Copolymerization of ß-Butyrolactones into Functionalized Polyhydroxyalkanoates Using Aluminum Catalysts: Influence of the Initiator in the Ring-Opening Polymerization Mechanism.

Within bioplastics, natural poly(3-hydroxybutyrate) (PHB) stands out as fully biocompatible and biodegradable, even in marine environments; however, its high isotacticity and crystallinity limits its mechanical properties and hence its applications. PHB can also be synthesized with different tacticities via a catalytic ring-opening polymerization (ROP) of rac-ß-butyrolactone (BBL), paving the way to PHB with better thermomechanical and processability properties. In this work, the catalyst family is extended based on aluminum phenoxy-imine methyl catalyst [AlMeL2], that reveals efficient in the ROP of BBL, to the halogeno analogous complex [AlClL2]. As well, the impact on the ROP mechanism of different initiators is further explored with a particular focus in dimethylaminopyridine (DMAP), a hardly studied initiator for the ROP of BBL. A thorough mechanistic study is performed that evidences the presence of two concomitant DMAP-mediated mechanisms, that lead to either a DMAP or a crotonate end-capping group. Besides, in order to increase the possibilities of PHB post-polymerization functionalization, the introduction of a side-chain functionality is explored, establishing the copolymerization of BBL with ß-allyloxymethylene propiolactone (BPLOAll), resulting in well-defined P(BBL-co-BPLOAll) copolymers.

The Prevalence of Lewis, Lutheran, and P1 Antigens and Phenotypes in Southwestern Saudi Arabia.

BACKGROUND: Inherited hemoglobinopathies are common in Jazan Province, Saudi Arabia, and some patients may frequently require a blood transfusion. Therefore, the provision of compatible units using extended phenotypes is necessary to preclude the risk of alloimmunization. This study aimed to investigate the frequencies of the Lewis (LE), Lutheran (LU), and P1 antigens, as well as determine the prevalence of LE and LU phenotypes. METHODS: This study collected 150 blood samples from Saudi Arabian anonymous volunteering blood donors at Prince Muhammed bin Nasser Hospital in Jazan Province, Saudi Arabia. Serotyping was performed using antigen profile-II based on gel card technology to determine LE, LU, and P1 antigens. RESULTS: The prevalence of antigens was as follows: Lea (n = 37, 24.6%), Leb (n = 87, 58%), Lua (n = 6, 4%), Lub (n = 150, 100%), and P1 (n = 120, 80%). Regarding the LE phenotypes, Le (a+b-) was 24.7%, Le (a-b+) was 58%, and Le (a-b-) was 17.3%. The frequencies of only observed LU phenotypes Lu (a-b+) and Lu (a+b+) were 96% and 4%, respectively. CONCLUSIONS: In summary, this study reports LE, LU, and P1 antigen prevalence. Moreover, LE and LU phenotype frequencies were investigated. This study may help establish a national database of blood group antigens in Jazan Province, Saudi Arabia. Additionally, it may provide better transfusion practice to avoid the alloimmunization risk.

The association between preventive health and outpatient spending and life expectancy by income quartile.

BACKGROUND: To describe the relationship between longevity and local access to preventive healthcare at the county level. METHODS: We used Medicare outpatient reimbursement data from the 2010 Dartmouth Health Atlas and longevity data from Chetty et al. (2016) to identify the cross-sectional associations between county longevity, access to outpatient care, and the quality of primary care. RESULTS: We find that the cost of outpatient care is inversely correlated with area life expectancy for individuals in the bottom income quartile. Much of this correlation is driven by men in the bottom income quartile. We also find that disaggregating a preventive care index produces significant relationships between components of the index and longevity where none were previously found. CONCLUSIONS: These results counter prior assertions that local health costs are not associated with life expectancy. Additionally, the results also suggest that the local cost of outpatient care and the quality of that care may influence the longevity of low-income populations, especially for low-income men.

Is gene panel sequencing more efficient than clinical-based gene sequencing to diagnose autoinflammatory diseases? A randomized study.

The aim of this study was to compare the effectiveness of the gene-panel next-generation sequencing (NGS) strategy versus the clinical-based gene Sanger sequencing for the genetic diagnosis of autoinflammatory diseases (AIDs). Secondary goals were to describe the gene and mutation distribution in AID patients and to evaluate the impact of the genetic report on the patient's medical care and treatment. Patients with AID symptoms were enrolled prospectively and randomized to two arms, NGS (n = 99) (32-55 genes) and Sanger sequencing (n = 197) (one to four genes). Genotypes were classified as 'consistent/confirmatory', 'uncertain significance' or 'non-contributory'. The proportion of patients with pathogenic genotypes concordant with the AID phenotype (consistent/confirmatory) was significantly higher with NGS than Sanger sequencing [10 of 99 (10·1%) versus eight of 197 (4·1%)]. MEFV, ADA2 and MVK were the most represented genes with a consistent/confirmed genotype, whereas MEFV, NLRP3, NOD2 and TNFRSF1A were found in the 'uncertain significance' genotypes. Six months after the genetic report was sent, 54 of 128 (42·2%) patients had received effective treatment for their symptoms; 13 of 128 (10·2%) had started treatment after the genetic study. For 59 of 128 (46%) patients, the results had an impact on their overall care, independent of sequencing group and diagnostic conclusion. Targeted NGS improved the diagnosis and global care of patients with AIDs.

Recent Advances in Metal-Mediated Stereoselective Ring-Opening Polymerization of Functional Cyclic Esters towards Well-Defined Poly(hydroxy acid)s: From Stereoselectivity to Sequence-Control.

Poly(hydroxy acid)s are a family of biocompatible and (bio)degradable polyesters with various outcomes in different domains of application. To date, poly(hydroxy acid)s are best prepared by ring-opening polymerization (ROP) of the corresponding cyclic esters. Using racemic chiral monomers featuring side-chain groups enables to access, providing a stereoselective catalyst/initiator system is implemented, stereoregular functional polymers, thereby improving their physico-chemical properties, and ultimately, widening their range of uses. Here, we highlight a few important advances in metal-mediated stereoselective ROP of cyclic esters towards the synthesis of (functional) stereoregular poly(hydroxy acid)s that have recently been disclosed, emphasizing on (functional) ß- and γ-lactones, diolide and O-carboxyanhydride (OCA) monomers and yttrium-based catalysis. Fine-tuning of the substituents flanked on the catalyst ligand enables reaching poly(hydroxy acid)s with syndiotactic and also isotactic microstructures. The stereocontrol mechanisms at work and their probable origin, relying on steric but also electronic factors imparted in particular by the ligand substituents, are discussed. Taking advantage of such stereoselective ROPs, original copoly(hydroxy acid)s with gradient or alternated patterns then become accessible from the use of mixtures of chemically different, oppositely configured enantiopure monomers.

Nitrogen-Induced Transformation of Vitamin†C into Multifunctional Up-converting Carbon Nanodots in the Visible-NIR Range.

Water-soluble, biocompatible, and photoluminescent carbon nanodots have been obtained from the rationalized carbonization of vitamin C, a well-known antioxidant molecule in the presence of an amine co-reactant. Herein, we describe the positive influence of N-doping to induce a unique pH-dependent lifetime decay response that would be potentially attractive in biological backgrounds with intrinsic fluorescence fluctuations. In addition, the selectivity and sensitivity of the N-containing carbon nanoprobes towards the detection of copper ions at ppm levels is critically enhanced in comparison with the un-doped counterpart, especially in the near-infrared (NIR) range. Finally, the up-converting properties have been also successfully applied to image tumor cells in the visible range and remarkably, in the NIR region in which minimal tissue or water absorption and maximum penetration depth are expected.

The Neurobiological Mechanisms of Gamma-Hydroxybutyrate Dependence and Withdrawal and Their Clinical Relevance: A Review.

OBJECTIVE: x03B3;-Hydroxybutyrate (GHB) has gained popularity as a drug of abuse. In the Netherlands the number of patients in treatment for GHB dependence has increased sharply. Clinical presentation of GHB withdrawal can be life threatening. We aim, through this overview, to explore the neurobiological pathways causing GHB dependency and withdrawal, and their implications for treatment choices. METHODS: In this work we review the literature discussing the findings from animal models to clinical studies focused on the neurobiological pathways of endogenous but mainly exogenous GHB. RESULTS: Chronic abuse of GHB exerts multifarious neurotransmitter and neuromodulator effects on x03B3;-aminobutyric acid (GABA), glutamate, dopamine, serotonin, norepinephrine and cholinergic systems. Moreover, important effects on neurosteroidogenesis and oxytocin release are wielded. GHB acts mainly via a bidirectional effect on GABAB receptors (GABABR; subunits GABAB1 and GABAB2), depending on the subunit of the GIRK (G-protein-dependent ion inwardly rectifying potassium) channel involved, and an indirect effect of the cortical and limbic inputs outside the nucleus accumbens. GHB also activates a specific GHB receptor and ß1-subunits of α4-GABAAR. Reversing this complex interaction of neurobiological mechanisms by the abrupt cessation of GHB use results in a withdrawal syndrome with a diversity of symptoms of different intensity, depending on the pattern of GHB abuse. CONCLUSION: The GHB withdrawal symptoms cannot be related to a single mechanism or neurological pathway, which implies that different medication combinations are needed for treatment. A single drug class, such as benzodiazepines, gabapentin or antipsychotics, is unlikely to be sufficient to avoid life-threatening complications. Detoxification by means of titration and tapering of pharmaceutical GHB can be considered as a promising treatment that could make polypharmacy redundant.

Baclofen as relapse prevention in the treatment of gamma-hydroxybutyrate dependence: a case series.

In the last decade, gamma-hydroxybutyrate (GHB) abuse and dependence have increased. It has been reported that GHB dependence has a high rate of relapse, serious complications of intoxication, and a potentially life-threatening withdrawal syndrome. Nevertheless, in clinical practice, there is no known medical treatment to support GHB relapse prevention. We describe a case series of patients who were supported through an off-label treatment with baclofen to avoid a relapse into GHB abuse, for a period of 12 weeks. Nine of 11 patients did not relapse while taking a dose ranging from 30 to 60 mg per day, one patient relapsed after 5 weeks, and one stopped after 7 weeks. Baclofen was well tolerated; patients reported mild side effects such as fatigue, nausea, dry mouth, excessive sweating, and depressive feelings. Although systematic evidence is still lacking, our practice-based experience suggests that treatment with baclofen to assist abstinence might be effective in patients with GHB dependence. Further systematic controlled studies are necessary to establish the exact efficacy and safety of baclofen as relapse prevention for GHB-dependent patients.

Baclofen as relapse prevention in the treatment of Gamma- Hydroxybutyrate (GHB) dependence: an open label study.

BACKGROUND: GHB dependence is a growing health problem in several western countries, especially the Netherlands. Attempts to stop using GHB are often followed by relapse shortly after successful detoxification. Craving for GHB use and co-morbid psychiatric symptom levels are thought to be the major factors contributing to the high relapse rates. Given its pharmacological profile, baclofen might prove an effective anti-craving agent for patients with GHB dependence. The aim of the current study is to assess the potential of baclofen as an anti-craving agent relapse prevention intervention in GHB dependent patients. METHODS/DESIGN: In an open label non-randomized trial treatment with baclofen to a maximum of 60 mg/day will be compared with treatment as usual (TAU) in recently detoxified GHB dependent patients (n = 80). The primary outcome measure will be the level of GHB use. Secondary outcome measures are craving levels, psychiatric symptom levels and quality of life. Questionnaires will be administered during 12 weeks of baclofen treatment and at follow-up (six months after the start of treatment). DISCUSSION: It is hypothesized that baclofen treatment compared to TAU will be associated with significantly reduced GHB use. In addition, we hypothesize that baclofen treatment will be associated with decreased craving and anxiety levels, and higher quality of life. If results are in line with our hypotheses, further studies on the efficacy of baclofen using placebo controlled designs and long term follow-up are warranted. TRIAL REGISTRATION: The Netherlands Trial Register with number NTR4528 . Registered 19 April 2014.

OBSTACLES TO FAMILY PLANNING USE AMONG RURAL WOMEN IN ATIAK HEALTH CENTER IV, AMURU DISTRICT, NORTHERN UGANDA.

BACKGROUND: Uganda's rapid population growth (3.2%) since 1948 has placed more demands on health sector and lowered living standard of Ugandans resulting into 49% of people living in acute poverty especially in post conflict Northern Uganda. The population rise was due to low use of contraceptive methods (21% in rural areas and 43% in urban areas) and coupled with high unmet need for family planning (41%). This indicated poor access to reproductive health services. Effective use of family planning could reduce the rapid population growth. OBJECTIVE: To determine obstacles to family planning use among rural women in Northern Uganda. DESIGN: A descriptive cross-sectional analytical study. SETTING: Atiak Health Centre IV, Amuru District, rural Northern Uganda. SUBJECTS: Four hundred and twenty four females of reproductive ages were selected from both Inpatient and Outpatient Departments of Atiak Health Centre IV. RESULTS: There was high level of awareness 418 (98.6%), positive attitude 333 (78.6%) and fair level of utilisation 230 (54.2%) of family planning. However, significant obstacles to family planning usage included; long distance to Health facility, unavailability of preferred contraceptive methods, absenteeism of family planning providers, high cost of managing side effects, desire for big family size, children dying less than five years old, husbands forbidding women from using family planning and lack of community leaders' involvement in family planning programme. CONCLUSIONS: In spites of the high level of awareness, positive attitude, and free family planning services, there were obstacles that hindered family planning usage among these rural women. However, taking services close to people, reducing number of children dying before their fifth birthday, educating men about family planning, making sure family planning providers and methods are available, reducing cost of managing side effects and involving community leaders will improve utilisation of family planning and thus reduce the rapid population growth and poverty.

Rational design of a new fluorescent 'ON/OFF' xanthene dye for phosphate detection in live cells.

A new fluorescein derivative with ON/OFF features, 9-[1-(4-tert-butyl-2-methoxyphenyl)]-6-hydroxy-3H-xanthen-3-one (Granada Green, GG), was designed and synthesised. The new dye has spectral characteristics similar to those of other xanthenic derivatives but shows a higher pK(a) value for the equilibrium between its neutral and anionic forms. In addition, GG undergoes the same phosphate-mediated excited state proton transfer (ESPT) reaction as other xanthenic derivatives, giving rise to fluorescence decay traces that are dependent on both the phosphate concentration and pH of the medium. The phosphate-mediated ESPT reaction was employed to detect changes in the phosphate concentrations in live, permeabilised MC3T3-E1 preosteoblasts at pH 7.35. Its high pK(a) value indicates that this new dye is more sensitive as an intracellular phosphate sensor than other previously tested dyes, as experimentally demonstrated by its ability to detect a wider range of phosphate concentrations in biomimetic media and by the increased ratio of the phosphate concentration/decay time.

Behavioral assessment of intrinsically formed smart concrete using steel fibre and carbon black composite.

In recent years, health monitoring consists of the periodic observation and analysis of existing systems to predict and avoid structural breakdown, thereby saving lives and significantly lowering the cost of structural maintenance and repair. Normally, non-destructive testing techniques and sensor technology are used to detect damage in concrete structures are expensive in nature. Self-diagnosing or smart concrete has emerged a new paradigm in concrete research for damage detection. Smart concrete was cast by blending functional fillers such as carbon black, and steel fibers with concrete to improve the performance. Under various load conditions, the mechanical properties of the proposed smart concrete were examined. The electrical resistance of smart concrete was measured using the Four Probe Method and the Arduino UNO software. SEM and XRD were used to investigate the microstructures of intrinsically smart concrete. Thermogravimetric analysis was employed as a Non-Destructive Testing method to observe the hydration process. Furthermore, the obtained data were linked with the electrical resistivity of the smart concrete to assess corrosion damage. The electrical resistivity method is also an economical method and effective method to monitor the rate of corrosion.

Beyond Acculturation: Health and Immigrants' Social Integration in the United States.

Immigrants typically have more favorable health outcomes than their U.S.-born counterparts of the same race-ethnicity. However, little is known about how race-ethnicity and region of birth moderate the health outcomes of different immigrant groups as their tenure of U.S. residence increases. We study the association between time spent in the United States and health outcomes among non-Hispanic Black, non-Hispanic White, Asian, and Hispanic immigrants using National Health Interview Survey data. Although all immigrant groups initially report better health outcomes than their U.S.-born counterparts, the association between U.S. tenure and reported health outcomes varies among immigrants by race-ethnicity and region of birth. Black immigrants have the worst hypertension profiles, and Black and Hispanic immigrants have the worst obesity profiles. The results suggest that acculturation cannot fully explain racial-ethnic differences in the association between U.S. tenure and health outcomes. We advance a more complete sociological theory of immigrant integration to better explain disparate immigrant health profiles.

Metabolic syndrome and its association with physical activity in Sudanese early adolescents - Khartoum state, Sudan: An observational study.

The growing prevalence of overweight/obesity in adolescents highlights the significance of studying metabolic syndrome (MetS) in increasingly sedentary adolescents. To date, no study in Sudan has examined the association between MetS and physical activity (PA) among adolescents. This study aimed to assess the association between MetS and its components and PA among Sudanese early adolescents. A cross-sectional assessment was conducted from to 2018 to 2019 on a sample of 921 primary school students from Khartoum State, Republic of Sudan. MetS was defined according to the International Diabetes Federation criteria and a standardized questionnaire was used to assess PA. Metabolic equivalents of task were calculated, and levels of different intensities of PA (tertiles) were identified accordingly. The association between PA and MetS and its components was assessed using a logistic regression model. The participants comprised 388 boys and 533 girls with a mean age of 12.59 ±â€…1.21 years. The prevalence of MetS was significantly higher in subjects in the 1st PA tertile (least active) than in the 2nd and 3rd (most active) tertiles of PA, and this difference was observed in both boys and girls. After adjusting for other study factors, the odds of MetS among adolescents in the 1st PA tertile were 7 times higher than those in the highest PA tertile (adjusted odds ratio = 7.01, 95% confidence interval: 1.48, 32.99). A physically inactive lifestyle was associated with higher odds of MetS and its components, especially waist circumference and triglyceride levels, in Sudanese early adolescents. This study highlights the importance of promoting PA in this age group.

Assessing Nutritional Anemia Among University Students in Jazan, Saudi Arabia: A Public Health Perspective.

Background: Nutritional anemia is a significant public health concern worldwide, particularly affecting young adults and children in Saudi Arabia, where inadequate nutrition is considered a primary contributing factor. This study aims to (i) examine the levels of serum iron, folate, and vitamin B12 in young adult students, with a focus on identifying any deficiencies and their association with anemia; (ii) explore the prevalence of mixed-deficiency anemia resulting from deficiencies in serum iron, folate, and vitamin B12 (iii) explore how sociodemographic characteristics and dietary habits influence serum iron, folate, and vitamin B12 levels. Materials and Methods: This cross-sectional study encompassed 158 young adult students at Jazan University, Saudi Arabia. Blood samples were collected following a comprehensive questionnaire addressing sociodemographic and health characteristics. These samples were analyzed for complete blood count, serum iron, folate, and vitamin B12 levels. Results: The findings of this study revealed a significant decrease in serum iron levels, with 70.6% of males and 88% in females exhibiting reduced level. Additionally, low levels of folate were observed in 4% of the study population, while deficiency in vitamin B12 was found in 2.2% of the study population. However, the simultaneous presence of low serum iron levels along with deficiencies in folate or vitamin B12 was not observed in the study participants. Conclusion: The study indicates that there is a high incidence of low serum iron and ferritin levels among university students in Saudi Arabia, which poses a considerable public health concern. Conversely, the prevalence of folate and vitamin B12 deficiencies among the students was comparatively low, and notably, there were no cases where these deficiencies were observed alongside iron deficiency.

"Plasma cell hepatitis" in liver allografts: identification and characterization of an IgG4-rich cohort.

Plasma cell hepatitis (PCH), also known as "de novo autoimmune" hepatitis, is an increasingly recognized, but suboptimally named and poorly understood, category of late allograft dysfunction strongly resembling autoimmune hepatitis (AIH): They share plasma-cell-rich necro-inflammatory activity on biopsy, autoantibodies and steroid responsiveness, but overlap with rejection is problematic. A retrospective study of clinical, serological, histopathological and IgG4 immunohistological features of PCH (n = 20) in liver allograft recipients, native liver AIH (n = 19) and plasma-cell-rich renal allograft rejection (n = 20) showed: (1) high frequency (44%) of HLA-DR15; (2) less female predominance (p = 0.03) and (3) n = 9/20 PCH recipients showed >25 IgG4+ plasma cells/high-power field (IgG4+ PCH) versus AIH (n = 1/19, p = 0.008) or plasma-cell-rich kidney rejection (n = 2/20, p = 0.03). The IgG4+ PCH (n = 9) subgroup showed lower alanine transaminase (ALT) (p < 0.01) and aspartate transaminase (AST) (p < 0.05) at index biopsy but (a) higher plasma cell number/percentage, (b) more aggressive-appearing portal/periportal and perivenular necro-inflammatory activity and (c) more severe portal/periportal fibrosis than IgG4- PCH (n = 11). Significant demographic, histopathologic and plasma cell phenotype differences between PCH and AIH suggest distinct pathogenic mechanisms for at least the IgG4+ PCH subgroup likely representing an overlap between allo- and auto-immunity. IgG4+ PCH was associated with fibrosis, but also highly responsive to increased immunosuppression.

Rapamycin augments human DC IL-12p70 and IL-27 secretion to promote allogeneic Type 1 polarization modulated by NK cells.

Mammalian target of rapamycin kinase inhibitor (mTORi) rapamycin (RAPA) use in transplantation can lead to inflammatory complications in some patients. Our goal was to better understand how mTORi-exposed human monocyte-derived dendritic cells (DC) stimulated with pro-inflammatory cytokines shape T cell allo-immunity. RAPA-conditioned-DC (RAPA-DC) displayed a more immature phenotype than untreated, control (CTRL)-DC. However, subsequent exposure of RAPA-DC to an inflammatory cytokine cocktail (ICC) plus IFN-γ induced a mature Type-1 promoting phenotype, consisting of elevated HLA-DR and co-stimulatory molecules, augmented IL-12p70 and IL-27 production, but decreased IL-10 secretion compared to CTRL-DC. Co-culture of mature (m)RAPA-DC with allogeneic peripheral blood mononuclear cells resulted in significantly increased Type-1 (IFN-γ) responses by T cells. Moreover, NK cells acted as innate modulators that conveyed activating cell-to-cell contact signals in addition to helper (IFN-γ) and/or regulatory (IL-10) soluble cytokines. We conclude that production of IL12-p70, IL-27 and low IL-10 by RAPA-DC allowed us to elucidate how these cytokines as well as NK-DC interaction shapes T cell allo-immunity. Thus, lack of inhibitory NK cell function during allo-specific T cell activation by human ICC + IFN-γ-stimulated RAPA-DC may represent an unwanted effector mechanism that may underlie RAPA-induced inflammatory events in transplant patients undergoing microbial infection or allograft rejection.

Dietary patterns and their associations with glycemic control among type 2 diabetic patients in Jazan, Saudi Arabia: A cross-sectional study.

Diabetes is an important global health concern. According to the World Health Organization, the Kingdom of Saudi Arabia (KSA) has 2.8 to 4.3 million diabetic patients between the ages of 27 to 60 in the year 2022. Medical nutrition therapy an essential component of diabetes management, helps improve diabetes outcomes by assisting patients in achieving a target glycated hemoglobin (HbA1c) level of <7. This study aimed to describe the pattern of food consumption in the study population and determine its association with glycemic control. This was a cross-sectional study among health facility attendees at the Endocrinology and Diabetes Center (EDC) in Jazan, KSA. A total of 315 patients with type 2 diabetes (T2D) were enrolled using a systematic random sampling technique. Sociodemographic and dietary habit information gathered through face-to-face interviews, anthropometric measurements, and HbA1c were collected from medical records. Participants were mostly females (55.6%), and more than half of them were above 50 years of age. More than 90% of the patients had poor HbA1c levels, and 2-thirds of the patients were overweight and obese (43.8% and 37.1%, respectively). The most consumed foods were bread (8 times/week) and coffee/tea and vegetables (7 times per week), and the least consumed was soda beverages (once/week). Multivariate logistic regression revealed that the consumption of fruits (consumed 5 times/week) significantly decreased HbA1c, while the consumption of pastries/pizza (consumed twice/week) significantly increased it. The pattern of consumption of fruits and vegetables in the study population conformed to the recommended levels, and that of fruits showed a statistically significant association with the control of HbA1c. Another food item that has a significant negative effect on HbA1c is pastries/pizza. Further studies that include more potentially confounding variables, such as treatment type, are needed.

Nano-Emulsion Based Gel for Topical Delivery of an Anti-Inflammatory Drug: In vitro and in vivo Evaluation.

Introduction: Arthritic disorder is a common disease in elderly patients and the most common cause of joint dysfunction. This study aims to design Piroxicam-loaded nanoemulsion (PXM-NE) formulations to enhance the analgesic and anti-inflammatory activity of the drug for topical use. Methods: The nanoemulsion preparations were designed based on a high-pressure homogenization technique and were characterized for particle size (PS), poly dispersity index (Pi), zeta potential (ZP), drug content, and the selected formula was investigated for its topical analgesic activity and pharmacokinetic parameters. Results: The characterizations showed that the PS was 310.20±19.84 nm, Pi was 0.15±0.02, and ZP was -15.74±1.6 mV for the selected formula. A morphology study showed that the PXM-NE droplets were spherical with a uniform size distribution. The in vitro release study showed a biphasic release pattern with a rapid release within the first 2 hours followed by a sustained release pattern. The analgesic activity for optimal formula was 1.66 times higher than the commercial gel with a double duration of analgesic activity. The Cmax was 45.73±9.95 and 28.48±6.44 ng/mL for the gel form of the selected formula and the commercial gel respectively. The relevant bioavailability of the selected formula was 2.41 higher than the commercial gel. Conclusion: The results showed good physicochemical properties, higher bioavailability, and a longer analgesic effect of PXM from nanoemulsion gel, as compared to the commercial product.