Fragment-based QSAR study to explore the structural requirements of DPP-4 inhibitors: a stepping stone towards better type 2 diabetes mellitus management.

Dipeptidyl peptidase-4 (DPP-4) inhibitors belong to a prominent group of pharmaceutical agents that are used in the governance of type 2 diabetes mellitus (T2DM). They exert their antidiabetic effects by inhibiting the incretin hormones like glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide which, play a pivotal role in the regulation of blood glucose homoeostasis in our body. DPP-4 inhibitors have emerged as an important class of oral antidiabetic drugs for the treatment of T2DM. Surprisingly, only a few 2D-QSAR studies have been reported on DPP-4 inhibitors. Here, fragment-based QSAR (Laplacian-modified Bayesian modelling and Recursive partitioning (RP) approaches have been utilized on a dataset of 108 DPP-4 inhibitors to achieve a deeper understanding of the association among their molecular structures. The Bayesian analysis demonstrated satisfactory ROC values for the training as well as the test sets. Meanwhile, the RP analysis resulted in decision tree 3 with 2 leaves (Tree 3: 2 leaves). This present study is an effort to get an insight into the pivotal fragments modulating DPP-4 inhibition.

Nosocomial Infection Among Burn Patients Admitted to a Tertiary Care Hospital of Bangladesh: A Cross-Sectional Study.

Nosocomial infection is a major challenge for the appropriate management of burns. The present study aimed to investigate incidence, risk factors, and causative organisms of nosocomial infection in burn patients of Khulna, Bangladesh. This cross-sectional study was conducted among patients admitted to the Burn and Plastic Surgery Department of Khulna Medical College Hospital (KMCH) from January to December 2020. Relevant data were collected from the patients' hospital records. Samples of wound swabs and blood were collected and cultured in the microbiology laboratory of KMCH. Logistic regression models were used to determine risk factors for infective complications in burn patients. All statistical analyses were carried out using SPSS version 26.0. A total of 100 burn patients were included. Mean age was 29.2 years with a male-female ratio of 1.3:1. Flame burns were most prevalent among the patients (41%), followed by scald (23%) and electric burns (15%). Almost 40% patients had full thickness burn. The incidence of nosocomial infection was 42% (wound infection 33% and septicemia 9%). Total body surface area of burn >40% (OR 7.56, 95% CI 2.89-19.81), full thickness burn (OR 34.40, 95% CI 3.25-97.14) and prolonged hospital stay (aOR 1.31, 95% CI 1.15-1.51) were significant risk factors for nosocomial infection. Staphylococcus aureus was the most commonly isolated organism (45%), followed by Streptococcus (24%), Pseudomonas aeruginosa (19%) and Escherichia coli (12%). As the epidemiology of nosocomial infection is not the same in different health facilities, a facility-based comprehensive burn management protocol considering the local epidemiology and causative organisms of burn wound infection is crucial for the prevention and management of nosocomial infections in burn patients.

Les infections nosocomiales sont une préoccupation majeure du traitement bien conduit des brûlés. Cette étude a eu pour but d'évaluer l'incidence, les facteurs de risque de survenue et les bactéries isolées d'infections nosocomiales survenues dans le CTB de Kulna (Bangladesh). Elle a étudié les dossiers l'ensemble des 100 patients admis dans le CTB du CHU de Kulna en 2020. Les analyses bactériologiques ont été réalisées dans le laboratoire du CHU. Une régression logistique a été utilisée pour déterminer les facteurs de risque d'infection. Toutes les analyses statistiques ont été réalisées avec SSPS 26.0. L'âge moyen était de 29,2 ans, le sex-ratio de 1,3H/1F. Les flammes représentaient 41% des causes, les liquides 23% et l'électricité 15%. Quasiment 40% des patients avaient des brûlures profondes. L'incidence des accidents infectieux était de 42% (cutanée 33%, bactériémies 9%). Les facteurs de risque indépendants de survenue d'une infection étaient une atteinte sur >40 % SCT (OR 7,56; IC95 2,89-19,81), une brûlure profonde (OR 34,40 ; IC95 3,25-97,14) et un séjour prolongé (OR 1,31; IC95 1,15-1,51). Les quatre bactéries les plus fréquentes étaient S. aureus (45%), Streptococcus spp (24%), P. æruginosa (19%), et E. coli (12%). Les épidémiologies bactériennes variant selon les services d'où elles sont issues, c'est sur l'épidémiologie locale que doivent se centre les mesures de contrôle des infections nosocomiales.

Risk factors of non-alcoholic fatty liver disease.

This case control study was carried out in Mymensingh Medical College Hospital, Mymensingh, Bangladesh and Dhaka Medical College Hospital, Dhaka, Bangladesh from November 2010 to October 2011 to find out the risk factors of non-alcoholic fatty liver disease. A total of 90 participants (45 cases and 45 controls) were included. A higher proportion of patients with age >45 years were found in case group compared to control (51.1% vs. 15.6%). The mean age was significantly higher in case group 49.8±12.6 years. Males demonstrated their predominance in both case (62.2%) and control (68.9%) groups, although the two groups did not differ in terms of sex distribution. Body mass index demonstrates that 26.7% of patients in case group were of normal weight, 46.7% overweight and 26.7% obese. In the control group, two-thirds (68.9%) of the patients were of normal weight and 24.4% overweight and 7.8% obese. Diabetes and hypertension were significantly present in the case group than those in control counterparts 75.6% vs. 15.6% and 86.7% vs. 15.6 % respectively. The mean fasting blood glucose, ALT, total cholesterol and triglycerides were significantly higher in case group compared to control group 7.8±1.3 vs. 5.4±2.5mmol/L (p<0.001); 39.1±12.4 vs. 30.3±14.1IU/L, (p=0.002); 239.9±14.3 vs. 183.3±11.4mg/dl, (p<0.001) and 183.6±12.5 vs. 133.5±16.0mg/dl, (p<0.001) respectively. However, no significant difference was observed between the case and the control groups in terms of HDL cholesterol (35.9±1.2 vs. 38.0±1.1mg/dl, p=0.203). Majority of the patients in case group (88.9%) exhibited increased echogenicity of liver on ultrasonogram as opposed to 15.6% in the control group.

A comparative assessment of waste incinerators in the UK.

The uptake in Europe of Energy from Waste (EfW) incinerator plants has increased rapidly in recent years. In the UK, 25 municipal waste incinerators with energy recovery are now in operation; however, their waste supply chains and business practices vary significantly. With over a hundred more plant developments being considered it is important to establish best business practices for ensuring efficient environmental and operational performance. By reviewing the 25 plants we identify four suitable case study plants to compare technologies (moving grate, fluidised bed and rotary kiln), plant economics and operations. Using data collected from annual reports and through interviews and site visits we provide recommendations for improving the supply chain for waste incinerators and highlight the current issues and challenges faced by the industry. We find that plants using moving grate have a high availability of 87-92%. However, compared to the fluidised bed and rotary kiln, quantities of bottom ash and emissions of hydrogen chloride and carbon monoxide are high. The uptake of integrated recycling practices, combined heat and power, and post incineration non-ferrous metal collections needs to be increased among EfW incinerators in the UK. We conclude that one of the major difficulties encountered by waste facilities is the appropriate selection of technology, capacity, site, waste suppliers and heat consumers. This study will be of particular value to EfW plant developers, government authorities and researchers working within the sector of waste management.

Performance measurement of intensive care services in hospitals: the case of Barbados

The Intensive Care Unit (ICU), being one of those vital areas of a hospital providing clinical care, the quality of service rendered must be monitored and measured quantitatively. It is, therefore, essential to know the performance of an ICU, in order to identify any deficits and enable the service providers to improve the quality of service. Although there have been many attempts to do this with the help of illness severity scoring systems, the relative lack of success using these methods has led to the search for a form of measurement which would encompass all the different aspects of an ICU in a holistic manner. The Analytic Hierarchy Process (AHP), a multiple-attribute, decision-making technique is utilised in this study to evolve a system to measure the performance of ICU services reliably. This tool has been applied to a surgical ICU in Barbados; we recommend AHP as a valuable tool to quantify the performance of an ICU.

Aqueous two-phase: the system of choice for extractive fermentation.

Extractive fermentation in aqueous two-phase systems is a meaningful approach to overcome low product yield in a conventional fermentation process, and by proper design of the two-phase system it is possible to obtain the product in a cell-free stream. The characteristics of an aqueous two-phase system, various polymers used for forming an aqueous two-phase system, the physicochemical parameters of the aqueous two-phase system, partitioning of biomolecules and cell mass and the effect of individual phase forming polymers on cell growth and product formation are reviewed in this article. The various extractive fermentation processes are also summarised here. At the end, the economic viability and scope of aqueous two-phase fermentation are briefly discussed in relation to the wider application of this topic.

Blood lead levels in children with neurological disorders.

Blood lead levels were measured by atomic absorption spectrometry in 82 children suffering from various neurological disorders (cerebral palsy 42, seizure disorders 35, acute encephalopathy of unknown origin 5) and in 28 healthy children, aged 1 to 12 years. Mean blood lead levels were 11.96 +/- 10.97 micrograms/dl in control children and 19.30 +/- 17.65 micrograms/dl in children with neurological disorders. A significant number of control children as well as those who had neurological disorders were found to have blood lead concentrations of > or = 10 micrograms/dl and > or = 20 micrograms/dl, the cut-off limits for lead poisoning and medical evaluation, respectively. Blood lead levels were, statistically, elevated in children with cerebral palsy compared to controls. Children with pica behaviour exhibited higher blood lead concentrations.

Alterations in the sensitivity of 5(th) receptor subtypes following chronic asvagandha treatment in rats.

Asvagandha (Withania somnifera) is an important antistress drug has now been sown to have an antidepressant action in clinically depressive patients, However, the mechanism of its antidepressant action has not been studied. Normal rats fed with asvagandha root extract (100mg/kg orally) for 4 and 8 weeks showed enhanced open field behavior and emotional stability along with a moderate but significant enhancement in the functional sensitivity of 5 HT2 receptors in the brain and a reciprocal subsensitivity of the 5HT1A receptors chronic asvagandha treatment (propylactically) was effective in preventing the behavioral deficit in open field activity in an animal model of depression. This was accompanied by an adaptive supersensitivity of the postsynaptic 5HT2 receptors in the brain. The effect of chronic Asvagandha on 5HT receptor subtypes is similar to the action of chronic ECT treatment and several antidepressant drugs.

Meconium aspiration syndrome: current concepts.

PIP: Aspiration of meconium causes considerable perinatal morbidity and mortality. Meconium-stained amniotic fluid (MSAF) is present in 7-22% of all deliveries. Gastrointestinal secretions, bile, bile acids, mucus, pancreatic juice, cellular debris, amniotic fluid, swallowed vernix caseosa, lanuge, and blood comprise meconium. Passage of meconium occurs most often in deliveries after 42 weeks gestation (30%) because of high levels of the hormone motilin. This hormone is responsible for bowel peristalsis, defecation, and maturation of the innervation of the intestinal tract associated with vagal stimulation. It tends to be a marker of pre/intrapartum asphyxia. MSAF is also a sign of fetal hypoxia or acidosis. It appears that meconium aspiration is predominantly an intrauterine event. The definition of meconium aspiration syndrome (MAS) is respiratory distress in a meconium-stained newborn, compatible radiographic findings (e.g., coarse, irregular pattern of increased density throughout the lung), and symptoms that can not otherwise be explained. MAS occurs in 1-4% of infants with MSAF and up to 10% of those with thick meconium. Mortality ranges from 6% to 40%. Initially, meconium particles mechanically obstruct the small airways. Later, chemical pneumonitis and interstitial edema are responsible for small airway obstruction. As many as 66% of persistent pulmonary hypertension of the newborn cases are associated with MAS. Clinical signs and symptoms of MAS include frothy, yellow-green secretions from the mouth; very rapid breathing; intercostal retractions; cyanosis; overinflated chest due to air trapping; rales; and rattling in the throat. Transcervical amnio-infusion of warmed normal saline may be an obstetric intervention in cases of MSAF. Intrapartum oropharyngeal suctioning and postpartum intratracheal suctioning has reduced the incidence of MAS. Routine care of MAS infants includes monitoring and correcting of the thermal environment and blood glucose and calcium levels. Chest physiotherapy, saline lavage, management of hypoxemia, surfactant therapy, and systemic steroid treatment are MAS therapies.^ieng

Probable involvement of serotonin in the increased permeability of the blood-brain barrier by forced swimming. An experimental study using Evans blue and 131I-sodium tracers in the rat.

The possibility that endogenous serotonin (5-hydroxytryptamine, 5-HT) participates in alteration of the blood-brain barrier (BBB) following short-term forced swimming (FS) exercise was examined in a rat model. Subjection of conscious young (age 8-9 weeks, 80-90 g) animals to continuous FS (at a water temperature of 30 +/- 1 degrees C) for 30 min, increased the permeability of the BBB to Evans blue albumin (EBA) and 131I-sodium in six and nine brain regions, respectively. The EBA staining was noted in posterior cingulate cortex, parietal, occipital cortices, cerebellar vermis, medial lateral cerebellar cortices and dorsal surface of hippocampus. In addition to these brain regions, the BBB permeability to 131I-sodium was further extended to caudate nucleus, thalamus and hypothalamus. This effect of FS on the BBB permeability was absent in adult (age 24-30 weeks, 300-400 g) animals. Measurement of 5-HT showed a profound increase of plasma and brain in young rats by 180% and 250%, respectively, from the control group. Adult animals showed only a minor increase in brain and plasma 5-HT levels. In young animals, pretreatment with p-CPA (a 5-HT synthesis inhibitor) and indomethacin (a prostaglandin synthesis inhibitor) prevented the FS induced increase in BBB permeability and 5-HT levels. Destruction of serotonergic neurons with 5,7-dihydroxytryptamine (5,7-DHT) reduced the breakdown of the BBB and attenuated the brain 5-HT level without affecting the plasma 5-HT. Cyproheptadine, ketanserin (5-HT2 receptor antagonists) and vinblastine (a vesicular transport inhibitor) prevented the increased permeability of the BBB alone. The plasma and brain 5-HT continued to remain high. These observations suggest that (i) 5-HT plays an important role in the breakdown of BBB permeability in FS, (ii) this effect of 5-HT on BBB permeability is mediated by 5-HT2 receptors, and (iii) FS induced increase in BBB permeability is age dependent.

Impairment of blood-brain barrier function by serotonin induces desynchronization of spontaneous cerebral cortical activity: experimental observations in the anaesthetized rat.

The possibility that elevation of serotonin in the circulation, which is found in various pathological states, influences the spontaneous cerebral cortical activity was examined in a rat model. The electroencephalogram was recorded using bipolar epidural electrodes placed over the frontal and parietal cerebral cortex. Intravenous infusion of serotonin (10 micrograms/kg per min for 10 min) decreased the electroencephalogram amplitude in both frontal and parietal recordings within 4 min of infusion. This decrease in amplitude was reversible, Pretreatment with cyproheptadine (a potent serotonin2 receptor antagonist) prevented the serotonin-induced decrease of the electroencephalogram amplitude. The blood-brain barrier permeability to Evans Blue and [131I]sodium was increased in frontal and parietal cortex. This increase in blood-brain barrier permeability was absent in animals pretreated with cyproheptadine. These results provide direct evidence that an elevated level of serotonin in blood has the capacity to influence spontaneous cortical electrical activity. This effect of serotonin on electroencephalogram appears to be due to its ability to enter into the brain parenchyma by inducing a short-term breakdown of the blood-brain barrier, probably via serotonin2 receptors.

Electrophysiological studies in children with paralytic poliomyelitis.

H-reflex latency (H-RL) and H/M ratio were measured in normal children and children with paralytic poliomyelitis of 1-3 years of age. The H-RL was considerably increased in both the involved and uninvolved limbs of the patients, whereas the H/M ratio did not differ. The Mmax value in the involved limb was very low, and therefore, a corrected H/M ratio was calculated for that side only. The corrected H/M ratio was significantly less than the H/M ratio observed in the uninvolved and control limbs. The distal motor latency was also increased in the involved side.

Role of serotonin and prostaglandins in brain edema induced by heat stress. An experimental study in the young rat.

The possibility that serotonin and prostaglandins participate in edema formation following heat stress (HS) was examined in young rats. Exposure of conscious young animals (8-9 weeks old) to heat at 38 degrees C in a biological oxygen demand (BOD) incubator (relative humidity 50-55%; wind velocity 20-25 cm/s) for 4 h resulted in marked increase in the whole brain water content (about 3%) as compared to animals kept at room temperature (21 degrees C). A marked extravasation of Evans blue and 131I-sodium occurred in the brain of heat exposed animals as compared to normal animals. Morphological examination using electron microscopy of selected brain regions of heat stressed animals showed profound cell changes. Thus perivascular edema, swollen neuronal and glial cells, membrane damage, vesiculation of myelin, axonal swelling and synaptic damage was frequent in this group of untreated animals. Pretreatment with ketanserin (a selective serotonin2 receptor antagonist) or indomethacin (an inhibitor of prostaglandin synthesis) markedly reduced edema formation after 4 h HS in young animals. These heat stressed animals had considerably less extravasation of protein tracers as compared to the untreated group. Cell changes and edema at the ultrastructural level were mainly absent. Our results suggest that serotonin and prostaglandins are involved in heat stress induced breakdown of the BBB permeability, edema formation, and cell damage.

Prostaglandins modulate alterations of microvascular permeability, blood flow, edema and serotonin levels following spinal cord injury: an experimental study in the rat.

The possibility that prostaglandins influence edema formation, microvascular permeability increase and reduction of blood flow following spinal cord trauma was examined in a rat model. In addition, the influence of prostaglandins on serotonin metabolism of the traumatized spinal cord was evaluated. Trauma to spinal cord (2-mm-deep and 5-mm-long incision in the right dorsal horn of T10-11 segments) resulted in a profound increase of the water content 5 h after injury. At this time, the microvascular permeability to Evans Blue and [131I]sodium was increased by 457 and 394%, respectively. The blood flow was reduced by 30%. The serotonin (5-hydroxytryptamine) content of the spinal cord increased by 205%. The plasma serotonin level rose by 152% in the injured group of rats. Pretreatment with indomethacin (10 mg/kg, i.p.) 30 min before trauma significantly reduced the edema and microvascular permeability increase. The local spinal cord blood flow of traumatized animals was partially restored. The increases of serotonin levels of the spinal cord and plasma were significantly attenuated. These beneficial effects of indomethacin were not present in rats given a lower dose (5 mg/kg). Indomethacin in either dose did not influence these parameters of control rats without trauma to the cord. Since indomethacin is a potential inhibitor of prostaglandins synthesis our observations indicate: (i) that prostaglandins participate in many microvascular responses (permeability changes, edema, blood flow) occurring after a trauma to the spinal cord; (ii) that these effects of the drug seem to be dose dependent, and (iii) that the prostaglandins may influence the serotonin metabolism following trauma to the spinal cord.

Regional metabolism of 5-hydroxytryptamine in brain under acute and chronic heat stress.

The metabolic alteration of 5-HT in four different regions of rat brain and plasma was studied under acute and chronic heat stress. A generalised elevation of 5-HT in all the brain regions along with high plasma level was observed in animals subjected to 4 hour heat stress at 38 degrees C. Such elevation of brain 5-HT may be due to entry of plasma 5-HT into the brain owing to breakdown of blood-brain barrier (BBB). In heat adapted rats, where BBB remained unaffected, no increase in brain 5-HT was observed, rather a significantly low level was maintained both in plasma and brain tissue.

Exercise training: significance of regional alterations in serotonin metabolism of rat brain in relation to antidepressant effect of exercise.

Alterations of 5HT and its chief metabolite 5HIAA were studied in four regions of the rat brain following acute 1-h swim exercise and 4 week chronic swim exercise (30 min/day, 6 days per week). Acute exercise significantly increased the synthesis and metabolism of 5HT in brain stem. Hypothalamus also showed increased levels of 5HT. However, no changes were observed in the cerebral cortex and hippocampus. Chronic exercise activated not only the synthesis but also the metabolism of 5HT in the cerebral cortex; this neuronal adaptation was sustained even 1 week after the termination of training. In brain stem, increased 5HT turnover was observed immediately after training. In hypothalamus, decrease in 5HT and 5HIAA levels occurred immediately after training, followed by a rebound increase in their levels after 1 week posttraining rest. In hippocampus, a delayed effect was observed, because 5HT level was unaltered immediately after the training, but its turnover decreased after 1 week rest. These findings have been discussed in an attempt to explain the antidepressant effect of exercise based on the 5HT deficiency theory of endogenous depression.