IV Diuresis in Alternative Treatment Settings for the Management of Heart Failure: Implications for Mortality, Hospitalizations and Cost.

BACKGROUND: Recent advances in heart failure (HF) care have sought to shift management from inpatient to outpatient and observation settings. We evaluated the association among HF treatment in the (1) inpatient; (2) observation; (3) emergency department (ED); and (4) outpatient settings with 30-day mortality, hospitalizations and cost. METHODS: Using 100% Medicare inpatient, outpatient and Part B files from 2011-2018, 1,534,708 unique patient encounters in which intravenous (IV) diuretics were received for a primary diagnosis of HF were identified. Encounters were sorted into mutually exclusive settings: (1) inpatient; (2) observation; (3) ED; or (4) outpatient IV diuretic clinic. The primary outcome was 30-day all-cause mortality. Secondary outcomes included 30-day hospitalization and total 30-day costs. Multivariable logistic and linear regression were used to examine the association between treatment location and the primary and secondary outcomes. RESULTS: Patients treated in observation and outpatient settings had lower 30-day mortality rates (observation OR 0.67, 95% CI 0.66-0.69; P < 0.001; outpatient OR 0.53, 95% CI 0.51-0.55; P < 0.001) compared to those treated in inpatient settings. Observation and outpatient treatment were also associated with decreased 30-day total cost compared to inpatient treatment. Observation relative cost -$5528.77, 95% CI -$5613.63 to -$5443.92; outpatient relative cost -$7005.95; 95% CI -$7103.94 to -$6907.96). Patients treated in the emergency department and discharged had increased mortality rates (OR 1.15, 95% CI 1.13-1.17; P < 0.001) and increased rates of hospitalization (OR 1.72, 95% CI 1.70-1.73; P < 0.001) compared to patients treated as inpatients. CONCLUSIONS: Medicare beneficiaries who received IV diuresis for acute HF in the outpatient and observation settings had lower mortality rates and decreased costs of care compared to patients treated as inpatients. Outpatient and observation management of acute decompensated HF, when available, is a safe and cost-effective strategy in certain populations of patients with HF.

Nocturnal vestibular stimulation using a rocking bed improves a severe sleep disorder in a patient with mitochondrial disease.

Mitochondrial diseases are rare genetic disorders often accompanied by severe sleep disorders. We present the case of a 12-year-old boy diagnosed with a severe primary mitochondrial disease, exhibiting ataxia, spasticity, progressive external ophthalmoplegia, cardiomyopathy and severely disrupted sleep, but no cognitive impairment. Interestingly, his parents reported improved sleep during night train rides. Based on this observation, we installed a rocking bed in the patient's bedroom and performed different interventions, including immersive multimodal vestibular, kinesthetic and auditory stimuli, reminiscent of the sensory experiences encountered during train rides. Over a 5-month period, we conducted four 2-week nocturnal interventions, separated by 1-week washout phases, to determine the subjectively best-perceived stimulation parameters, followed by a final 4-week intervention using the optimal parameters. We assessed sleep duration and quality using the Mini Sleep Questionnaire, monitored pulse rate changes and used videography to document nocturnal interactions between the patient and caregivers. Patient-reported outcome measures, clinical examinations and personal outcomes of specific interests were used to document daytime sleepiness, restlessness, anxiety, fatigue, cognitive performance and physical posture. In the final 4-week intervention, sleep duration increased by 25%, required caregiver interactions reduced by 75%, and caregiving time decreased by 40%. Subjective fatigue, assessed by the Checklist Individual Strength, decreased by 40%, falling below the threshold of severe fatigue. Our study suggests that rocking beds could provide a promising treatment regime for selected patients with persistent severe sleep disorders. Further research is required to validate these findings in larger patient populations with sleep disorders and other conditions.

Antifungal potential of the new copper(II)-theophylline/1,10-phenanthroline complex against drug-resistant Candida species.

Candida spp. are the commonest fungal pathogens worldwide. Antifungal resistance is a problem that has prompted the discovery of novel anti-Candida drugs. Herein, 25 compounds, some of them containing copper(II), cobalt(II) and manganese(II) ions, were initially evaluated for inhibiting the growth of reference strains of Candida albicans and Candida tropicalis. Eight (32%) of the compounds inhibited the proliferation of these yeasts, displaying minimum inhibitory concentrations (MICs) ranging from 31.25 to 250 µg/mL and minimum fungicidal concentration (MFCs) from 62.5 to 250 µg/mL. Drug-likeness/pharmacokinetic calculated by SwissADME indicated that the 8 selected compounds were suitable for use as topical drugs. The complex CTP, Cu(theo)2phen(H2O).5H2O (theo = theophylline; phen = 1,10-phenanthroline), was chosen for further testing against 10 medically relevant Candida species that were resistant to fluconazole/amphotericin B. CTP demonstrated a broad spectrum of action, inhibiting the growth of all 20 clinical fungal isolates, with MICs from 7.81 to 62.5 µg/mL and MFCs from 15.62 to 62.5 µg/mL. Conversely, CTP did not cause lysis in erythrocytes. The toxicity of CTP was evaluated in vivo using Galleria mellonella and Tenebrio molitor. CTP had no or low levels of toxicity at doses ranging from 31.25 to 250 µg/mL for 5 days. After 24 h of treatment, G. mellonella larvae exhibited high survival rates even when exposed to high doses of CTP (600 µg/mL), with the 50% cytotoxic concentration calculated as 776.2 µg/mL, generating selectivity indexes varying from 12.4 to 99.4 depending on each Candida species. These findings suggest that CTP could serve as a potential drug to treat infections caused by Candida species resistant to clinically available antifungals.

Unveiling the antifungal mechanisms of CTP, a new copper(II)-theophylline/1,10-phenanthroline complex, on drug-resistant non-albicans Candida species.

Candida species undeniably rank as the most prevalent opportunistic human fungal pathogens worldwide, with Candida albicans as the predominant representative. However, the emergence of non-albicans Candida species (NACs) has marked a significant shift, accompanied by rising incidence rates and concerning trends of antifungal resistance. The search for new strategies to combat antifungal-resistant Candida strains is of paramount importance. Recently, our research group reported the anti-Candida activity of a coordination compound containing copper(II) complexed with theophylline (theo) and 1,10-phenanthroline (phen), known as "CTP" - Cu(theo)2phen(H2O).5H2O. In the present work, we investigated the mechanisms of action of CTP against six medically relevant, antifungal-resistant NACs, including C. auris, C. glabrata, C. haemulonii, C. krusei, C. parapsilosis and C. tropicalis. CTP demonstrated significant efficacy in inhibiting mitochondrial dehydrogenases, leading to heightened intracellular reactive oxygen species production. CTP treatment resulted in substantial damage to the plasma membrane, as evidenced by the passive incorporation of propidium iodide, and induced DNA fragmentation as revealed by the TUNEL assay. Scanning electron microscopy images of post-CTP treatment NACs further illustrated profound alterations in the fungal surface morphology, including invaginations, cavitations and lysis. These surface modifications significantly impacted the ability of Candida cells to adhere to a polystyrene surface and to form robust biofilm structures. Moreover, CTP was effective in disassembling mature biofilms formed by these NACs. In conclusion, CTP represents a promising avenue for the development of novel antifungals with innovative mechanisms of action against clinically relevant NACs that are resistant to antifungals commonly used in clinical settings.

Unauthentic Information About Celiac Disease on Social Networking Pages: Is It a Matter of Concern in Celiac Disease Management?

BACKGROUND: Facebook (FB) is the most popular online networking platform. Many celiac disease Facebook (CD-FB) pages spread awareness about celiac disease (CD). To get the latest information, patients with CD frequently follow such pages. However, little is known about whether such pages provide authentic and reliable information. AIMS: This study aims to investigate whether CD-FB pages spread misleading information to patients with CD. METHODS: On the Facebook social networking platform, CD-FB pages created in three celiac-prevalent countries (Italy, the USA, and India) were explored using different combinations of keywords. The type/category of the CD-FB page, country of origin, purpose, page web link, and number of followers/members were documented in a Microsoft spreadsheet. All posts distributed on selected CD-FB pages in the last 3 years were thoroughly screened. RESULTS: From August 2022 to March 2023, a total of 200 CD-FB pages from Italy, the USA, and India were explored. Out of these 200 pages, 155 CD-FB (Italy 70; the USA 46; India 39) were found eligible. Of them, 20 (13%) CD-FB pages (Italy 4; the USA 5; India 11) shared misleading information about CD. Surprisingly, 11 (8%) of these 20 pages (Italy 0; the USA 2; India 9) supported alternative treatment options for CD. CONCLUSIONS: CD-FB pages are useful for disseminating celiac-disease-related information. While most such pages provide useful information, 13% of CD-FB pages allow misleading information. Patients with CD should consult their treating unit before following any uncertain information posted on CD-FB pages.

Comparison of the effect of phenobarbital & levetiracetam in the treatment of neonatal abstinence syndrome (NAS) as adjuvant treatment in neonates admitted to the neonatal intensive care unit: a randomized clinical trial.

BACKGROUND: Infants who are born from mothers with substance use disorder might suffer from neonatal abstinence syndrome (NAS) and need treatment with medicines. One of these medicines is phenobarbital, which may cause side effects in long-term consumption. Alternative drugs can be used to reduce these side effects. This study seeks the comparison of the effects of phenobarbital & levetiracetam as adjuvant therapy in neonatal abstinence syndrome. METHODS: This randomized clinical trial was performed in one year from May 2021 until May 2022. The neonates who were born from mothers with substance use disorder and had neonatal abstinence syndrome in Afzalipoor Hospital of Kerman were studied. The treatment started with morphine initially and every four hours the infants were checked. The infants who were diagnosed with uncontrolled symptoms After obtaining informed consent from the parents were randomly divided into two groups and treated with secondary drugs, either phenobarbital or levetiracetam. RESULTS: Based on the obtained results, it was clear that there was no significant difference between the hospitalization time of the two infant groups under therapy (phenobarbital: 18.59 days versus Levetiracetam 18.24 days) (P-value = 0.512). Also, there was no significant difference between both groups in terms of the frequency of re-hospitalization during the first week after discharge, the occurrence of complications, and third treatment line prescription (P-value = 0.644). CONCLUSIONS: Based on the obtained results, like hospitalization duration time (P-value = 0.512) it seems that levetiracetam can be used to substitute phenobarbital in treating neonatal abstinence syndrome. TRIAL REGISTRATION: The current study has been registered in the Iran registry of clinical trials website (fa.irct.ir) on the date 25/2/2022 with registration no. IRCT20211218053444N2.

Re-Purposing FDA-Approved Drugs for Opioid Use Disorder.

OBJECTIVE: To investigate FDA-approved drugs prescribed for unrelated diseases or conditions that promote remission in subjects diagnosed with opioid use disorder (OUD). METHODS: This was a retrospective observational study utilizing the TriNetX electronic medical record data. Subjects between 18 and 65 years old were included in this study. First, a drug screen was employed to identify medications used for chronic illness that are associated with OUD remission. Based on Fisher's exact test for significance, 28 of 101 medications were selected for further analysis. Positive (buprenorphine/methadone) and negative controls (benazepril) were included in the analysis. Medications were analyzed in the absence and presence of buprenorphine or methadone, two medications used to treat OUD, to identify the likelihood of OUD remission up to one year following the index event. RESULTS: We identify 8 medications (prazosin, propranolol, lithium carbonate, olanzapine, quetiapine, bupropion, citalopram, and escitalopram) that may be useful for increasing remission in OUD in the absence of buprenorphine or methadone. Additionally, our results identify psychiatric medications that when taken alongside buprenorphine and methadone improve remission rates. CONCLUSION: These results provide medication options that may be useful in treating OUD as well as integrated therapies to treat comorbid mental illness.

Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options.

Urinary tract infections (UTIs) are common bacterial infections that represent a severe public health problem. They are often caused by Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumonia), Proteus mirabilis (P. mirabilis), Enterococcus faecalis (E. faecalis), and Staphylococcus saprophyticus (S. saprophyticus). Among these, uropathogenic E. coli (UPEC) are the most common causative agent in both uncomplicated and complicated UTIs. The adaptive evolution of UPEC has been observed in several ways, including changes in colonization, attachment, invasion, and intracellular replication to invade the urothelium and survive intracellularly. While antibiotic therapy has historically been very successful in controlling UTIs, high recurrence rates and increasing antimicrobial resistance among uropathogens threaten to greatly reduce the efficacy of these treatments. Furthermore, the gradual global emergence of multidrug-resistant UPEC has highlighted the need to further explore its pathogenesis and seek alternative therapeutic and preventative strategies. Therefore, a thorough understanding of the clinical status and pathogenesis of UTIs and the advantages and disadvantages of antibiotics as a conventional treatment option could spark a surge in the search for alternative treatment options, especially vaccines and medicinal plants. Such options targeting multiple pathogenic mechanisms of UPEC are expected to be a focus of UTI management in the future to help combat antibiotic resistance.

Isolation and evaluation of the efficacy of bacteriophages against multidrug-resistant (MDR), methicillin-resistant (MRSA) and biofilm-producing strains of Staphylococcus aureus recovered from bovine mastitis.

BACKGROUND: Staphylococcus aureus (S. aureus) is one of the major causes of bovine mastitis with significant economic losses around the worldwide. The emergence of multidrug-resistant (MDR), methicillin-resistant (MRSA) and biofilm-producing strains of S. aureus challenges the treatment strategies based on the antibiotic application. Today, alternative or combinational treatment options such as bacteriophage application has received much attention. The goal of the present study was to focus on isolation and evaluation of the efficacy of bacteriophages with specific lytic activity against S. aureus strains with low cure rates (MDR, MRSA and biofilm-producing strains). RESULTS: In the present study, two phages belonging to the Podoviridae family with specific lytic activity against S. aureus were isolated from the sewage of dairy farms and designated as Staphylococcus phage M8 and Staphylococcus phage B4. Latent period and burst size for Staphylococcus phage M8 (70 min, 72 PFU/cell) and Staphylococcus phage B4 (30 min, 447 PFU/cell) were also defined. Our results revealed the susceptibility of MDR (4/20; 20%), MRSA (4/13; 30.8%) and biofilm-producing (1/10; 10%) strains to Staphylococcus phage M8. Moreover, one biofilm-producing strain (1/10; 10%) was susceptible to Staphylococcus phage B4. Furthermore, both phages kept their lytic activity in milk. They reduced the S. aureus population by about 3 logs in cultured milk after 8 h of incubation. CONCLUSION: In conclusion, it seems that both phages had the potential to serve as biological control agents alone or in combination with other agents such as antibiotics against infections induced by S. aureus. However, further studies are needed to investigate the efficacy of these phages in vivo.

Phytochemicals and Biological Activities of Burdock (Arctium lappa L.) Extracts: A Review.

Arctium lappa L., also known as burdock, is an edible wild plant which has the ability to grow in distinct environments and is considered a weed in several parts of the world. This species has great value in the biological and medical fields with its major secondary components being phenolic compounds and terpenes, substances rich in desired biological activities as antioxidant, antimicrobial, antitumor and anti-inflammatory. In addition, burdock leaves extracts have shown a modulatory effect on the complement system, which plays an important role in the development of inflammatory diseases, with an inhibitory effect on all complement pathways. Thus, natural products with those relevant activities are promising agents for healthcare applications. Therefore, the species A. lappa may represent an interesting asset for researching and developing new therapies for inflammatory afflictions.

The antimicrobial effect of Rosmarinus officinalis extracts on oral initial adhesion ex vivo.

OBJECTIVE: In the last few decades, there has been a growing worldwide interest in the use of plant extracts for the prevention of oral diseases. The main focus of this interest lies in the identification and isolation of substances that limit the formation of microbial biofilm which plays a major role in the development of caries, periodontitis, and peri-implantitis. In this clinical ex vivo study, we investigated the antimicrobial effects of Rosmarinus officinalis extract against oral microorganisms within in situ initial oral biofilms. MATERIALS AND METHODS: Initial in situ biofilm samples (2 h) from six healthy volunteers were treated ex vivo with R. officinalis extract at concentrations of 20 mg/ml and 30 mg/ml. The number of viable bacterial cells was determined by counting the colony-forming units. All surviving bacteria were isolated in pure cultures and identified using MALDI-TOF and biochemical testing procedures. Additionally, live/dead staining in combination with epifluorescence microscopy was used for visualizing the antimicrobial effects in the initial biofilms. RESULTS: The number of colony-forming units in the R. officinalis-treated biofilms was significantly lower than in the untreated controls (p < 0.001). The reduction range of log10 was 1.64-2.78 and 2.41-3.23 for aerobic and anaerobic bacteria, respectively. Regarding the bacterial composition, large intra- and interindividual variability were observed. Except for Campylobacter spp., the average amount of all bacterial taxa was lower after treatment with R. officinalis than in the untreated biofilms. A total of 49 different species were detected in the untreated biofilms, while only 11 bacterial species were detected in the R. officinalis-treated biofilms. Live/dead staining confirmed that the R. officinalis-treated biofilms had significantly lower numbers of surviving bacteria than the untreated biofilms. CONCLUSIONS: The treatment with R. officinalis extract has a significant potential to eliminate microbial oral initial biofilms. CLINICAL RELEVANCE: The results of this study encourage the use of R. officinalis extracts in biofilm control and thus in the treatment of caries and periodontitis as a herbal adjuvant to synthetic substances.

Alternative Treatment for Erectile Dysfunction: a Growing Arsenal in Men's Health.

PURPOSE OF REVIEW: To highlight and review encouraging preliminary studies behind several alternative products and interventions for erectile dysfunction (ED). RECENT FINDINGS: Alternative treatments for ED are becoming more prevalent with increased consumer interest. "Natural" products are sold online, and numerous clinics offer various off-label and investigational interventions. These alternative treatments have demonstrated varying degrees of efficacy in randomized trials and meta-analyses, but none of these interventions has robust enough evidence to be considered first-line therapy. These treatments may find a role in combination with guideline treatments or may be used in novel penile rehabilitation research protocols. With growing interest in alternative treatment for men's health, an awareness of the literature is imperative for patient counsel. Alternative treatments, like L-arginine, have a growing body of evidence for efficacy in combination with PDE5i, and low-intensity shock wave therapy and stem cell therapy continue to demonstrate encouraging outcomes in ED trials.

Evaluating the efficacy and safety of vascular IPL for treatment of acute cutaneous leishmaniasis: a randomized controlled trial.

Treatment of cutaneous leishmaniasis (CL) continues to be a health concern, and alternative therapies with fewer side effects are substantially needed. This study aimed to determine the efficacy of intense pulsed light (IPL) with wavelength spectrum affecting vascular lesions on acute cutaneous leishmaniasis. In this randomized clinical trial study, 30 patients with acute CL were enrolled. Baseline clinical and demographic data were recorded in the checklist after obtaining written informed consent. Patients were randomly allocated to receive either IPL fortnightly (intervention group) or intralesional meglumine antimoniate (MA) weekly (control group) over 10 weeks. Patients were assessed every 2 weeks to determine the size of induration and improvement rate of lesions. Follow-up visits were arranged at 3rd and 6th months. Overall, 15 patients (21 lesions) in the intervention group and 15 patients (22 lesions) in the control group were studied. The size of lesions in the control group was significantly higher at the baseline (P = 0.014) and the second week (P = 0.034), and significantly lower in the eighth week (P = 0.009), compared with the intervention group. The size of lesions in the control group changed during the study (P < 0.001), whereas changes were not significant in the intervention group. The trend of changes in size of lesions was faster in the control group (P < 0.001). More patients in the control group had higher improvement rate at the sixth (P = 0.005) and tenth (P < 0.001) weeks. At the end of study, the cure rate was 35% (7 out of 20 lesions) in intervention group and 81.8% (18 out of 22 lesions) in the control group. Complete response happened earlier in the control group (P < 0.001). None of the lesions that were cured before the tenth week relapsed after 6 months. The frequency of blistering was significantly higher in intervention group (P = 0.001). Our results indicated that IPL with wavelength spectrum affecting vascular lesions was inferior to intralesional MA in treatment of CL. However, it can be considered as a second-line option, especially in patients with limitations for use of MA. Trial registry:  https://www.irct.ir/trial/34246 IRCT20140414017271N5.

Phase II trial evaluating the clinical efficacy of cefixime for treatment of active syphilis in non-pregnant women in Brazil (CeBra).

BACKGROUND: Syphilis is a sexually and vertically transmitted infection caused by the bacteria Treponema pallidum for which there are few proven alternatives to penicillin for treatment. For pregnant women infected with syphilis, penicillin is the only WHO-recommended treatment that will treat the mother and cross the placenta to treat the unborn infant and prevent congenital syphilis. Recent shortages, national level stockouts as well as other barriers to penicillin use call for the urgent identification of alternative therapies to treat pregnant women infected with syphilis. METHODS: This prospective, randomized, non-comparative trial will enroll non-pregnant women aged 18 years and older with active syphilis, defined as a positive rapid treponemal and a positive non-treponemal RPR test with titer ≥1:16. Women will be a, domized in a 2:1 ratio to receive the oral third generation cephalosporin cefixime at a dose of 400 mg two times per day for 10 days (n = 140) or benzathine penicillin G 2.4 million units intramuscularly based on the stage of syphilis infection (n = 70). RPR titers will be collected at enrolment, and at three, six, and nine months following treatment. Participants experiencing a 4-fold (2 titer) decline by 6 months will be considered as having an adequate or curative treatment response. DISCUSSION: Demonstration of efficacy of cefixime in the treatment of active syphilis in this Phase 2 trial among non-pregnant women will inform a proposed randomized controlled trial to evaluate cefixime as an alternative treatment for pregnant women with active syphilis to evaluate prevention of congenital syphilis. TRIAL REGISTRATION: Trial identifier: www.Clinicaltrials.gov, NCT03752112. Registration Date: November 22, 2018.

When Drugs Do Not Work: Alternatives to Antiseizure Medications.

PURPOSE OF REVIEW: Despite the increase in the number of novel antiseizure medications over the past 20 years, approximately one-third of patients will not have adequate seizure control on medications. For these patients, additional options need to be considered, including dietary, device, and surgical treatments. In addition, many complementary therapies can be considered as adjunctive treatment, with the intent of improving quality of life for persons with epilepsy and potentially allowing for improvement in seizure control. RECENT FINDINGS: This review outlines established and developing treatments for drug-resistant epilepsy. Surgical treatments, including resective surgery and vagus nerve stimulation, have been routine care for several decades. In the last several years, new neurostimulation options have been approved (responsive neurostimulation and deep brain stimulation) or are under development (continuous subthreshold cortical stimulation). For patients with lesion or well-defined seizure-onset zones, less invasive options including laser ablation and ultrasound therapy provide the potential for faster recovery times and less morbidity. Not all therapies are in the pharmacological or surgical arenas. This review also explores the evidence for complementary treatments, including relaxation and meditation techniques, and art and music therapy. Despite the range of antiseizure medications available, they still provide inadequate for a large number of patients with epilepsy, either due to ongoing seizures or intolerable side effects. Complementary therapies, including diet, meditation techniques, and music therapy, provide compelling treatment options to improve quality of life while potentially improving seizure control. In appropriate patients, stimulation devices or surgical resection can offer options for significant seizure reduction or even cure. The full range of therapeutics should be considered for each patient with epilepsy when they are struggling with inadequate seizure control or side effects with traditional pharmacological treatment.

Candida Biofilms: An Update on Developmental Mechanisms and Therapeutic Challenges.

Fungi of the genus Candida are important etiological agents of superficial and life-threatening infections in individuals with a compromised immune system. One of the main characteristics of Candida is its ability to form highly drug tolerance biofilms in the human host. Biofilms are a dynamic community of multiple cell types whose formation over time is orchestrated by a network of transcription regulators. In this brief review, we provide an update of the processes involved in biofilm formation by Candida spp. (formation, treatment, and control), as well as the transcriptional circuitry that regulates its development and interactions with other microorganisms. Candida albicans is known to build mixed species biofilms with other Candida species and with various other bacterial species in different host niches. Taken together, these properties play a key role in Candida pathogenesis. In addition, this review gathers recent studies with new insights and perspectives for the treatment and control of Candida biofilms.

Topical Curcumin and Triamcinolone Acetonide in Recurrent Minor Aphthous Ulcers: A Pilot Trial.

AIM: To evaluate the efficacy of topical curcumin and topical triamcinolone acetonide in a professional population with minor aphthous ulcers by assessing six clinical variables: site, size, pain, healing period, frequency of recurrence and number of ulcers. MATERIALS AND METHODS: This randomized, parallel designed pilot trial was performed on 60 symptomatic individuals with minor aphthous ulcer. Willing participants were allocated randomly into group I and group II. Participants in group I were treated with topical curcumin and group II were treated with topical triamcinolone acetonide for a period of 6 months. All participants were blinded to the drug they received. Participants were assessed on day 1, day 3, day 5, day 7, and after healing for symptomatic reduction in pain, size, healing period, frequency of recurrence, and in the number of ulcers. Statistically, independent sample t test, Chi-square test, and Log rank Kaplan-Meier survival analysis were performed. RESULTS: Lower labial mucosa was found to be the predominant site of minor aphthous ulcer in both the groups. A gradual reduction in pain and size was noted in both the groups with statistical significance of p value <0.001. All the ulcers in both the groups healed completely without scarring within 2 weeks with statistical significance. In both the treatment groups, new ulcers occurred throughout the follow-up period of 6 months. The mean number of the ulcers are statistically not significant with p value >0.05. CONCLUSION: Our study showed clinically beneficial effects with topical curcumin with regard to ulcer size, pain, healing, and recurrence rate. Also topical curcumin gel was well tolerated and performed ot par with topical triamcinolone acetonide oral paste with a borderline favorable result with triamcinolone. CLINICAL RELEVANCE: Curcumin can be safely recommended on a long-term basis as a more appealing therapeutic agent and is a better alternative choice for aphthous ulcers in children, pregnant woman, lactating mother, and in immunocompromised individuals.

Combination of Clindamycin and Azithromycin as Alternative Treatment for Toxoplasma gondii Encephalitis.

Current standard therapies for toxoplasmic encephalitis often cause severe adverse events. A 57-year-old HIV-positive man in Japan who had toxoplasmic encephalitis but was intolerant to trimethoprim/sulfamethoxazole, pyrimethamine, sulfadiazine, and atovaquone was successfully treated with the combination of clindamycin and azithromycin. This drug combination can be an alternative treatment for this condition.

Celiac disease: a comprehensive current review.

BACKGROUND: Celiac disease remains a challenging condition because of a steady increase in knowledge tackling its pathophysiology, diagnosis, management, and possible therapeutic options. MAIN BODY: A major milestone in the history of celiac disease was the identification of tissue transglutaminase as the autoantigen, thereby confirming the autoimmune nature of this disorder. A genetic background (HLA-DQ2/DQ8 positivity and non-HLA genes) is a mandatory determinant of the development of the disease, which occurs with the contribution of environmental factors (e.g., viral infections and dysbiosis of gut microbiota). Its prevalence in the general population is of approximately 1%, with female predominance. The disease can occur at any age, with a variety of symptoms/manifestations. This multifaceted clinical presentation leads to several phenotypes, i.e., gastrointestinal, extraintestinal, subclinical, potential, seronegative, non-responsive, and refractory. Although small intestinal biopsy remains the diagnostic 'gold standard', highly sensitive and specific serological tests, such as tissue transglutaminase, endomysial and deamidated gliadin peptide antibodies, have become gradually more important in the diagnostic work-up of celiac disease. Currently, the only treatment for celiac disease is a life-long, strict gluten-free diet leading to improvement in quality of life, ameliorating symptoms, and preventing the occurrence of refractory celiac disease, ulcerative jejunoileitis, and small intestinal adenocarcinoma and lymphoma. CONCLUSIONS: The present review is timely and provides a thorough appraisal of various aspects characterizing celiac disease. Remaining challenges include obtaining a better understanding of still-unclear phenotypes such as slow-responsive, potential (minimal lesions) and seronegative celiac disease. The identification of alternative or complementary treatments to the gluten-free diet brings hope for patients unavoidably burdened by diet restrictions.

Dietary supplementation with caffeine increases survival rate, reduces microbial load and protects the liver against Aeromonas hydrophila-induced hepatic damage in the grass carp Ctenopharyngodon idella.

The indiscriminate use of antibiotics is a major concern for the aquaculture industry because of the increasing prevalence of bacterial resistance, including the emergence of multi-resistant strains of Aeromonas hydrophila. Therefore, alternative ecofriendly therapeutic or prophylactic approaches such as natural products have been suggested, including caffeine, a methylxanthine with potent bactericidal and antioxidant properties. The aims of this study were to evaluate whether dietary supplementation with caffeine exerted bactericidal effects against A. hydrophila, and to determine whether caffeine protected the liver of grass carp (Ctenopharyngodon idella) against A. hydrophila-induced oxidative damage. Experiment I evaluated the antimicrobial properties of caffeine dietary supplementation linked to longevity and mortality rates during aeromonosis. Fish infected with A. hydrophila that were fed diets containing 5% and 8% caffeine lived significantly longer than those fed with control diets. Experiment II evaluated hepatic oxidative stress-related parameters and microbial loads on day 7 post-infection. Levels of hepatic reactive oxygen species (ROS), lipid peroxidation (LOOH) and protein carbonylation (PC) levels were significantly higher in infected fish fed with control diet than in uninfected fish, and hepatic antioxidant capacity against peroxyl radicals (ACAP) levels, and superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione reductase (GR) activities were significantly inhibited. Dietary supplementation with 5% and 8% caffeine prevented the increase on hepatic ROS, LOOH and PC levels (except 5% caffeine) elicited by infection. Caffeine supplementation reduced or prevented the inhibition of hepatic SOD, GPx and GST activities. Finally, both caffeine concentrations reduced the hepatic microbial load compared to fish fed with control diets that were infected with A. hydrophila. Taken together, the data suggest that dietary supplementation with 8% caffeine may be considered a compelling prophylactic approach to aeromonosis caused by A. hydrophila.