Measuring the needs of older adult patients in intensive care units: A translation and validation study of the NAPinICU questionnaire.

The NAPinICU questionnaire, specifically designed to assess the needs of older adult patients in intensive care units, serves as a valuable tool for understanding and addressing their unique requirements. This study applied a cross-cultural translation process, followed by a cross-sectional survey to measure patients' needs and evaluate the psychometric properties of the Arabic-translated version of the NAPinICU questionnaire. The older adults' translated questionnaire demonstrated high content validity, good test-retest reliability and acceptable internal consistency. Discriminative validity confirmed significant differences in needs ratings between university and private hospital patients. This translated and validated tool can help in assessing the needs of older adults in intensive care units. Assessment of these patients' needs assists in enhancing the quality of care delivered to them by nurses and other healthcare providers.

Predictors of critical care nurses' stress, anxiety, and depression in response to COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic directly affects the psychological well-being of critical care nurses. Several studies had investigated the psychological impact of the pandemic on nurses caring for patients with COVID-19, but few were conducted to identify the predictors of this impact. AIMS: The objective of this study is to identify the predictors of critical care nurses' stress, anxiety, and depression in response to the COVID-19 pandemic. DESIGN: A cross-sectional survey was conducted in five intensive care units in five hospitals in Alexandria, Egypt. METHODS: An online questionnaire was distributed. It included socio-demographic and work-related data and the depression, anxiety, and stress scale scores of the nurses under study. A multiple linear regression model was developed to identify the predictors of critical care nurses' stress, anxiety, and depression in response to the COVID-19 pandemic. RESULTS: Two hundred (64%) of 308 nurses completed the electronic questionnaire. Significant predictors of stress included the number of infected colleagues (P < .001) and availability of hospital resources (P = .01). Significant predictors of anxiety were age, gender, satisfactory income (P < .001), years of experience, time spent caring for patients with COVID-19 (P = .04), continuous training, number of infected colleagues (P = .01), and availability of hospital resources (P = .02). Finally, significant predictors of depression included gender, history of physical problems (P = .04), educational attainment, availability of hospital resources, history of psychological problems (P < .001), and number of infected colleagues (P = .001). CONCLUSION: The hospital's lack of human and physical resources and the number of colleagues infected with COVID-19 were the strongest predictors of stress, anxiety, and depression among nurses. RELEVANCE TO CLINICAL PRACTICE: Identifying the predictors of stress, anxiety, and depression among nurses who care for patients with COVID-19 is a vital step in developing mental health promotion strategies to support nurses during this pandemic.

The effect of reverse Trendelenburg position versus semi-recumbent position on respiratory parameters of obese critically ill patients: A randomised controlled trial.

AIMS AND OBJECTIVES: To investigate the effect of reverse Trendelenburg position versus semi-recumbent position on respiratory parameters of obese critically ill patients. BACKGROUND: Reverse Trendelenburg position is recommended for obese patients; however, the effect among critically ill patients, especially those on mechanical ventilation, has limited study. DESIGN: Randomised, controlled pretest, repeated post-test trial with two parallel groups. METHODS: The study started from 13 January 2020-12 March 2020. Adult critically ill patients with a body mass index ≥30 were randomly assigned by computer-generated randomisation to either reverse Trendelenburg position group (intervention) or semi-recumbent position group (active comparator control). Outcome measures were ventilation parameters (dynamic compliance, partial pressure of arterial carbon dioxide and minute volume) and oxygenation parameters (hypoxaemic index and partial pressure of arterial oxygen). Measures were assessed immediately before positioning and after positioning in 10 minutes, 20 minutes and 30 minutes. CONSORT checklist was used to report the current study. SETTINGS: Four general intensive care units. RESULTS: One hundred and ten patients (55 patients in each group) completed the study. The reverse Trendelenburg position group had a higher improvement than the semi-recumbent position group as estimated by mean differences in their dynamic compliance, minute volume, partial pressure of carbon dioxide, partial pressure of oxygen and hypoxaemic index. CONCLUSION: Reverse Trendelenburg position improves obese patients' respiratory parameters more than semi-recumbent position. RELEVANCE TO CLINICAL PRACTICE: This study directs nurses to use the reverse Trendelenburg position, which is an important position for enhancing the parameters of ventilation and oxygenation of obese mechanically ventilated patients.

Cortical tau burden and behavioural dysfunctions in mice exposed to monosodium glutamate in early life.

Although monosodium glutamate (MSG)-induced neurotoxicity has been recognized for decades, the potential similarities of the MSG model to Alzheimer's disease (AD)-type neuropathology have only recently been investigated. MSG-treated mice were examined behaviourally and histologically in relation to some features of AD. Four-week old mice received 5 subcutaneous MSG (2 g/kg) injections on alternate days, or saline. At age 10-12 weeks, they were given a battery of behavioural tests for species-typical behaviours and working memory. The mice were killed at 12 weeks and the brains excised. Accumulation of hyperphosphorylated tau protein was assessed in cortical and hippocampal neurons by immunohistochemistry, and in cerebral cortical homogenates. A 78% increase in cortical concentrations of phosphorylated tau protein was observed in the MSG mice. Intracellular hyperphosphorylated tau immunostaining was observed diffusely in the cortex and hippocampus, together with cortical atrophic neurons, extensive vacuolation and dysmorphic neuropil suggestive of spongiform neurodegeneration. Nest-building was significantly impaired, and spontaneous T-maze alternation was reduced, suggesting defective short-term working memory. Subcutaneous MSG treatment also induced a 56% reduction in exploratory head dips in a holeboard (P = 0.009), and a non-significant tendency for decreased burrowing behaviour (P = 0.085). These effects occurred in the absence of MSG-induced obesity or gross locomotor deficits. The findings point to subcutaneous MSG administration in early life as a cause of tau pathology and compromised species-typical behaviour in rodents. Determining whether MSG can be useful in modelling AD requires further studies of longer duration and full behavioural characterization.

Monosodium glutamate neurotoxicity increases beta amyloid in the rat hippocampus: a potential role for cyclic AMP protein kinase.

BACKGROUND: Glutamate excitotoxicity and cyclic AMP-activated protein kinase (AMPK) are both recognized as important mediators in neurodegenerative disorders including Alzheimer's disease (AD). OBJECTIVES: To investigate whether oral or subcutaneous monosodium glutamate (MSG) neurotoxicity mimics some features of AD and whether these can be reversed by the AMPK activator Pioglitazone. METHODS: Male Wistar rats aged 5 weeks were administered oral or subcutaneous MSG for 10 days with or without daily oral Pioglitazone. Two additional groups given only saline orally or subcutaneously acted as controls. At age 10 weeks the rats were subjected to neurobehavioral testing, then sacrificed for measurement of AMPK, ß-amyloid and Fas ligand in the hippocampus. RESULTS: Oral and subcutaneous MSG both induced a lowering of hippocampal AMPK by 43% and 31% respectively (P<0.05 for both) and >2-fold increase in hippocampal Fas ligand, a mediator of apoptosis (P<0.001 for both). MSG treatment also induced a significant increase in ß-amyloid in the hippocampus by >4-fold and >5-fold in the oral and subcutaneous groups. This was associated with increased latency before crossing to the white half in the black-white alley and before the first rear in the holeboard test, suggesting increased anxiety. Pioglitazone decreased hippocampal ß-amyloid accumulation and Fas ligand, but did not ameliorate the neurobehavioural deficits induced by MSG. CONCLUSIONS: MSG treatment enhances ß-amyloid accumulation in the rat hippocampus. Our results suggest a role for AMPK reduction in mediating the neurotoxic effects of glutamate, including ß-amyloid accumulation.

Role of activation of 5'-adenosine monophosphate-activated protein kinase in gastric ulcer healing in diabetic rats.

BACKGROUND: The potential utility of 5'-adenosine monophosphate-activated protein kinase (AMPK)-activating agents, such as metformin, in inducing angiogenesis, could be a promising approach to promote healing of gastric ulcers complicated by diabetes mellitus. The aim of the present study was to assess the effect of a drug that activates AMPK, namely metformin, in gastric ulcer healing in streptozotocin-induced diabetic rats. METHODS: Forty male Wistar albino rats were made diabetic by intraperitoneal (i.p.) streptozotocin injection and 10 rats were injected i.p. by a single dose of physiological saline. Six weeks following streptozotocin or saline injection, gastric ulcers were induced by serosal application of acetic acid. Three days after acetic acid application, rats were divided into group 1 (nondiabetic control), group 2 (streptozotocin-injected rats), groups 3-5 (streptozotocin-injected rats treated with metformin or metformin and an inhibitor of AMPK, namely compound C or pioglitazone) for 7 days following acetic acid application. RESULTS: Administration of metformin, but not pioglitazone, resulted in a significant decrease in the gastric ulcer area, a significant increase in epithelial regeneration assessed histologically, a significant increase in the number of microvessels in the ulcer margin, a significant increase in gastric vascular endothelial growth factor concentration and gastric von Willebrand factor as well as a significant increase in gastric phospho-AMPK. Compound C, an inhibitor of AMPK, blocked metformin-induced changes in assessed parameters suggesting that the effect of metformin was mediated mainly through activation of AMPK. CONCLUSION: Our results suggest the feasibility of a novel treatment strategy, namely drugs activating AMPK, for patients in whom impairment of ulcer healing constitutes a secondary complication of diabetes mellitus.

The possible role of estrogen and selective estrogen receptor modulators in a rat model of Parkinson's disease.

AIM: The aim of the present study was to assess and compare the effect of 17ß-estradiol and two different selective estrogen receptor modulators (SERMs), tamoxifen and raloxifene, as well as a selective estrogen receptor alpha agonist, propyl-pyrazole-triol (PPT) and a selective estrogen receptor beta agonist, diarylpropionitrile (DPN), on behavioral and biochemical alterations in 6-hydroxydopamine (6-OHDA)-induced nigral dopaminergic cell death in rats. MAIN METHODS: 80 female Wister rats were used. Animals were divided into eight equal groups: Group I; Sham operated, Group II; subjected to ovariectomy (OVX), Group III; OVX rats received striatal injection of 6-OHDA, Groups IV-VIII; OVX rats received striatal injection of 6-OHDA and were injected daily with 17ß-estradiol, tamoxifen, raloxifene, PPT and DPN respectively for 5days before 6-OHDA and continued for further 2weeks. KEY FINDINGS: Results showed that striatal injection of 6-OHDA produced significant behavioral alteration suggestive of PD, together with significant decrease in striatal dopamine, homovanillic acid (HVA) and 3,4-dihydroxyphenyl acetic acid (DOPAC) concentrations. 6-OHDA-induced nigral dopaminergic cell death was characterized by oxidative stress, evidenced by significant decrease in striatal glutathione peroxidase activity, as well as apoptosis, evidenced by significant increase in nigral caspase-3 activity. Treatment with 17ß-estradiol, raloxifene, PPT, but neither tamoxifen nor DPN, resulted in significant amelioration of the behavioral and biochemical alterations induced by 6-OHDA. SIGNIFICANCE: These findings suggest that estrogen and some SERMs having estrogenic agonist activity in the brain, like raloxifene, might exert beneficial effect in PD.

Study of the effect of inhibiting galanin in Alzheimer's disease induced in rats.

It is recently reported that galanin plays a role in memory decline that is the primary behavioral symptom of Alzheimer's disease. The aim of the present study was to study the impact of administration of two antidiabetic drugs that might inhibit galanin, namely glibenclamide and pioglitazone, on the behavioral, and neurochemical changes in Alzheimer's disease--induced in rats by intracerebroventricular (i.c.v.) injection of beta amyloid (Abeta). The present study was conducted on 60 male Wistar rats that were divided into 6 groups: group I (control group) which received i.c.v. scrambled peptide, group II (i.c.v.-Abeta group) which received i.c.v.-Abeta, groups III and IV that received, respectively, glibenclamide and pioglitazone daily orally for 3 weeks following scrambled peptide administration as well as groups V and VI that received, respectively, glibenclamide and pioglitazone daily orally for 3 weeks following Abeta administration. i.c.v.-Abeta resulted in significant behavioral alterations suggesting Alzheimer's disease, where there was significant impairment in spatial cognition, evaluated by Morris water maze task, and in learning and memory performance, assessed using passive-avoidance learning task. i.c.v.-Abeta also resulted in significant increase in hippocampal hyperphosphorylated tau protein as well as galanin. Administration of studied antidiabetic drugs, glibenclamide and pioglitazone, resulted in significant improvement in spatial cognition and in learning and memory performance, as well as significant decrease in hippocampal hyperphosphorylated tau protein and hippocampal galanin. Our findings suggest that a pharmacologic approach to inhibit galanin in the brain, either by glibenclamide or pioglitazone might dramatically improve symptoms in Alzheimer's disease.

Targeting apoptosis in the heart of streptozotocin-induced diabetic rats.

OBJECTIVES: The aim of the current study was to address the issue of cardiomyocyte apoptosis as a possible contributor in the development of diabetic cardiomyopathy and whether it would be possible to suppress this apoptosis by the use of a peroxisome proliferator-activated receptor (PPAR)-alpha agonist (fenofibrate) or a PPAR-gamma agonist (rosiglitazone). METHODS: Ten normal male albino rats (group I) were injected intraperitoneally (IP) by a single dose of saline and served as a control for group II. Thirty male albino rats were made diabetic by IP streptozotocin (STZ) injection and were divided into 3 groups: group II (nontreated diabetic rats), groups III and IV (diabetic rats treated with PPAR-gamma agonist (rosiglitazone), and PPAR-alpha agonist (fenofibrate) respectively, for 12 weeks starting 1 week following STZ injection. RESULTS: The studied drugs decreased left ventricular to body weight ratio and cardiac: caspase-3, tumor necrosis factor-alpha, hydroxyproline, free fatty acids (FFAs) as well as triglycerides (TGs) and improved oxidative stress parameters as well as left ventricular papillary muscle developed tension (DT). CONCLUSIONS: The results of the current study support the hypothesis that apoptosis plays a key role in the pathophysiology of diabetic cardiomyopathy and demonstrate that the use of PPAR-alpha and -gamma agonists might have a protective role against diabetic cardiomyopathy.

Role of modulation of vascular endothelial growth factor and tumor necrosis factor-alpha in gastric ulcer healing in diabetic rats.

The aim of the present study was to assess the effect of drugs that increase gastric vascular endothelial growth factor (VEGF) and suppress gastric tumor necrosis factor-alpha (TNF-alpha) in gastric ulcer healing in streptozotocin-induced diabetic rats. Sixty male albino rats were made diabetic by intraperitoneal (i.p.) streptozotocin injection and ten rats were injected i.p. by a single dose of saline. Six weeks following streptozotocin or saline injection, gastric ulcers were induced by serosal application of acetic acid. Three days after acetic acid application, rats were divided into: group I (non-diabetic control), group II (streptozotocin-injected), groups III-VII (streptozotocin-injected rats treated with insulin, insulin and pentoxifylline, insulin and simvastatin, pentoxifylline as well as simvastatin, respectively, for 7 days following acetic acid application. The use of insulin, combinations of insulin and pentoxifylline or simvastatin resulted in a significant decrease in gastric ulcer area, significant increase in epithelial regeneration assessed histologically, significant increase in gastric VEGF concentration, and gastric von Willebrand factor (vWF) as well as significant decrease in gastric TNF-alpha. A significant difference in gastric ulcer area as well as in gastric TNF-alpha, VEGF and vWF levels could be observed between rats that received combinations of insulin and pentoxifylline or simvastatin compared to rats that received either drug alone. Our results suggest the feasibility of a novel treatment strategy, namely pentoxifylline and simvastatin, for patients in whom impairment of ulcer healing constitutes a secondary complication of diabetes mellitus.

Effect of targeting mitogen-activated protein kinase on cardiac remodeling in rats.

BACKGROUND: Increasing evidence suggests that the activation of p38 mitogen-activated protein kinase (p38MAPK) plays a role in cardiac remodeling. Targeting p38MAPK using drugs reported to interfere with its phosphorylation, namely statins and all-trans retinoic acid (atRA), might play a role in ameliorating this remodeling. METHODS AND RESULTS: Cardiac remodeling was induced in male albino rats by chronic inhibition of nitric oxide (NO) synthesis by N-nitro L-arginine methyl ester (L-NAME). Daily oral administration of L-NAME for 4 weeks resulted in the elevation of mean arterial blood pressure (MABP) together with cardiac remodeling evidenced by an increase in left ventricular-body weight ratio together with an increase in cardiac hydroxyproline concentration and a decrease in left ventricular papillary muscle-developed tension. An elevation in cardiac phosphorylated p38MAPK concentration, tumor necrosis factor alpha concentration and in cardiac caspase 3 activity was also observed. Administration of either rosuvastatin or all-trans retinoic acid (atRA), starting 4 weeks after L-NAME administration, ameliorated remodeling and improved all studied parameters. CONCLUSIONS: Targeting MAPK might represent a useful therapeutic avenue to ameliorate cardiac remodeling and support the notion that atRA and statins are potential candidates for the prevention and therapy of cardiac remodeling.

Do desipramine [10,11-dihydro-5-[3-(methylamino) propyl]-5H-dibenz[b,f]azepine monohydrochloride] and fluoxetine [N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]-propan-1-amine] ameliorate the extent of colonic damage induced by acetic acid in rats?

The present study was designed to compare the anti-inflammatory and antioxidant effects of two antidepressant drugs, desipramine [10,11-dihydro-5-[3-(methylamino) propyl]-5H-dibenz-[b,f]azepine monohydrochloride] and fluoxetine [N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]-propan-1-amine], administered with variable doses, on experimentally induced colitis in rats. Two doses for each drug (10 and 20 mg/kg/day i.p.) were injected in 48 adult male albino rats for 2 weeks after induction of colitis by intracolonic administration of 2 ml of 3% acetic acid. Several parameters, including macroscopic (ulcer score index) and biochemical such as myeloperoxidase (MPO), reduced glutathione (GSH), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta, were measured using standard assay procedures. The study demonstrates that both desipramine and fluoxetine significantly attenuated the extent and the severity of the macroscopic signs of cell damage. Both drugs significantly reduced tissue MPO activity in a dose-dependent manner. Both desipramine and fluoxetine, at either dose, significantly increased GSH in colonic tissue. Desipramine and fluoxetine, at either dose, significantly reduced TNF-alpha and IL-beta. Desipramine at the dose of 20 mg/kg produced more decrease in the level of TNF-alpha compared with the effect of the smaller dose, but fluoxetine at 10 mg/kg diminished more in the level of IL-1beta compared with the effect of the larger dose. The present data indicate that both desipramine and fluoxetine have anti-inflammatory and antioxidants effects in experimentally induced colitis in rats, opening the avenue to their possible protective role in patients with inflammatory bowel disease.

Synthesis and biological evaluation of some thiazolyl and thiadiazolyl derivatives of 1H-pyrazole as anti-inflammatory antimicrobial agents.

Four series of pyrazolyl benzenesulfonamide derivatives have been synthesized. The first series was prepared by cyclization of the intermediate N,N-dimethylaminomethylene-4[3-phenyl-4-(substituted thiosemicarbamoyl hydrazonomethyl)-1H-pyrazol-1-yl]benzenesulfonamide 2a-c with ethyl bromoacetate to afford the corresponding thiazolidinyl derivatives 3a-c. The second series was prepared by cyclization of the key intermediates 2a-c with 4-bromophenacyl bromide giving rise to thiazolinyl derivatives 4a-c. Thiadiazolyl derivatives 5a-c were obtained by heating 2a-c with 2M FeCl(3) solution. Refluxing the intermediates 2a-c in acetic anhydride yielded the corresponding thiadiazolinyl derivatives 6a-c. All the target compounds showed anti-inflammatory activity and three of them 3b, 3c and 4c surpassed that of indomethacin both locally and systemically in the cotton pellet granuloma and rat paw edema bioassay. The active compounds showed selective inhibitory activity towards COX-2 enzyme as revealed by the in vitro enzymatic assay. All the tested compounds proved to have superior gastrointestinal (GI) safety profiles as compared to indomethacin, when tested for their ulcerogenic effects. The acute toxicity study of compounds having promising anti-inflammatory activity (3b, 3c and 4c) indicated that they are well tolerated both orally and parenterally. Antimicrobial activity tests expressed as minimal inhibitory concentrations (MIC), revealed that compounds 3b and 4a showed comparable antibacterial activity to that of ampicillin against Escherichia coli, while compounds 3a, 3c and 4a possessed about half the activity of ampicillin against Staphylococcus aureus. On the other hand, the results showed that all the tested compounds have weak or no antifungal activity against Candida albicans except for compounds 6b and 6c that showed half the activity of the control antifungal drug used (clotrimazole).

Novel milrinone analogs of pyridine-3-carbonitrile derivatives as promising cardiotonic agents.

In an attempt to design new inotropic drugs for congestive heart failure (CHF) with less proarrhythmic potential, three series of compounds analogous to milrinone were prepared, namely, 4-aryl-6-(4-pyridyl)-2-oxo-1,2-dihydropyridine-3-carbonitriles 2a-g, 4-aryl-6-(4-pyridyl)-2-thioxo-1,2-dihydropyridine-3-carbonitriles 3a-g and 2-amino-4-aryl-6-(4-pyridyl)-pyridine-3-carbonitriles 4a-g. The first series was prepared by reacting 4-acetyl pyridine with the appropriate aldehyde, ethyl cyanoacetate and ammonium acetate in ethanol. Reaction of 2a-g with phosphorus pentasulfide afforded the second series 3a-g. The third target compounds 4a-g were prepared applying the same procedure used to synthesize 2a-g using malononitrile instead of ethyl cyanoacetate. All the newly synthesized compounds were evaluated for their cardiotonic activity and their in vivo cardiovascular effects. In addition, their oral and parenteral acute toxicity were determined. Compounds 2a, 2b, 2c, 4c and 4f proved to exert cardiotonic activity comparable to that of milrinone using spontaneously beating atria model from reserpine-treated guinea pigs. In addition these compounds proved to be non-toxic and well tolerated by mice up to 250 mg kg(-1) orally and up to 125 mg kg(-1) through parenteral route.

Design and synthesis of some substituted 1H-pyrazolyl-thiazolo[4,5-d]pyrimidines as anti-inflammatory-antimicrobial Agents.

The synthesis of two novel series of structurally related 1H-pyrazolyl derivatives of thiazolo[4,5-d]pyrimidines is described. All the newly synthesised compounds were examined for their in vivo anti-inflammatory activity in two different bioassays namely; cotton pellet-induced granuloma and carrageenan-induced paw edema in rats. The in vitro inhibitory activity of the most active compounds towards human COX-1 and COX-2 enzymes was also estimated. In addition, the ulcerogenic effects and acute toxicity (LD(50)) values of these compounds were determined. The same compounds were evaluated for their in vitro antimicrobial activity against Escherichia coli, as an example of Gram negative bacteria, Staphylococcus aureus as an example of Gram positive bacteria, and Candida albicans as a representative of fungi. The results revealed that compounds 5a, 9a, 9b, 10b and 12a exhibited anti-inflammatory activity comparable to that of indomethacin in both local and systemic in vivo animal models with no or minimal ulcerogenic effects (0-10%) and high safety margin (LD(50) > 500 mg kg(-1)). In addition, most of them displayed appreciable antibacterial activities when compared with ampicillin, especially against S. aureus. Compounds 9a and 12a are the most distinctive derivatives identified in the present study because of their remarkable in vivo and in vitro anti-inflammatory activity in addition to their pronounced antibacterial activities comparable to ampicillin against Gram positive and -negative bacteria. Therefore, they are considered as successful dual anti-inflammatory-antimicrobial candidates.