Antidepressant prescription patterns and polypharmacy in outpatient psychiatry: a cross-sectional study.

Background and aim: Prescription patterns of antidepressants have changed over the years with a shift towards newer antidepressants with better tolerability and safety. Polypharmacy is common in psychiatry settings. The study aimed to evaluate the antidepressant drug prescription pattern and polypharmacy in a psychiatry outpatient setting. Investigations: This prospective observational study was conducted in a psychiatric outpatient clinic. The medication use data of eligible patients were collected. In addition, the rationale of antidepressant medication prescription, the defined daily dosage (DDD), the prescribed daily dose (PDD), and the PDD to DDD ratio were assessed. The assessment of prescription polypharmacy was conducted utilizing the framework provided by the National Association of State Mental Health Program Directors. Results: Data from 131 patients was analyzed. Major depressive disorder (32.8%) was the most common disorder for which antidepressants were prescribed. The majority, 91 (69.4%), received monotherapy. Selective serotonin reuptake inhibitors were the most frequently prescribed drugs in 69 (52.7%). Mirtazapine was the most frequently 32(24.4%) prescribed drug. Escitalopram and mirtazapine were the most commonly prescribed combination therapy (4.6%). Antipsychotic medications (37.4%) were the most widely co-prescribed medications, along with antidepressants. The PDD to DDD ratio was less than 1 for mirtazapine and imipramine; they were ≥1 for others. Psychiatric polypharmacy was documented in 87.1% of prescriptions. The total polypharmacy was not significantly (p>0.05) associated with demographic, illness, and treatment-related variables. Conclusion: Selective serotonin reuptake inhibitors were the most commonly prescribed antidepressants, monotherapy, and combination therapy. A substantial amount of patients received concomitant administration of antidepressants or psychotropic drugs, warranting careful monitoring.

Morphology of human fetal enteric neurons: A comparative study of different segments of the colon.

OBJECTIVES: The Enteric Nervous System (ENS) present in the wall of the gut is currently being explored because of its influence on the gut and beyond. In this context, the morphology of developing ENS has not been completely understood in humans due to lack of adequate literature. The aim of the present study was to observe the morphology of the enteric neurons in the human fetal colon and compare the findings in ascending colon a midgut derivative and descending colon a hindgut derivative at various weeks of gestation (WG). MATERIAL AND METHODS: Tissue samples from 15 aborted fetuses (11 WG to 2 months postnatal) were processed for Cresyl violet, H & E staining, and NADPH Diaphorase histochemistry. The morphometric analysis was done by calculating the neuronal number density and neuronal fractional area. The Student t-test; Mann-Whitney test and Wilcoxon signed-rank test were used to analyze the data. RESULTS: The muscularis externa with two distinct layers was visible as early as 13 WG and the muscularis mucosae was first observed at 18 WG. The size of the myenteric neurons appeared to be larger with increasing weeks of gestation suggesting a process of neuronal maturation. The neuronal number density and neuronal fractional area seemed to be reduced with advancing fetal age. There was no marked difference between the ascending and sigmoid colon. At 23 and 26 WG, a mature pattern of nitrergic innervation was observed. CONCLUSION: This study is done on human fetal tissue samples unlike previous studies on animal samples to comprehend the morphology of developing ENS. It will aid in understanding the effect of ENS on various neurological disorders.

Artificial Intelligence-assisted chest X-ray assessment scheme for COVID-19.

OBJECTIVES: To study whether a trained convolutional neural network (CNN) can be of assistance to radiologists in differentiating Coronavirus disease (COVID)-positive from COVID-negative patients using chest X-ray (CXR) through an ambispective clinical study. To identify subgroups of patients where artificial intelligence (AI) can be of particular value and analyse what imaging features may have contributed to the performance of AI by means of visualisation techniques. METHODS: CXR of 487 patients were classified into [4] categories-normal, classical COVID, indeterminate, and non-COVID by consensus opinion of 2 radiologists. CXR which were classified as "normal" and "indeterminate" were then subjected to analysis by AI, and final categorisation provided as guided by prediction of the network. Precision and recall of the radiologist alone and radiologist assisted by AI were calculated in comparison to reverse transcriptase-polymerase chain reaction (RT-PCR) as the gold standard. Attention maps of the CNN were analysed to understand regions in the CXR important to the AI algorithm in making a prediction. RESULTS: The precision of radiologists improved from 65.9 to 81.9% and recall improved from 17.5 to 71.75 when assistance with AI was provided. AI showed 92% accuracy in classifying "normal" CXR into COVID or non-COVID. Analysis of attention maps revealed attention on the cardiac shadow in these "normal" radiographs. CONCLUSION: This study shows how deployment of an AI algorithm can complement a human expert in the determination of COVID status. Analysis of the detected features suggests possible subtle cardiac changes, laying ground for further investigative studies into possible cardiac changes. KEY POINTS: • Through an ambispective clinical study, we show how assistance with an AI algorithm can improve recall (sensitivity) and precision (positive predictive value) of radiologists in assessing CXR for possible COVID in comparison to RT-PCR. • We show that AI achieves the best results in images classified as "normal" by radiologists. We conjecture that possible subtle cardiac in the CXR, imperceptible to the human eye, may have contributed to this prediction. • The reported results may pave the way for a human computer collaboration whereby the expert with some help from the AI algorithm achieves higher accuracy in predicting COVID status on CXR than previously thought possible when considering either alone.

Short-Term Effects of Strengthening Exercises of the Lower Limb Rehabilitation Protocol on Pain, Stiffness, Physical Function, and Body Mass Index among Knee Osteoarthritis Participants Who Were Overweight or Obese: A Clinical Trial.

BACKGROUND: Osteoarthritis (OA) of the knee is defined as a progressive disease of the synovial joints and is characterized by wear and tear of the cartilage and underlying bone. This study aimed to determine the short-term effects of the lower limb rehabilitation protocol (LLRP) on pain, stiffness, physical function, and body mass index (BMI) among knee OA participants who were overweight or obese. Methodology. A single-blinded randomized controlled trial of one-month duration was conducted at Rehmatul-Lil-Alameen Postgraduate Institute, Lahore, Pakistan. Fifty overweight or obese participants with knee OA were randomly divided into two groups by a computer-generated number. Participants in the rehabilitation protocol group (RPG) were provided with leaflets explaining the strengthening exercises of the LLRP and instruction of daily care (IDC), while the participants in the control group (CG) were provided with leaflets explaining the IDC only for a duration of four weeks. The primary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for pain, stiffness, and physical function. The secondary outcome measures were BMI, exercise adherence, and patients' satisfaction assessed by using the numeric rating scale ranging from 0 to 10. The paired-sample t-test was used to analyze the differences within groups from baseline to posttest evaluations. The analysis of variance 2 × 2 factor was used to analyze the differences in BMI, knee pain, stiffness, and physical function between the groups. RESULTS: Participants in the RPG and CG reported a statistically significant reduction in knee pain and stiffness (p ≤ 0.05) within the group. The reduction in the scores of knee pain was higher in participants in the RPG than that in participants in the CG (p=0.001). Additionally, participants in the RPG reported greater satisfaction (p=0.001) and higher self-reported exercise adherence (p=0.010) and coordinator-reported exercise adherence (p=0.046) than the participants in the CG. CONCLUSION: Short-term effects of the LLRP appear to reduce knee pain and stiffness only, but not physical function and BMI.

Morphology of enteric glia in colorectal carcinoma: A comparative study of tumor site and its proximal normal margin.

OBJECTIVE: Colorectal carcinoma (CRC) is the third most common cancer in the world and fifth most common cancer in India. To understand the extent of perineural invasion (PNI) in CRC it is essential to study the morphology of enteric glial cells (EGCs). The aim of the study was to analyze the numerical density of EGCs and area of myenteric ganglia (MG) in the colonic tissue samples collected from CRC patients. MATERIAL AND METHODS: Fifteen intraoperative tissue specimens were collected from the tumor site and 2cm proximal to the upper extent of tumor. The samples were divided into four groups: group 1 (n=15): proximal tumor free colonic tissue; group 2 (n=3): well-differentiated; group 3 (n=8): moderately differentiated; group 4 (n=4): poorly differentiated adenocarcinoma. After processing the tissues were subjected to hematoxylin and eosin staining. The anti-S100ß and anti-GFAP antibodies were used to observe the EGCs. RESULTS: In the H&E stained sections the number of myenteric ganglia appeared to be decreasing with increasing grade of adenocarcinoma. Immunostaining showed significant decreasing pattern in the numerical density of EGCs per myenteric ganglion and mean area of myenteric ganglia in relation to the thickness of circular muscle, corresponding to the increasing grades of adenocarcinoma. The morphology of the EGCs remained unaltered in the colonic tissue adjacent to the tumor site. CONCLUSION: Significant loss of EGCs and neurodegeneration corresponded with the grade of tumor emphasizing on its prognostic value. The PNI was not seen in the clear margin proximal to the tumor site.

Abdominal muscle activation: An EMG study of the Sahrmann five-level core stability test.

BACKGROUND: Sahrmann five-level core stability test protocol has been used to evaluate the ability of the core muscles to stabilize the spine. However, validation studies on the Sahrmann protocol are limited. OBJECTIVE: The purpose of this study was to compare the different levels of Sahrmann five-level core stability (levels 1-5) on the muscle activity of rectus abdominis (RA), external oblique (EO), and transverse abdominis/internal oblique (TrA/IO). METHODS: Twenty-two asymptomatic male participants aged 21.3 6 ± 1 .59 years were recruited. Participants were instructed to perform maximum voluntary contraction (MVC) and five levels of Sahrmann five-level core stability test guided with a pressure biofeedback unit (PBU). The surface electromyography (EMG) data of each muscle during five levels of Sahrmann five-level core stability test were normalized as a percentage of MVC. RESULTS: Results showed significant differences in the normalized EMGs of RA [ χ 2 (4) = 64.80, p < 0 .001], EO [ χ 2 (4) = 58.11, p < 0 .001], and TrA/IO [ χ 2 (4) = 56.00, p < 0 .001] between the five levels of Sahrmann five-level core stability test. Post-hoc analysis revealed Sahrmann levels 5 and 3 have significantly higher abdominal EMG signals than levels 4, 2, and 1 ( p < 0 .001). CONCLUSION: In conclusion, the Sahrmann five-level core stability test differs according to the level of Sahrmann tests. Significantly higher abdominal muscle activities were observed during levels 3 and 5. Therefore, the classification exchange in levels 3 and 4 of the Sahrmann five-level core stability test should be reconsidered in the future.

Synthesis and thermal degradation studies of melamine formaldehyde resins.

Melamine formaldehyde (MF) resins have been synthesized at different reaction temperature and pH values. Different molar ratios of melamine and formaldehyde were used to synthesize the corresponding resins. The prepared resin samples were characterized by using molecular weight determination viscometry and thermogravimetric analysis (TGA). The maximum percentage of solid content (69.7%) was obtained at pH 8.5 and 75°C temperature. The molecular weight of MF resin was increased with an increase of melamine monomer concentration. The highest residual weight 14.125 wt.% was obtained with sample 10.

Fluoride Ingestion Induces Formation of Unusual Macromolecular Complexes in Gut Lumen Which Retard Absorption of Essential Minerals and Trace Elements by Chelation.

This study investigates the impact of chronic fluoride exposure on the absorption of essential minerals in the gut and explores the mechanisms underlying mineral deficiencies due to fluoride ingestion. Male Wistar rats were randomly assigned to three groups: group 1 (G-1) served as the control (non-fluoride exposed), while group 2 (G-2) and group 3 (G-3) received human equivalent doses (HED) of fluoride (50 and 100 ppm ad libitum, corresponding to 5 and 10 ppm in humans, respectively) for 75 days. Serum fluoride concentrations were measured, and the levels of essential minerals and trace elements in blood and stool were analyzed using ICP-MS. X-ray diffraction (XRD) analysis was performed on stool samples to identify chemical compounds. The chemical compounds and macromolecular complexes containing fluoride and essential minerals were identified and quantified using Match3 software. Results indicated that the blood concentrations of essential minerals were significantly lower (p ≤ 0.05) in the fluoride-exposed groups compared to the control, while excretion of essential elements in stool was significantly higher (p ≤ 0.05) in the fluoride-administered groups. XRD analysis revealed the formation of unusual macromolecular chemical complexes in the stool of fluoride-treated groups, with the types and concentrations of these compounds increasing with higher fluoride doses. The study concludes that fluoride in the stomach chelates minerals, reducing their absorption, and induces the formation of unusual high molecular weight macromolecular chelation complexes, which alter the chemical species in the gut and further impair the absorption of essential minerals.

Interrater and Intrarater Reliability of the Active Knee Extension (AKE) Test among Healthy Adults.

[Purpose] The purpose of this study was to determine the reliability of the active knee extension (AKE) test among healthy adults. [Subjects] Fourteen healthy participants (10 men and 4 women) volunteered and gave informed consent. [Methods] Two raters conducted AKE tests independently with the aid of a simple and inexpensive stabilizing apparatus. Each knee was measured twice, and the AKE test was repeated one week later. [Results] The interrater reliability intraclass correlation coefficients (ICC2,1) were 0.87 for the dominant knee and 0.81 for the nondominant knee. In addition, the intrarater (test-retest) reliability ICC3,1 values range between 0.78-0.97 and 0.75-0.84 for raters 1 and 2 respectively. The percentages of agreement within 10° for AKE measurements were 93% for the dominant knee and 79% for the nondominant knee. [Conclusion] The finding suggests the current AKE test showed excellent interrater and intrarater reliability for assessing hamstring flexibility in healthy adults.

Longitudinal surveillance of serum titanium ion levels in patients with indigenous 3D printed total temporomandibular joint replacement.

The purpose of this longitudinal study was to surveil the serum titanium ion levels at various time intervals in patients with indigenous 3D-printed total temporomandibular joint replacement (TMJ TJR). The study was conducted on 11 patients (male: 8; female: 3) who had undergone unilateral or bilateral TMJ TJR. Blood samples were drawn preoperatively (T0), 3 months (T1), 6 months (T2), and 1 year (T3) postoperatively. Data were analyzed and a p value of < 0.05 was considered statistically significant. The mean serum titanium ion levels at T0, T1, T2, and T3 was 9.34 ± 8.70 µg/L (mcg/L), 35.97 ± 20.27 mcg/L, 31.68 ± 17.03 mcg/L, and 47.91 ± 15.47 mcg/L respectively. The mean serum titanium ion levels increased significantly at T1 (p = 0.009), T2 (p = 0.032), and T3 (p = 0.00) interval. There was no significant difference between unilateral and bilateral groups. Serum titanium ion continued to show increased levels till the last follow-up of 1 year. These initial serum titanium ion levels increase is due to the initial wear phase of the prosthesis which manifests over 1 year. Further studies with large sample sizes and long-term follow-ups are required to see the deleterious effect if any on the TMJ TJR.

Cross-Sectional Study of Serum Metal Ions in Patients With Metal Implants in the Maxillofacial Region.

Purpose: The purpose of the present study was to measure the serum metal ion levels (titanium, cobalt, chromium) in patients who have metal implants in the maxillofacial region. Methods: The investigators implemented a cross sectional study on patients treated with procedures requiring metal implants for management of maxillofacial trauma, fixation for orthognathic surgery, and total temporomandibular joint replacement (TJR). Inductively coupled plasma mass spectrometry was used as an analytical method to detect metal ions in serum samples. Results: The study comprised of 50 patients who were divided into 4 groups- group I- total TJR (n = 18), group II- orthognathic (n = 8), group III- trauma (n = 8), and group IV- control (n = 16). The mean values of metal ions level were raised than the control group. Conclusion: The present study's results suggest a rise in serum metal ion levels after the metal implantation in maxillofacial region. None of the patients had any abnormal signs and symptoms due to raised metal levels. Further studies are warranted to correlate the serum metal ion levels and their clinical relevance.

Can Superoxide Anions Predict the Malignant Potential of Carotid body Tumor? - A Pilot Study.

Currently, there is no consensus on estimating the malignant potential of Carotid Body Tumor (CBT) and the only way to predict a metastatic CBT is through DOTANOC Positron Emission Tomography (PET) scan. There is a well-established correlation between CBT and superoxide anions inside tumor cells. The purpose of this pilot study was to measure superoxide anions inside CBT cells and find if these can be used as marker to predict malignant potential of CBT. The results were also co-related with findings of DOTANOC PET scan retrospectively. The CBT tissue from 10 patients was stained using a fluorogenic dye and superoxide anions were measured by analysis of fluorescent image. The patients were divided into two groups - First group with four patients having potentially malignant CBT based upon clinico-surgical characteristics and second group with the rest of the six patients. It was seen that the superoxide anions were highest in the first group which included patients with metastatic carotid body tumor, patients with multiple paragangliomas and patient with positive family history (p = 0.011). The same patients also had metastasis and multiple tumors detected on DOTANOC PET scan. It was concluded that measuring superoxide anions in excised tumor tissue can be used to estimate malignant potential of CBT and can identify patients who truly require DOTANOC PET scan; without affecting the treatment, as it is an expensive investigation involving ionizing radiation and may not be available in all centres. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03623-6.

Effects of Self-management Program as Adjunctive to Usual Rehabilitation Exercise on Pain and Functional Outcomes in Knee Osteoarthritis: A Randomized Controlled Trial.

BACKGROUND: Home-based exercise (HBE) and patient education (EDU) have been reported as beneficial additions to usual knee osteoarthritis (KOA) rehabilitation. However, previous trials mostly examined the effects of HBE and EDU separately. Thus, this study aimed to evaluate the effects of a structured combined HBE and EDU program in addition to usual KOA rehabilitation on pain score, functional mobility, and disability level. STUDY DESIGN: A parallel-group, single-blinded randomized controlled trial. METHODS: Eighty adults with KOA were randomly allocated to experimental (n=40) and control (n=40) groups. All participants underwent their usual physiotherapy care weekly for eight weeks. The experimental group received a structured HBE+EDU program to their usual care, while the control group performed home stretching exercises to equate treatment time. The Knee Injury and Osteoarthritis Outcome Score (KOOS) for the disability level, visual analogue scale (VAS) for pain, and timed up-and-go test (TUG) for mobility were measured pre-post intervention. RESULTS: After eight weeks, the experimental group demonstrated significant improvements in the KOOS (all subscales), pain VAS, and TUG scores compared to baseline (P<0.001); meanwhile, only KOOS (activities of daily living and sports subscales) was significant in the control group. Relative to the control, the experimental group presented higher improvements (P<0.001) by 22.2%, 44.1%, and 15.7% for KOOS, pain VAS, and TUG, respectively. CONCLUSION: Integrating the HBE+EDU program into usual KOA rehabilitation could reduce pain and disability, while it improved functional mobility. The finding of this study suggests a combination of a structured HBE and EDU program to be considered as part of mainstream KOA management.

Apoptotic and Degenerative Changes in the Enteric Nervous System Following Exposure to Fluoride During Pre- and Post-natal Periods.

Children born in fluorosis endemic areas usually suffer from gastrointestinal complications and are unable to attain normal growth as per their age group. The enteric nervous system (ENS) controls gut movement and functions. It is highly vulnerable to any ingested toxins. Based on observations, it was hypothesized that fluoride exposure during pregnancy and lactation might induce ENS developmental defects. The aim of this study is to investigate the effects of fluoride exposure during pregnancy and lactation on ENS of the first-generation rat pups. After confirmation of pregnancy, female rats were divided into 3 groups and kept on normal water (group 1), 50 ppm of fluoride (group 2), and 100 ppm of fluoride (group 3). The fluoride exposure started at the start of pregnancy and continued until lactation. On the 21st post-natal day, the pups were euthanized and the gut tissue and blood were harvested and subjected to fluoride measurement, oxidative stress estimation, histopathological and ultrastructural analysis, TUNEL, and immunofluorescence. The quantitative expressional analysis of embryonic lethal abnormal vision-like 4 (ELAVL4) (a pan-neuronal marker) and glial fibrillary acidic protein (GFAP) (a glial cell marker) genes was performed by RT-qPCR. An increase in oxidative stress, subcellular and cellular injuries, and apoptosis in enteric neuronal, glial, and epithelial cells was observed in the distal colon of the first-generation pups. Ganglionic degeneration, reduced expression of HuC/D and GFAP, altered colon muscle layer thickness, and tissue edema were observed in the fluoride-treated groups compared with the control. Fluoride exposure during prenatal and lactation period leads to subcellular and cellular injuries due to increased oxidative stress and apoptosis in the ENS. The reduction in the number of neurons and glia due to increased apoptosis may cause alterations in ENS development.

Physical property and gas transport studies of ultrathin polysulfone membrane from 298.15 to 328.15 K and 2 to 50 bar: atomistic molecular simulation and empirical modelling.

Elucidation of ultrathin polymeric membrane at the laboratory scale is complicated at different operating conditions due to limitation of instruments to obtain in situ measurement data of membrane physical properties. This is essential since their effects are reversible. In addition, tedious experimental work is required to collect gas transport data at varying operating conditions. Recently, we have proposed a validated Soft Confining Methodology for Ultrathin Films that can be used to simulate ultrathin polysulfone (PSF) membranes upon confinement limited to 308.15 K and 2 bars. In industry application, these ultrathin membranes are operated within 298.15-328.15 K and up to 50 bars. Therefore, our proposed methodology using computational chemistry has been adapted to circumvent limitation in experimental study by simulating ultrathin PSF membranes upon confinement at different operating temperatures (298.15 to 328.15 K) and pressures (2 to 50 bar). The effect of operating parameters towards non-bonded and potential energy, free volume, specific volume and gas transport data (e.g. solubility and diffusivity) for oxygen and nitrogen of the ultrathin films has been simulated and collected using molecular simulation. Our previous empirical equations that have been confined to thickness dependent gas transport properties have been modified to accommodate the effect of operating parameters. The empirical equations are able to provide a good quantitative characterization with R 2 ≥ 0.99 consistently, and are able to be interpolated to predict gas transport properties within the range of operating conditions. The modified empirical model can be utilized in process optimization studies to determine optimal membrane design for typical membrane specifications and operating parameters used in industrial applications.

Dictyostelium discoideum plasma membranes contain an actin-nucleating activity that requires ponticulin, an integral membrane glycoprotein.

In previous equilibrium binding studies, Dictyostelium discoideum plasma membranes have been shown to bind actin and to recruit actin into filaments at the membrane surface. However, little is known about the kinetic pathway(s) through which actin assembles at these, or other, membranes. We have used actin fluorescently labeled with N-(1-pyrenyl)iodoacetamide to examine the kinetics of actin assembly in the presence of D. discoideum plasma membranes. We find that these membranes increase the rate of actin polymerization. The rate of membrane-mediated actin polymerization is linearly dependent on membrane protein concentrations up to 20 micrograms/ml. Nucleation (the association of activated actin monomers into oligomers) appears to be the primary step of polymerization that is accelerated. A sole effect on the initial salt-induced actin conformational change (activation) is ruled out because membranes accelerate the polymerization of pre-activated actin as well as actin activated in the presence of membranes. Elongation of preexisting filaments also is not the major step of polymerization facilitated by membranes since membranes stripped of all peripheral components, including actin, increase the rate of actin assembly to about the same extent as do membranes containing small amounts of endogenous actin. Acceleration of the nucleation step by membranes also is supported by an analysis of the dependence of polymerization lag time on actin concentration. The barbed ends of membrane-induced actin nuclei are not obstructed by the membranes because the barbed end blocking agent, cytochalasin D, reduces the rate of membrane-mediated actin nucleation. Similarly, the pointed ends of the nuclei are not blocked by membranes since the depolymerization rate of gelsolin-capped actin is unchanged in the presence of membranes. These results are consistent with previous observations of lateral interactions between membranes and actin filaments. These results also are consistent with two predictions from a model based on equilibrium binding studies; i.e., that plasma membranes should nucleate actin assembly and that membrane-bound actin nuclei should have both ends free (Schwartz, M. A., and E. J. Luna. 1988. J. Cell Biol. 107:201-209). Integral membrane proteins mediate the actin nucleation activity because activity is eliminated by heat denaturation, treatment with reducing agents, or proteolysis of membranes. Activity also is abolished by solubilization with octylglucoside but is reconstituted upon removal or dilution of the detergent. Ponticulin, the major actin-binding protein in plasma membranes, appears to be necessary for nucleation activity since activity is not reconstituted from detergent extracts depleted of ponticulin.

The integral membrane protein, ponticulin, acts as a monomer in nucleating actin assembly.

Ponticulin, an F-actin binding transmembrane glycoprotein in Dictyostelium plasma membranes, was isolated by detergent extraction from cytoskeletons and purified to homogeneity. Ponticulin is an abundant membrane protein, averaging approximately 10(6) copies/cell, with an estimated surface density of approximately 300 per microns2. Ponticulin solubilized in octylglucoside exhibited hydrodynamic properties consistent with a ponticulin monomer in a spherical or slightly ellipsoidal detergent micelle with a total molecular mass of 56 +/- 6 kD. Purified ponticulin nucleated actin polymerization when reconstituted into Dictyostelium lipid vesicles, but not when a number of commercially available lipids and lipid mixtures were substituted for the endogenous lipid. The specific activity was consistent with that expected for a protein comprising 0.7 +/- 0.4%, by mass, of the plasma membrane protein. Ponticulin in octylglucoside micelles bound F-actin but did not nucleate actin assembly. Thus, ponticulin-mediated nucleation activity was sensitive to the lipid environment, a result frequently observed with transmembrane proteins. At most concentrations of Dictyostelium lipid, nucleation activity increased linearly with increasing amounts of ponticulin, suggesting that the nucleating species is a ponticulin monomer. Consistent with previous observations of lateral interactions between actin filaments and Dictyostelium plasma membranes, both ends of ponticulin-nucleated actin filaments appeared to be free for monomer assembly and disassembly. Our results indicate that ponticulin is a major membrane protein in Dictyostelium and that, in the proper lipid matrix, it is sufficient for lateral nucleation of actin assembly. To date, ponticulin is the only integral membrane protein known to directly nucleate actin polymerization.

Diacylglycerol-stimulated formation of actin nucleation sites at plasma membranes.

Diacylglycerols, which are generated during phospholipase-catalyzed hydrolysis of phospholipids, stimulated actin polymerization in the presence of highly purified plasma membranes from the cellular slime mold Dictyostelium discoideum. The increased rate of actin polymerization apparently resulted from de novo formation of actin nucleation sites rather than uncapping of existing filament ends, because the membranes lacked detectable endogenous actin. The increased actin nucleation was mediated by a peripheral membrane component other than protein kinase C, the classical target of diacylglycerol action. These results indicate that diacylglycerols increase actin nucleation at plasma membranes and suggest a mechanism whereby signal transduction pathways may control cytoskeletal assembly.

Role of Nursing Informatics in Implementation of SNOMED-CT in India.

SNOMED-CT project under the Ministry of Health and Family Welfare is operational at AIIMS since July 2016. A team of nurses were recruited under SNOMED project who actively works for integrating existing EHR with SNOMED-CT, monitoring, training of users auditing the data, resets creation and development of National Drug Database. This paper emphasizes role of Nursing Informatics in implementation of SNOMED-CT project in India as well as in any other country.