Biochemical properties and biological potential of Syzygium heyneanum with antiparkinson's activity in paraquat induced rodent model.

Syzygium heyneanum is a valuable source of flavonoids and phenols, known for their antioxidant and neuroprotective properties. This research aimed to explore the potential of Syzygium heyneanum ethanol extract (SHE) in countering Parkinson's disease. The presence of phenols and flavonoids results in SHE displaying an IC50 value of 42.13 when assessed in the DPPH scavenging assay. Rats' vital organs (lungs, heart, spleen, liver, and kidney) histopathology reveals little or almost no harmful effect. The study hypothesized that SHE possesses antioxidants that could mitigate Parkinson's symptoms by influencing α-synuclein, acetylcholinesterase (AChE), TNF-α, and IL-1ß. Both in silico and in vivo investigations were conducted. The Parkinson's rat model was established using paraquat (1 mg/kg, i.p.), with rats divided into control, disease control, standard, and SHE-treated groups (150, 300, and 600 mg/kg) for 21 days. According to the ELISA statistics, the SHE treated group had lowers levels of IL-6 and TNF-α than the disease control group, which is a sign of neuroprotection. Behavioral and biochemical assessments were performed, alongside mRNA expression analyses using RT-PCR to assess SHE's impact on α-synuclein, AChE, TNF-α, and interleukins in brain homogenates. Behavioral observations demonstrated dose-dependent improvements in rats treated with SHE (600 > 300 > 150 mg/kg). Antioxidant enzyme levels (catalase, superoxide dismutase, glutathione) were significantly restored, particularly at a high dose, with notable reduction in malondialdehyde. The high dose of SHE notably lowered acetylcholinesterase levels. qRT-PCR results indicated reduced mRNA expression of IL-1ß, α-synuclein, TNF-α, and AChE in SHE-treated groups compared to disease controls, suggesting neuroprotection. In conclusion, this study highlights Syzygium heyneanum potential to alleviate Parkinson's disease symptoms through its antioxidant and modulatory effects on relevant biomarkers.

Tocopherol succinate-loaded ethosomal gel synthesized by cold method technique: Deeper biophysical characterizations for translational application on human skin.

BACKGROUND: Tocopherols are well-known antioxidant and moisturizing agent. Tocopherol succinate (TS) are widely used in many skin products especially used in anti-aging and skin whitening product formulation. AIM: We previously reported the successful synthesis and preliminary characterizations of stable TS ethosomal gels (TSEG) (DOI: 10.1111/jocd.14907). Herein, we develop and further characterize TSEG to enhance the stability of the developed formulation with increased permeation through skin. METHODS: Cold method technique was used to prepare TS ethosomes. The developed ethosomal vesicle size was 250 nm, which allowed TS to penetrate through the stratum corneum layer and act on melanocytes. For stability study was assessed by thermogravimetric analysis (TGA) by placing TSEG and unloaded/control ethosomal gel (CEG) at various temperature conditions, that is, 8°C, 25°C, 40°C, and 40°C ± 75% RH for 3 months. Organoleptic evaluation was done in terms of color, odor, and phase separation. Transmission electron microscopy (TEM), Fourier Transform infrared spectroscopy (FTIR), x-ray diffraction spectroscopy (XRD), zeta potential (ZP) and particle size (PS) was used for TSEG physical characterizations. In vitro dissolution and ex-vivo permeation studies (using Franz diffusion cell) were performed for both TSEG and CEG formulations. Human women (N = 34) were used to evaluate in vivo biophysical parameters including erythema, melanin, moisture content, sebum level, and skin elasticity. RESULTS: Developed formulation was highly thermostable during the 3 months. Erythema, melanin, and sebum level decreased while marked improvement (p < 0.05) in moisture content and elasticity have been observed for the developed TSEG. CONCLUSION: The developed TSEG formulation was found to be efficient, safe (no adverse effects observed), stable (at least for 3 months), and easy to use for topical application with improved skin complexation and skin integrity.

Dermatologic conditions of adult refugees following resettlement in the United States, 2015 to 2018.

Background: There is a paucity of literature regarding dermatologic conditions in migrant and refugee populations. Methods: We conducted a cross-sectional study of all adult refugees resettling in a region of Connecticut, U.S. from 7 January 2015 to 20 November 2018. We conducted a manual chart review to determine dermatologic conditions diagnosed during and within one year of resettlement. We used multivariable logistic regression to determine demographic and clinical factors associated with having any dermatologic condition. Results: We included 545 refugees primarily from Afghanistan (40.6%), Syria (24.6%) and Iraq (10.5%), with a median (interquartile range) age of 33 (28-40) years. Of the 545 participants, 213 (39.1%) had dermatologic conditions. Fifty-four participants (25%) had more than one dermatologic condition and 114 (53.5%) were diagnosed within the first month of resettlement. The most common categories of conditions were cutaneous infections (24.9%), inflammatory conditions (11.1%), and scar or burn (10.7%). Tobacco use was associated with having a cutaneous infection (OR 2.37, 95%CI:1.09-4.95), and younger age was associated with having a scar or burn (for each year increase in age, OR 0.95, 95%CI:0.91-0.99). Conclusion: Dermatologic conditions are common among adult refugees. The majority of conditions were diagnosed in the first month following resettlement suggesting that a high number of dermatologic conditions arise or go undetected and untreated during the migration process.

Evaluation of Low Molecular Weight Cross Linked Chitosan Nanoparticles, to Enhance the Bioavailability of 5-Flourouracil.

The present study aimed to formulate 5-fluorouracil loaded cross linked chitosan nanoparticles based on chemical cross-linking of low molecular weight chitosan with glutaraldehyde by reverse micelles technique as 5-FU is less hydrophobic, relatively potent, has a shorter half-life, is rapidly metabolized, less tolerated, and has low oral bioavailability; therefore, we aimed to formulate potential nanocarriers of 5-FU for efficient drug delivery to specific targeted areas of action, reduce oral toxicity, improve tolerability and therapeutic outcomes of 5-FU, in a restricted fashion to enhance the bioavailability of 5-FU. Nanoparticles were formulated by the reverse micelle method based on the chemical cross-linking of glutaraldehyde (25% aqueous solution) into a w/o emulsion in different ratios. LMWCH-NPs were characterized for post-formulation parameters by mean particle size, zeta potential, %age yield, loading/entrapment efficiency, Fourier transform infrared spectroscopy (FTIR), DSC/TGA, TEM, PXRD, drug release at pH 1.2, and pH 7.4. 5-FU loaded NPs showed a size range (198 nm-200 nm) and zeta potential (-39mV to -41mV), which ensured mechanical stability and increased retention time in blood vessels by the sustained release properties of biodegradable nanocarrier drug delivery systems. % age yield showed the range 92% to 96% while % LC ranged 2.0% to 3.4% and %EE ranged 40% to 43%. The TEM images showed spherical nanoparticles. FTIR revealed the compatibility between the drug and the cross-linked polymer. DSC/TGA ensured the thermal stability of the drug, while the solid-state stability of the drug-loaded cross-linked chitosan nanoparticles was evaluated by powder X-ray diffraction (PXRD) analysis. Drug release studies were performed using the dialysis bag technique at both pH (1.2 and 7.4) to mimic the gastrointestinal tract. Highly stable NPs displayed targeted release in phosphate buffer pH 7.4 at 37°C. Fickian diffusion was the predominant release with an R2 value of 0.9975-0.9973-and an N value 0.45-0.53. Prepared nanoparticles are inert, biodegradable, and biocompatible drug delivery systems for sustained release of 5-FU with maximum therapeutic efficacy and bioavailability.

Pharmacokinetic variables of medium molecular weight cross linked chitosan nanoparticles to enhance the bioavailability of 5-fluorouracil and reduce the acute oral toxicity.

To prepare glutaraldehyde-based cross-linked medium molecular weight chitosan nanoparticles encapsulated with 5-Fluorouracil (5-FU), to overcome dosing frequency as well as reducing acute oral toxicity and poor bioavailability of the drug. Medium molecular weight chitosan nanoparticles (MMWCH-NPs) were prepared by reverse micelles method based on glutaraldehyde (GA) cross-linking and optimized by the process as well as formulation variables like a various drug to polymer ratio, cross-linker volumes, varying stirring speeds (rpm), different time of rotation/stirring, respectively and their effects on the mean particles size distribution and entrapment efficiency %EE and %LC of NPs. Characterization of formulations was done by FTIR studies, TEM, PXRD, TGA, Stability, and dissolution drug release studies were performed by dialysis bag technique at both pH (1.2 & 7.4) and acute oral toxicity studies in albino rabbits. The formulated nanoparticles showed a smooth morphology with smaller particle size distribution (230-550 nm), zeta potential (-15 to -18 mV) required to achieve enhanced permeation and retention effect (EPR), entrapment efficiency (%EE 12-59%). These NPs exhibited a controlled drug release profile with 84.36% of the drug over a period of 24 h. Drug release data were fitted to different kinetic models which predominantly followed Fickian diffusion mechanism (R2 = 0.972-0.976, N = 0.326-0.256). The optimized formulation (5-FU6) was observed under DSC/TGA, TEM. PXRD curves, FTIR, which confirmed thermal stability, structural integrity, amorphous state, compatibility between drug and polymer of optimized (5-FU6) as well as reduced acute oral toxicity in albino rabbits. Cross-linked medium molecular weight chitosan nanoparticles are nontoxic, well-tolerated therefore could be the future candidate for therapeutic effects as novel drug delivery carrier for anticancer drug(s).

Dermatologic manifestations of COVID-19: a comprehensive systematic review.

Recent reports have suggested that there may be dermatologic manifestations of COVID-19. We searched 12 databases for peer-reviewed or pre-print published studies until July 15, 2020, for this PRISMA-compliant review (CRD42020182050). We used the Oxford Center for Evidence-Based Medicine Levels of Evidence to facilitate data synthesis. From 86 retrieved studies, we collated data on 2,560 patients with dermatologic manifestations of COVID-19. The most common findings were chilblains/pernio-like lesion (51.5%), erythematous maculopapular rashes (13.3%), and viral exanthem (7.7%). Average pediatric age was 12.9 years (SD 3.6) and adult was 34.2 years (SD 21.8). Average latency from time of upper respiratory illness symptoms to cutaneous findings was 1.5 days (SD 2.9) in children and 7.9 days (SD 10.7) in adults, ranging from -3 to 38 days. Roughly one-tenth in both populations were otherwise asymptomatic or presented with only skin findings for the entirety of the disease course; 13.3% (pediatrics) and 5.3% (adults) presented with skin issues first. Dermatologic findings may play an important role in identifying cases early and serve as an important proxy to manage spread. Further prospective data collection with international prospective registries is needed.

A Deep Learning Convolutional Neural Network Can Recognize Common Patterns of Injury in Gastric Pathology.

CONTEXT.­: Most deep learning (DL) studies have focused on neoplastic pathology, with the realm of inflammatory pathology remaining largely untouched. OBJECTIVE.­: To investigate the use of DL for nonneoplastic gastric biopsies. DESIGN.­: Gold standard diagnoses were blindly established by 2 gastrointestinal pathologists. For phase 1, 300 classic cases (100 normal, 100 Helicobacter pylori, 100 reactive gastropathy) that best displayed the desired pathology were scanned and annotated for DL analysis. A total of 70% of the cases for each group were selected for the training set, and 30% were included in the test set. The software assigned colored labels to the test biopsies, which corresponded to the area of the tissue assigned a diagnosis by the DL algorithm, termed area distribution (AD). For Phase 2, an additional 106 consecutive nonclassical gastric biopsies from our archives were tested in the same fashion. RESULTS.­: For Phase 1, receiver operating curves showed near perfect agreement with the gold standard diagnoses at an AD percentage cutoff of 50% for normal (area under the curve [AUC] = 99.7%) and H pylori (AUC = 100%), and 40% for reactive gastropathy (AUC = 99.9%). Sensitivity/specificity pairings were as follows: normal (96.7%, 86.7%), H pylori (100%, 98.3%), and reactive gastropathy (96.7%, 96.7%). For phase 2, receiver operating curves were slightly less discriminatory, with optimal AD cutoffs reduced to 40% across diagnostic groups. The AUCs were 91.9% for normal, 100% for H pylori, and 94.0% for reactive gastropathy. Sensitivity/specificity parings were as follows: normal (73.7%, 79.6%), H pylori (95.7%, 100%), reactive gastropathy (100%, 62.5%). CONCLUSIONS.­: A convolutional neural network can serve as an effective screening tool/diagnostic aid for H pylori gastritis.

Health needs of refugees: port of arrival versus permanent camp settings.

BACKGROUND: The world's refugee population has surpassed 21 million, the large majority of which resides in developing countries. Refugees have relatively high rates of healthcare utilization for management of both long-term needs, such as diabetes, and acute conditions, such as scabies. AIMS: Using interviews of stakeholders in disparate healthcare settings, we aim to elucidate both common themes and areas of difference that should be recognized and addressed as the refugee crisis continues. METHODS: This qualitative interview study compares and contrasts two settings for healthcare provision for refugees: the permanent setting of Za'atari, a camp in Jordan, versus the transitory arrival location of Lampedusa, Italy. RESULTS: We present data from 12 semi-structured interviews with experts in refugee healthcare that have experience in these two locations. We focus on issues of disease burden and health screening, organizational structures and services, cultural competency, and international response. CONCLUSIONS: We compiled recommendations to improve healthcare for refugees include recognizing differing health needs of refugees in Za'atari and Lampedusa, training providers in culturally-competent care, screening for and treating psychiatric disorders, and prioritizing agency coordination, documentation, and advocacy.

High molecular weight cross linked chitosan nanoparticles for controlled release of 5-Fluorouracil; Enhances its bioavailability.

The aim of study was cross linking of high molecular weight chitosan nanoparticles containing 5-fluorouracil to improve dissolution rate and ultimately enhance its bioavailability by reverse emulsion/micelles method and cross-linking agent i.e. glutaraldehyde (GA 25% aqueous solution in water). The nature and outer morphologies were evaluated by scanning electron microscopy (SEM). Drug release models were functional to support way from cross linked NPs. Cross linking of 5-fluorouracil with glutaraldehyde improved dissolution rate. Mean dissolution time of 5-fluorouracil decreased significantly upon reverse emulsion/cross linking as encapsulated drug is protective and thermally stable within cross linked chitosan NPs. FTIR studies showed formation of intermolecular hydrogen bonding between 5-fluorouracil and GA-co-CHNPs. DSC studies indicated a less crystalline state of 5-fluorouracil in cross linking. SEM showed spherical nanoparticles with somewhat rough surface. 5-FU release followed Korsmeyer-Peppas model which indicate diffusion and dissociation control drug release from GA-co-CH-NPs. 5-FU cross linked chitosan nanoparticles can be safe and useful tool for other chemotherapeutic agents.

Role of Immune Status in Chemotherapy-Induced Transient Acantholytic Dermatosis.

A 79-year-old man with a recent diagnosis of acute myeloblastic leukemia received induction chemotherapy with daunorubicin and cytarabine, plus moxifloxacin and fluconazole prophylaxis. Approximately 2 weeks later, an asymptomatic eruption appeared on his trunk. He then developed a neutropenic fever and was started on aztreonam, vancomycin, voriconazole, and amikacin and was transferred to our facility from an outside hospital. Micafungin was subsequently added, and the patient defervesced within a few days.

Mucocutaneous manifestations of helminth infections: Nematodes.

In the 21st century, despite increased globalization through international travel for business, medical volunteerism, pleasure, and immigration/refugees into the United States, there is little published in the dermatology literature regarding the cutaneous manifestations of helminth infections. Approximately 17% of travelers seek medical care because of cutaneous disorders, many related to infectious etiologies. This review will focus on the cutaneous manifestations of helminth infections and is divided into 2 parts: part I focuses on nematode infections, and part II focuses on trematode and cestode infections. This review highlights the clinical manifestations, transmission, diagnosis, and treatment of helminth infections. Nematodes are roundworms that cause diseases with cutaneous manifestations, such as cutaneous larval migrans, onchocerciasis, filariasis, gnathostomiasis, loiasis, dracunculiasis, strongyloidiasis, ascariasis, streptocerciasis, dirofilariasis, and trichinosis. Tremadotes, also known as flukes, cause schistosomiasis, paragonimiasis, and fascioliasis. Cestodes (tapeworms) are flat, hermaphroditic parasites that cause diseases such as sparganosis, cysticercosis, and echinococcus.

A morphologic reappraisal of endoscopically but not histologically apparent polyps and the emergence of the overlooked goblet cell--rich hyperplastic polyp.

Goblet cell--rich hyperplastic polyps (GCRHP) are morphologically subtle compared to microvesicular hyperplastic polyps (MVHP) and are believed to be the most commonly unrecognized serrated polyp, though this has not been systematically studied. We hypothesize that a gastrointestinal pathologist's review of endoscopically but not histologically apparent polyps will identify previously missed GCRHPs, a finding that may be clinically significant if the addition of this subtype of serrated polyp contributes to sufficient numeric criteria for a clinical diagnosis of serrated polyposis syndrome (SPS). Two blinded reviews were performed on 160 endoscopically but not histologically apparent polyps by a gastrointestinal pathologist, separated by a 6 month "washout period." A final review diagnosis of GCRHP was applied to all polyps with complete agreement on both reviews. Patient records were then searched to determine if the addition of a GCRHP resulted in sufficient numeric criteria for a clinical diagnosis of SPS. Fourteen (9%) polyps were reclassified as GCRHPs. The majority (n = 12, 86%) were originally called "colonic mucosa with surface hyperplastic change (CMWSHC)." Two polyps (1%) were re-classified as MVHPs. No other serrated or adenomatous polyps were identified. For each patient, the addition of a hyperplastic polyp did not result in a clinical diagnosis of SPS, though one patient fell short of this diagnosis by only one polyp. GCRHPs are the most commonly underdiagnosed serrated polyp and are often called CMWSHC. The addition of previously missed GCRHPs is unlikely to contribute to a diagnosis of SPS in an individual patient.

Performing colonic mast cell counts in patients with chronic diarrhea of unknown etiology has limited diagnostic use.

CONTEXT: Mastocytic enterocolitis is a recently described entity defined by chronic diarrhea of unknown etiology and normal colon biopsy results with increased mast cells (MCs) seen on special stains. These patients may benefit from mast cell stabilizers; however, the clinical utility of MC counts remains unknown. OBJECTIVE: To determine the clinical utility of colonic MC counts on normal biopsies in patients with chronic diarrhea of unknown etiology. DESIGN: Blinded MC counts using a c-Kit stain were performed in 76 consecutive patients with chronic diarrhea of unknown etiology who had normal colon biopsy results and in 89 consecutive control patients presenting for screening colonoscopy. Mast cells were counted per single high-power field in the highest-density area. A t test was used to compare the counts, and receiver operating characteristic curves were generated to examine sensitive and specific cutoff values. RESULTS: Overall, MC counts averaged 31 MCs per high-power field in the study group versus 24 MCs per high-power field in the control group (P < .001). When stratified by location, a significant increase was seen in biopsies from the left colon only. Receiver operating characteristic analysis revealed that overall MC counts, left-sided MC counts, and the difference between right- and left-sided MC counts did not yield discriminatory cutoff values (area under the curve, 0.68, 0.74, and 0.81, respectively). CONCLUSIONS: Mast cell counts were increased in patients with chronic diarrhea of unknown etiology, primarily in the left colon. However, receiver operating characteristic analysis demonstrates no discriminatory cutoff values. Quantitative MC stains yield little useful diagnostic information, and further studies are necessary to determine whether mastocytic enterocolitis truly represents a distinct entity.

Guidelines on the role of skin care in the management of mobile populations.

The Task Force for Skin Care for All: Community Dermatology, when seeking to collate evidence for capacity to benefit, wanted to know how best to manage mobile populations. The task force met where there is most experience at a time of maximum migration to the Mediterranean islands and to Italy from Somalia, Sudan, Cote d'Ivoire, Tunisia, and Libya. Members attended the workshop hosted by Aldo Morrone at the San Gallicano Hospital, Rome, Italy. Issues discussed were the size of the problem, ethics and legality, potential value of the migrant, dermatologist as carer, challenges met by interpretation, good listening, and transcultural mediation. The experiences of the National Institute for Health Migration and Poverty at the San Gallicano Hospital in Rome, Ethiopia, Malta, and Lampedusa were key to the development of guidelines on cultural competence.

Pityriasis rosea-like drug eruption due to nortriptyline in a patient with vulvodynia.

BACKGROUND: Nortriptyline and other tricyclic antidepressants are widely used in the treatment of depression. They are also used in chronic pain syndromes such as vulvodynia. We report a case of pityriasis rosea (PR)-like eruption in a young woman who was treated with oral nortriptyline for vulvodynia. CASE REPORT: The patient presented with photosensitivity and erythematous, well-defined, oval papules and patches, with fine collarettes of scale on the dorsal hands, upper arms, and trunk. She showed a complete resolution of her rash with discontinuation of nortriptyline, thereby supporting the diagnosis of a drug-induced reaction. COMMENT: Pityriasis rosea-like drug eruptions have been associated with numerous medications, including angiotensin-converting enzyme inhibitors, antirheumatic drugs, lithium, and, more recently, biologics such as imatinib, adalimumab, and etanercept. A literature review did not reveal an association between PR-like drug eruptions and tricyclic antidepressants such as nortriptyline. We report a case of PR-like drug reaction to nortriptyline for clinical interest.

Trypanosoma cruzi infection: a review with emphasis on cutaneous manifestations.

Chagas disease, an infection caused by the protozoan Trypanosoma cruzi and transmitted by the Reduuvid insect vector, remains a major cause of morbidity in Central and South America over a century after its discovery in 1909. Though major advances in preventing the spread of this disease have been made in recent decades, millions of individuals remain chronically infected due to prior exposure to T. cruzi and are at risk for future complications from the disease. Dermatologic manifestations of acute infection may include localized swelling at the site of inoculation (chagoma), conjunctivitis (Romaña's sign), and a generalized morbilliform eruption (schizotrypanides). Reactivation of quiescent infection in immunocompromised hosts due to the acquired immunodeficiency syndrome or organ transplantation can present with fever and skin lesions including panniculitis. The widespread emigration of chronic carriers of T. cruzi to North America, Europe, and Australia makes it imperative that dermatologists worldwide be familiar with this entity to ensure proper diagnosis and treatment.

Dermatology and HIV/AIDS in Africa.

Human immunodeficiency virus and the acquired immunodeficiency syndrome (HIV/AIDS) have greatly complicated dermatologic disease and the required care in most regions of Africa. Opportunistic infections, ectoparasites, Kaposi sarcoma, and skin manifestations of systemic infections are exceedingly common in patients with HIV/AIDS. Dermatologists have contributed significantly to our knowledge base about HIV/AIDS and have played an important educational role regarding the clinical manifestations historically. Because of the increased burden of skin disease in Africa due to the HIV/AIDS epidemic we must redouble our efforts to provide dermatology education to care providers in Africa. We review the burden of skin disease in Africa, how it relates to HIV/AIDS and global infectious disease, current educational strategies in Africa to address this need, and suggest potential solutions to move these efforts forward.