An animal study on the effectiveness of platelet-rich plasma as a direct pulp capping agent.

Direct pulp capping (DPC) is a conservative approach for preserving tooth vitality without requiring more invasive procedures by enhancing pulp healing and mineralized tissue barrier formation. We investigated the effectiveness of Platelet Rich Plasma (PRP) vs. Mineral Trioxide Aggregate (MTA) as a DPC agent. Forty-two teeth from three mongrel dogs were divided into two equal groups. After three months, the animals were sacrificed to evaluate teeth radiographically using cone-beam computerized tomography, histopathologically, and real-time PCR for dentin sialophosphoprotein (DSPP), matrix extracellular phosphoglycoprotein (MEPE), and nestin (NES) mRNA expression. Radiographically, hard tissue formation was evident in both groups without significant differences (p = 0.440). Histopathologic findings confirmed the dentin bridge formation in both groups; however, such mineralized tissues were homogenous without cellular inclusions in the PRP group, while was osteodentin type in the MTA group. There was no significant difference in dentin bridge thickness between the PRP-capped and MTA-capped teeth (p = 0.732). The PRP group had significantly higher DSPP, MEPE, and NES mRNA gene expression than the MTA group (p < 0.05). In conclusion, PRP enables mineralized tissue formation following DPC similar to MTA, and could generate better cellular dentinogenic responses and restore dentin with homogenous architecture than MTA, making PRP a promising alternative DPC agent.

Worst pattern of invasion and other histopathological features in oral cancer as determinants of prognosis and survival rate: A retrospective cohort analysis.

Oral cavity squamous cell carcinoma (OCSCC) is a well-recognized malignancy of the head and neck. Studies on patients with early-stage oral cancer have shown that they develop locally recurring and/or regional lymph node metastasis, which results in disease-associated mortality. Thus, early-stage oral cancer does not always present good prognoses. The present study aimed to determine the efficacy of using worst pattern of invasion (WPOI) and other histopathological features, such as prognostic factors in OCSCC, and analyze the impact of resection margin status and histopathological prognostic indicators on local recurrence (LR) and overall survival (OS) in patients with OCSCC. A retrospective cohort study was conducted by reviewing the charts of 63 patients with OCSCC treated with primary surgery at King Abdulaziz University Hospital between 2012 and 2019. An author and an experienced pathologist reviewed pathology slides. Associations of histopathological factors, including differentiation, stage, lymphovascular invasion, extracapsular extension, perineural invasion (PNI), WPOI and surgical margins, with LR or disease-free survival (DFS) were evaluated. Univariate analysis identified WPOI and PNI, and multivariate analysis identified the WPOI as predictive factors for LR and DFS. Kaplan-Meier analysis identified the WPOI and PNI as predictive factors for OS and WPOI as a predictive factor for DFS. Therefore, it may be concluded that WPOI and PNI are significant independent prognostic factors for local tumor control and DFS in patients with OCSCC.

Awareness on Teratogenic Effects of Isotretinoin and Compliance with Precautionary Measures among Women of Childbearing Age in Makkah Province, Saudi Arabia.

Acne vulgaris ranks among the most common dermatologic conditions encountered during adolescence up to adulthood. For moderate to severe cases of acne, isotretinoin is indicated as it is considered the most efficacious medication against acne. However, isotretinoin use is known to have its side effects and most importantly is the drug's teratogenic potential. As a response, programs such as the Retinoid Pregnancy Prevention Program (PPP), System to Manage Accutane-Related Teratogenicity (SMART), and iPLEDGE were put into action as attempts to promote awareness on isotretinoin's teratogenicity and reduce the incidence of exposed pregnancies. Such programs are lacking in Saudi Arabia. This study aimed, therefore, to evaluate the awareness of women of childbearing age in Makkah Province, Saudi Arabia, with regards to the side effects of the medication, specifically its teratogenicity. This study also intended to assess the compliance of both doctors and patients with the recommendations and precautions associated with isotretinoin. A cross-sectional study was conducted on 766 women participants using a previously validated questionnaire. Results showed that majority of the respondents (91%) are generally aware of the side effects of isotretinoin use, particularly its teratogenicity. However, lapses have been identified with regards to the compliance of both the treating physician and the patient. Three-fourths of sexually active women did not use any form of contraception while being on isotretinoin treatment. Two-thirds of the study participants responded that they were not issued approval forms indicating their understanding of the side effects of isotretinoin and the importance of compliance to the treating physician's instructions; 11.5% claimed that their doctors did not perform any blood tests; and 67.7% claimed that no pregnancy test was performed at any time during the treatment. These findings strongly suggest a need for improvement when it comes to compliance of both doctors and patients. It is recommended that doctor-patient communication be more comprehensive and more efforts should be made to follow international guidelines in that regard.

New Approaches for the Synthesis of Heterocyclic Compounds Corporating Benzo[d]imidazole as Anticancer Agents, Tyrosine, Pim-1 Kinases Inhibitions and their PAINS Evaluations.

BACKGROUND: Benzo[d]imidazoles are highly biologically active, in addition, they are considered as a class of heterocyclic compounds with many pharmaceutical applications. OBJECTIVE: We are aiming in this work to synthesize target molecules that possess not only anti-tumor activities but also kinase inhibitors. The target molecules were obtained starting from the benzo[d]imidazole derivatives followed by their heterocyclization reactions to produce anticancer target molecules. METHODS: The 1-(1H-benzo[d]imidazol-2-yl)propan-2-one (3) and the ethyl 2-(1H-benzo[d]imidazol-2- yl)acetate (16) were used as the key starting material which reacted with salicylaldehyde to give the corresponding benzo[4,5]imidazo[1,2-a]quinoline derivatives. On the other hand, both of them were reacted with different reagents to give thiophene, pyran and benzo[4,5]imidazo[1,2-c]pyrimidine derivatives. The synthesized compounds were evaluated against the six cancer cell lines A549, HT-29, MKN-45, U87MG, SMMC-7721, and H460 together with inhibitions toward tyrosine kinases, c-Met kinase and prostate cancer cell line PC-3 using the standard MTT assay in vitro, with foretinib as the positive control. RESULTS: Most of the synthesized compounds exhibited high inhibitions toward the tested cancer cell lines. In addition, tyrosine and Pim-1 kinases inhibitions were performed for the most active compounds where the variation of substituent through the aryl ring and heterocyclic ring afforded compounds with high activities. Our analysis showed that there is a strong correlation between the structure of the compound and the substituents of target molecules. CONCLUSION: Our present research proved that the synthesized heterocyclic compounds with varieties of substituents have a strong impact on the activity of compounds. The evaluations through different cell lines and tyrosine kinases indicated that the compounds were the excellent candidates as anticancer agents. This could encourage doing further research within this field for the building of compounds with high inhibitions.

New Approaches for the Synthesis of Fused Thiophene, Pyrazole, Pyran and Pyridine Derivatives with Anti-Proliferative Together with c-Met Kinase and Prostate Cancer Cell Inhibitions.

BACKGROUND: Recently multi-component reactions producing pyran and pyridine derivatives acquired a special attention due to their wide range of pharmacological activities, especially therapeutic activities. Through the market, it was found that many pharmacological drugs containing the pyran and pyridine nucleus were known. OBJECTIVE: We are aiming in this work to synthesize target molecules possess not only anti-tumor activities but also kinase inhibitors. The target molecules were obtained starting from cyclohexane-1,3-dione followed by its heterocyclization reactions to produce anticancer target molecules. METHODS: This work demonstrated multi-component reactions of cyclohexan-1,3-dione with aromatic aldehydes and diethylmalonate using triethylamine as a catalyst to give the 7,8-dihydro-4H-chromen-5(6H)-one derivatives 4a-c. The reaction of compounds 4a-c with either of hydrazine hydrate of phenylhydrazine gave the chromeno[2,3-c]pyrazole derivatives 5a-f, respectively. In addition, further heterocyclization reactions were adopted to give the chromeno[3,2-d]isoxazole, chromene-3-carboxamide derivatives. Moreover, the multicomponent reaction of cyclohexan-1,3-dione (1) with either of aromatic aldehydes and diethylmalonate using a catalytic amount of ammonium acetate gave the 1,4,5,6,7,8-hexahydroquinoline derivatives 13a-c. The antiproliferative activities of the synthesized compounds toward the six cancer cell lines namely A549, H460, HT- 29, MKN-45, U87MG, and SMMC-7721 were studied. In addition, the c-Met enzymatic activities and inhibition toward the prostate cancer cell PC-3 were measured. RESULTS: Anti-proliferative evaluations, c-Met enzymatic activities and inhibition toward the prostate cancer cell PC-3 were measured, and the results obtained in most cases indicated that the presence of electronegative Cl group through the molecule favour the inhibitions. CONCLUSION: The compounds with high anti-proliferative activity towards the cancer cell lines were 4a, 4b, 6d, 6e, 6f, 10e, 10f, 12c, 14e, 14f, 15c, 16d, 16e, 16f, 19c and 20c. Compounds 4b, 6c, 6d, 8b, 10c, 10d, 12b, 13b, 14c, 14d, 15b, 16c, 16d, 17b, 17c, 19b, 20b and 20c exhibited high potency against c-Met kinase and compounds 4a, 4b, 6b, 6c, 6d, 6f, 8b, 8c, 10c, 10d, 10e, 12b, 12c, 13a, 13b, 13c, 14c, 14d, 14e, 14f, 15b, 15c, 16b, 16c, 16d, 17b, 17c, 19c, 19d, 20a, 20b and 20c displayed high inhibitions toward PC-3 cell line.

An assessment of HIV patient's adherence to treatment and need for pharmaceutical care in Jordan.

OBJECTIVE: The objective of the present study was to explore the barriers and supporting factors for adherence among HIV patients and to explore their needs for pharmaceutical care services. METHODS: This study utilizes in-depth interviews with HIV patients. Out of 50 patients approached, a total of 30 patients agreed to participate in the study. The researchers used a predesigned topic guide. The interview guide included two parts; the first one focused on the assessment of HIV patients' adherence to their treatment. The second part focused on patients' need for pharmaceutical care services. RESULTS: Three main themes emerged from the interviews. Those included patient-related factors, medication-related factors and Healthcare professional related factors. This study found that a number of barriers that decreased adherence in HIV patients included stigmatisation, fear from disclosure, dosage form of the drug, adverse events and poor cooperation from healthcare professionals. On the other side supporting factors included family and friends support, electronic mobile reminders, feeling responsible to raising children, religious beliefs and feeling improvement while using therapy. Furthermore, the study illustrated that HIV patients need to have a specialist pharmacist in their healthcare team who delivers specialised pharmaceutical care services which may increase patients' adherence. CONCLUSIONS: The current study reveals a margin for medication adherence improvement in HIV patients. Patients in this study demonstrated the need for a pharmaceutical care. Future disease management and clinical pharmacy services programs should address the current study findings in order to improve the health service for HIV patients.

Diabetic foot infection caused by Raoultella ornithinolytica.

PURPOSE: The case of a diabetic foot infection caused by Raoultella ornithinolytica is reported. SUMMARY: A 68-year-old Caucasian man arrived at the hospital with a fever (38.5 °C) and a foul-smelling pressure ulcer on his left foot and was admitted for treatment of a moderate diabetic foot infection. The patient's medical history included type II diabetes mellitus, hypertension, chronic kidney disease, dyslipidemia, cataract surgery, and total hip arthroplasty. A tissue biopsy of the diabetic foot lesion was performed, and a blood sample was cultured. Empirical antimicrobial treatment consisting of amoxicillin-clavulanate 1.2 g (of amoxicillin) i.v. every 12 hours and ciprofloxacin 200 mg i.v. every 12 hours was initiated to target aerobic gram-positive and gram-negative and anaerobic microorganisms. After 48 hours, the results of the blood culture were negative, but the left ankle wound culture grew R. ornithinolytica. Although the isolated R. ornithinolytica was relatively sensitive, showing resistance only to cefazolin and ampicillin, the antibiotic regimen was not changed. The patient showed clinical and laboratory improvement during his 5-day hospitalization. Subsequently, i.v. antibiotics were discontinued, and the patient was discharged on oral amoxicillin-clavulanate 1 g (of amoxicillin) twice daily and oral ciprofloxacin 750 mg twice daily for an additional 9 days to complete a total duration of 14 days of treatment, after which the infection was completely resolved. CONCLUSION: A 68-year-old man diagnosed with a diabetic foot infection caused by R. ornithinolytica was successfully treated with amoxicillin-clavulanate and ciprofloxacin.

Genetic variability analysis of Zymomonas mobilis strains from the UFPEDA microorganisms collection.

Zymomonas mobilis is a Gram-negative bacterium that has drawn attention in the bioethanol industry. Besides bioethanol, this bacterium also produces other biotechnological products such as levans, which show antitumor activity. Molecular studies involving Z. mobilis have advanced to the point that allows us to characterize interspecies genetic diversity and understand their metabolism, and these data are essential for better utilization of this species. In this study, the genetic diversity of 24 strains from the Microorganisms Collection of Departamento de Antibióticos (UFPEDA) from Universidade Federal de Pernambuco were characterized. The methods used were amplified ribosomal DNA restriction analysis and diversity analysis of the internally transcribed 16S-23S rDNA spacer region (ISR). These analyses revealed low genetic variability of the 16S rDNA gene. These data confirm that these isolates are, or are closely related to, Z. mobilis. Moreover, the analysis of the ISR confirmed the genetic variability of strains deposited in the UFPEDA collection of microorganisms and grouped these strains into ten ribotypes, which can be used in the future for breeding programs and for the preservation of biodiversity. Furthermore, this study characterized the genetic variability between the UFPEDA 205/ ZAP, UFPEDA 98/AG11, and ZAG strains, which were obtained by spheroplast fusion among them. The data also indicate that there is genetic variability among the UFPEDA 202/CP4 and UFPEDA 633/ ZM4 strains, demonstrating that these important Z. mobilis strains are distinct, as suggested in previous studies.

Predictive value of prior colonization and antibiotic use for third-generation cephalosporin-resistant enterobacteriaceae bacteremia in patients with sepsis.

BACKGROUND: To prevent inappropriate empiric antibiotic treatment in patients with bacteremia caused by third-generation cephalosporin (3GC)-resistant Enterobacteriaceae (3GC-R EB), Dutch guidelines recommend ß-lactam and aminoglycoside combination therapy or carbapenem monotherapy in patients with prior 3GC-R EB colonization and/or recent cephalosporin or fluoroquinolone usage. Positive predictive values (PPVs) of these determinants are unknown. METHODS: We retrospectively studied patients with a clinical infection in whom blood cultures were obtained and empiric therapy with broad-spectrum ß-lactams and/or aminoglycosides and/or fluoroquinolones was started. We determined the PPVs of prior colonization and antibiotic use for 3GC-R EB bacteremia, and the consequences of guideline adherence on appropriateness of empiric treatment. RESULTS: Of 9422 episodes, 773 (8.2%) were EB bacteremias and 64 (0.7%) were caused by 3GC-R EB. For bacteremia caused by 3GC-R EB, PPVs of prior colonization with 3GC-R EB (90-day window) and prior usage of cephalosporins or fluoroquinolones (30-day window) were 7.4% and 1.3%, respectively, and PPV was 1.8% for the presence of any of these predictors. Adherence to Dutch sepsis guideline recommendations was 27%. Of bacteremia episodes caused by 3GC-R and 3GC-sensitive EB, 56% and 94%, respectively, were initially treated with appropriate antibiotics. Full adherence to guideline recommendations would hardly augment proportions of appropriate therapy, but could considerably increase carbapenem use. CONCLUSIONS: In patients receiving empiric treatment for sepsis, prior colonization with 3GC-R EB and prior antibiotic use have low PPV for infections caused by 3GC-R EB. Strict guideline adherence would unnecessarily stimulate broad-spectrum antibiotic use.

Estudo da procedência dos pacientes e dos tipos de tireoidopatias encontradas no ambulatório de endocrinologia do HSL-PUCRS nos anos de 2005 e 2006 / Study of the origin of patients and types of thyroidopathies observed in the endocrinology outpatient Department of Hospital São Lucas - PUCCRS from 2005-2006

Objetivos: Identificar a procedência e as características clínicas dos pacientes em acompanhamento no ambulatório de tireoidopatias do HSL-PUCRS entre 2005-2006. Métodos: Realizazado estudo retrospectivo, sendo que do total de 824 consultas agendadas no período de 1º de julho de 2005 a 31 de julho de 2006 foram revisados aleatoriamente os peontuários de 432 pacientes. Destes, 185 apresentaram as patologias em estudo, sendo seus dados protocolados. Os resultados foram analisados através de estatística descritiva, teste do qui-quadrado e exato de fisher. Resultados: a distribuição das doenças em estudo segundo ordem de frequência foram: tireoidite de Hashimoto (51,9% dos casos), doença de Graves (35,1%), bócio multinodular tóxico (9,7%) e adenoma tóxico (3,2%). Foram procedentes de Porto Alegre 37,3% dos pacientes e 61,1% eram de outros locais. Houve diferença estatísticamente significativa (p<0,005) quanto à presença de auto-anticorpos entre as doenças mediadas pela auto-imunidade e aquelas em que não há envolvimento da mesma. Os pacientes com tireoidite de Hashimoto realizaram reposição de hormônios em 94,8% do casos e os portadores de doença de Graves realizaram terapia medicamentosa anteriormente ao iodo radioativo em 37 casos ( 56,9). Conclusões: Os pacientes eram procedentes, em sua grande maioria, de locais próximos à região metropolitana. Acredita-se que seja menos oneroso o deslocamento do paciente e centros de atendimento de nível terciário do que a implementação de um serviço altamente especializado nessas regiões.

[Helicobacter pylori identification by brush gastric cytology: a comparison with histologic method]. / Identificação do Helicobacter pylori pela citologia do escovado gástrico: comparação com o método histológico.

The purpose of this study was to verify the efficacy of brush gastric cytology for diagnosis of Helicobacter pylori infection in patients, submitted to elective gastroscopy, compared to the method of endoscopic histology. Endoscopy was performed on 157 patients, divided into two dyspeptic groups: group A (n = 27) with duodenal ulcer; and group B (n = 130) without ulcer. In group A, the percentage of positive cases detected by brush cytology (77.8%) was similar to histology (74.1%; p = 0.3). While in group B, brush cytology (71.5%) was superior to histology (63.1%; p = 0.00002). Brush cytology is a simple and useful diagnostic method. It was efficient for identification of Helicobacter pylori infection in both groups.

Identificação do Helicobacter pylori pela citologia do escovado gástrico: comparação com o método histológico / Helicobacter pylori identification by brush gastric cytology: a comparison with histologic method

A proposta deste estudo foi a de verificar o valor da citologia do escovado gástrico no diagnóstico da infecção pelo Helicobacter pylori em pacientes submetidos à endoscopia digestiva, comparando-o a outro método endoscópico - a histologia. As endoscopias foram realizadas em 157 pacientes dispépticos, divididos em dois grupos: grupo A (n = 27) com úlcera duodenal, B (n = 130), sem úlcera. No grupo A, a porcentagem de pacientes positivos na citologia (77,8 por cento) foi similar à histologia (74,1 por cento; p = 0,3). No grupo B, a citologia (71,5 por cento) foi superior à histologia (63,1 por cento; p = 0,00002). A citologia do escovado gástrico é um método simples e prático. Foi eficiente para identificar a infecção pelo Helicobacter pylori em todos grupos de estudo.