell from group with mechanical ventilation < or =25 days (AUC 0.770) to group with mechanical ventilation >50 days (AUC 0.517). CONCLUSIONS: APACHE II did not predict hospital mortality after long-term mechanical ventilation of the lungs. Not the original APACHE II but a recalibrated and adapted APACHE II can be useful to predict weaning outcome in patients with less than 25 days of prior lung ventilation.

Survival of mechanically ventilated patients admitted to a specialised weaning centre.

OBJECTIVE: Hospital mortality and survival rates of long-term ventilated patients.DESIGN. Retrospective cohort study. SETTING: Specialised national weaning centre. INTERVENTION: Protocol-directed liberation from ventilator. PATIENTS: Four hundred three of 640 patients with prolonged mechanical ventilation (MV) who were admitted to our respiratory intensive care unit (RICU) were studied. MV lasted longer than 2 weeks and patients had failed more than two weaning trials in the referring ICUs. The majority of patients (59.3%) had chronic obstructive pulmonary disease (COPD). RESULTS: After a mean duration of 41 days of MV prior to transfer, 68% of patients were liberated from the ventilator. In total, 98 of 403 patients (24.3%) died during the stay in our hospital, 305 patients (75.7%) were discharged. Compared to the non-survivors, the survivors were characterised by younger age, longer length of stay in our RICU, lower severity of illness scores at admission, fewer cardiac illnesses and a higher rate of weaning success. In 31.5% of the discharged patients non-invasive MV (NIV) was initiated during the stay at our unit. We gathered follow-up data on 293 patients (96.1%). Post-discharge survival rates were 67.6% at 3 months, 49.4% at 1 year and 38.1% at 3 years. Length of survival was significantly dependent on age, weaning success and main diagnosis (i.e., prognosis in COPD is worse compared to thoracic restriction, neuromuscular disease and others) in the multivariate analysis. CONCLUSIONS: Difficult-to-wean patients have a high hospital mortality rate and poor long-term prognosis. Age, main diagnosis, severity of illness, weaning success and institution of NIV predict survival.

[Positive pressure ventilation in Cheyne-Stokes respiration]. / Positivdruckverfahren bei Cheyne-Stokes-Atmung infolge chronischer Herzerkrankung.

Cheyne-Stokes respiration (CSR) is found in patients with chronic left ventricular failure and associated with a reduced prognosis. Continuous positive airway pressure (CPAP) improves the survival rate. In this retrospective study we report on the effect of different positive pressure ventilation modes in CSR. The observation period lasted from 1995 - 1999. Inclusion criteria was CSR with a respiratory disturbance index > 10/h whereas > 50 % of the events had to be central and/or mixed. In each patient a 4 week lasting intervention with each of CPAP, Bilevel CPAP in spontan mode (i.e. BiPAP S or BiPAP ST) and BiPAP in controlled mode (i.e. BiPAP T) was performed. Responder were defined by subjective and objective criteria. In total 41 males were included. Responder were distributed as follows: CPAP: n = 13 patients (31.7 %), BiPAP S/ST: n = 9 patients (22.0 %) and BiPAP T: n = 12 patients (29.3 %). In total 7 from 41 patients (17.1 %) rejected a long-term treatment with positive pressure ventilation. The majority of patients with CSR responded to CPAP and BiPAP S/ST mode. Compared to the other responder groups the best quality was reached with BiPAP T. However the latter was performed only by 29 % of the population.

Sexuality in patients with noninvasive mechanical ventilation due to chronic respiratory failure.

In patients with chronic respiratory failure (CRF) noninvasive mechanical ventilation (NMV) improves quality of life. We studied some basic issues concerning sexuality in patients with NMV. In 383 patients with NMV for CRF (age, > 40 yr) physiologic data (lung function, blood gases, and exercise) were taken from within the 6 mo period before enrollment. The questionnaire was focused on sexuality after initiation of NMV. Of the patients, 54.3% sent back the questionnaire. NMV was used for 41.1 +/- 27.0 mo. A total of 34.1% of patients were sexually active. Compared with patients receiving NMV, control persons had a higher rate of sexual activity (84%, p < 0.0001) and masturbation rate (13 versus 40%). Sexually active patients had greater VC (2.1 versus 1.8 L), higher FEV(1) (1.4 versus 1.1 L), higher Pa(O(2)) at rest (64.0 versus 60.4 mm Hg), a higher maximal work load (72.0 versus 58.8 W), were younger, and most of them were married or had sexual partners. Changes in sexual activity after NMV initiation were reported to be as follows: "Nothing changed," 46.3%; "less active," 35.8%; "more active," 12.6%; and "fantasy increased," 10.5%. Increased sexual fantasy predominated in men. "Sexually active" patients with NMV had sexual intercourse 5.4 +/- 4.8 times per month. Sexuality in patients receiving NMV for CRF is markedly reduced compared with normal subjects. In half of the patients, sexual activity is influenced by initiation of NMV.

["Epidemiology" of the value of orally administered morphine as therapy of severe pulmonary emphysema of the pink-puffer type]. / Eine "Epidemiologie" zum Stellenwert von oral appliziertem Morphium als Therapieform des schwergradigen Lungenemphysems vom Pink-Puffer-Typ.

OBJECTIVES: Patients with severe emphysema from pink puffer type (PPT) are symptom-limited due to dyspnea even at low level of activity. In this study we investigated the clinical effect of oral morphine in this group of patients. MATERIALS AND METHODS: Based on the analysis of medical records (n = 456 patients) and a currently answered questionnaire (n = 205 patients) we analyzed data of all patients with emphysema being treated from 1995-1999. RESULTS: Dyspnea improved during the adaptation period on the ward in 59.4% of the whole population being treated with morphine and in 67.7% of the analyzed patients after discharge. Before discharge the treatment with morphine was finished by 38.9% of the population. In the group of long-term survivors approximately 50% of patients continued the treatment. In total, about 10% of the collective finished the treatment due to intolerable side effects. In the 5-year observation period morphine has been increasingly applied in an earlier stage of the disease. CONCLUSION: In patients with severe emphysema from pink puffer type a trial with morphine is justified. In particular the beneficial effect on dyspnea in the responder group and the acceptable rate of side effects underline this strategy.

The influence of abiotic factors on the onset and cessation of activity of semi-free Callithrix jacchus.

The influence of abiotic environmental factors on the period of activity of a single group of South American common marmosets (Callithrix jacchus, Callitrichidae, Primates) was investigated under semi-free conditions. A group of eight members had a territory consisting of a heated wooden hut with a veranda, surrounded by an open area with a few trees (ca. 3.5 m high) and three runways made out of roofing slats, on which feeding places and sleeping boxes were fixed. The food supply was held constant throughout the observation period with respect to amount, composition and spatial distribution. From July to November 1995, the times of the onset and cessation of activity were determined using a video camera. An electronic weather station recorded the temperature, humidity, air pressure, wind speed, wind direction, precipitation, and light intensity at intervals of 5 min. There was a linear correlation between day light length and the length of the period of activity over a day length of 10 to 14 hr. With shorter day lengths, the marmosets were also active during the twilight, whereas with longer day lengths a sleep phase during the late morning was introduced. Ambient temperature and humidity had also an effect on the time when activity began or ceased. Callithrix jacchus has one of the longest activity periods within the Callitrichidae. The time of sunrise or sunset, temperature, and humidity accounted for 66.2% of the variation in the time when activity began and 75.5% of the variance in the cessation of activity of the study group within the multivariate model. The results from the present study add to the indications that in the Callitrichidae there is a strong selection pressure for the highest possible energy saving during the comparatively long phase of inactivity.