Development and evaluation of sildenafil/glycyrrhizin-loaded nanofibers as a potential novel buccal delivery system for erectile dysfunction.

Erectile dysfunction (ED) is a growing health condition that needs safe and effective therapy. One of the main common treatments is sildenafil which is used in clinics for managing erectile dysfunction by enhancing the blood supply to the penis. In the current study, sildenafil was formulated as nanofibers and mixed with the root extract of Glycyrrhiza glabra (glycyrrhizin) as a natural sweetener to be administrated in the buccal cavity for enhanced drug bioavailability, rapid drug absorption and improved patient compliance. The formulated dual-loaded nanofibers were evaluated by measuring diameter, disintegration, drug loading efficiency, drug release profile, and in vitro cell viability assessment. The results showed that the sildenafil/glycyrrhizin-loaded fibers had a diameter of 0.719 ± 0.177 µm and lacked any beads and pores formation on their surfaces. The drug loading and encapsulation efficiency for sildenafil were measured as 52 ± 7 µg/mg and 67 ± 9 %, respectively, while they were 290 ± 32 µg/mg and 94 ± 10 %, respectively, for glycyrrhizin. The release rate of sildenafil and glycyrrhizin demonstrated a burst release in the first minute, followed by a gradual increment until a complete release after 120 min. The in vitro cell viability evaluation exhibited that the application of sildenafil and glycyrrhizin is safe upon 24-hour treatment on human skin fibroblast cells at all used concentrations (i.e., ≤ 1,000 and 4,000 µg/mL, respectively). However, the application of sildenafil-glycyrrhizin combination (in a ratio of 1:4) demonstrated more than 80 % cell viability at concentrations of ≤ 250 and 1000 µg/mL, respectively, following 24-hour cell exposure. Therefore, sildenafil/glycyrrhizin dual-loaded PVP nanofibers showed a potential buccal therapeutic approach for erectile dysfunction management.

Enhanced Biodegradation of Chlorpyrifos by Bacillus cereus CP6 and Klebsiella pneumoniae CP19 from municipal waste water.

Chlorpyrifos is one of the widely used pesticides induced genotoxicity, and neurotoxicity to mammals, fishes and other non-target organisms. In the current investigation pesticide degrading strains Bacillus cereus CP6 and Klebsiella pneumoniae CP19 were isolated from the municipal soil sediment sample and characterized based on biochemical, physiological, morphological characters and 16S rDNA sequencing. The strains B. cereus CP6 and K. pneumoniae CP19 survived and degraded more than 70% chlorpyrifos at 200-300 mg/L initial concentrations. K. pneumoniae CP19 was capable of degrading chlorpyrifos rapidly than B. cereus CP6 in submerged fermentation. Moreover, these two isolates have the ability to degrade pesticide in the presence of glucose as the carbon source and biodegradation potential was optimum at neutral pH. B. cereus CP6 utilized peptone and degraded pesticide, whereas, beef extract stimulated maximum degradation in the case of K. pneumoniae CP19. Moreover, bacterial consortium formulated using CP6 and CP19 strains degraded 93.4 ± 2.8% chlorpyrifos in liquid culture. The microbial consortium inoculated soil degraded 82.3 ± 1.3% within 14 days and maximum degradation (94.5 ± 3.3%) was achieved after 16 days. The findings revealed the potential of biocatalyst for the biodegradation of chlorpyrifos contaminated water.

Efficacy of ivermectin against colon cancer induced by dimethylhydrazine in male wistar rats.

Colon cancer (CC) is a common form of cancer worldwide. According to growing incidence of cancer and little information about the possible protective role of Ivermectin (IVM) on colon cancer, this study aimed to investigate the chemoprotective role of IVM against colon cancer induced by Dimethylhydrazine (DMH) in Male Wistar Rats. Based on LD50, three doses of IVM (0.25, 0.5, and 1 mg/kg) were applied before assayingthe antioxidant status, apoptotic markers, and microscopic analysis. Our result showed that glutathione (GSH) level was significantly increased in low dose of IVM-treated rats. Hight levels of oxidative stress and tissue damage consumed GSH and catalase (CAT), and dismutase (SOD) as indicated by significant drop in the treated groups. mRNA levels of Bax and caspase-3 were upregulated in rats treated with the high dose. Contrastingly, the expression of Bcl-2 was significantly downregulated with high dose. Changes in genes expression proved that IVM triggered apoptosis in treated groups compared to untreated control group. Microscopic analysis showed that rats treated with DMH exhibited high development of colorectal tumor. After induction of colorectal tumor, medium and high dose of DMH induced reduction in medullary carcinoma with great incidence of lymphoid nodules and desmoplastic reaction. In conclusion, this study demonstrates the potential of IVM as an anticancer drug against colon cancer in male Wistar rats.

COVID-19 vaccination for children in Malaysia - A position statement by the College of Paediatrics, Academy of Medicine of Malaysia.

The availability of COVID-19 vaccines and mass vaccination programmes in adults have significantly reduced the case attack rates and disease burden. COVID-19 vaccination successfully decreases the population at risk of infection, allowing for the safer re-opening of economies and reducing the pandemic's crippling impact on healthcare systems. However, the rapidly mutating severe acute respiratory syndrome-coronavirus-2 poses challenges in diminishing vaccine-induced immunity and vaccinating a significant proportion of adults to achieve herd immunity. These challenges necessitated adolescent vaccination. With the recent emergence of the highly transmissible Omicron variant and the increasing COVID-19 hospitalisation rates of children below 12 years old, many countries opted to also vaccinate younger children. Phase II/III clinical trials and real-world experience demonstrate that COVID-19 vaccinations are effective and safe for younger children and adolescents. Before Malaysia introduced its national COVID-19 vaccination programme for children 5-11 years old (which ran between March and June 2022), an expert advisory statement was issued by the College of Paediatrics, Academy of Medicine of Malaysia, to highlight the benefits and importance of vaccinating children. The advisory statement included clarifications about vaccine-related side effects such as post-vaccination myocarditis and allergic reactions to encourage informed decision making by healthcare providers and parents. This paper, which was prepared based on the critical appraisal of the current evidence, evaluation of the international experiences and the positive impact of COVID-19 vaccination in children, collectively sums up the rationale to support and ensure the success of the nationwide vaccination programme for children. Hence, the College recommends COVID-19 vaccination for children in Malaysia.

Inhibition of human amylin aggregation by Flavonoid Chrysin: An in-silico and in-vitro approach.

Islet amyloid polypeptide (amylin), consecrated by the pancreatic ß-cells with insulin, has a significant role to play in maintaining homeostasis of islet cell hormones. Alzheimer's disease is the predominant source of dementia. However, its etiology remains uncertain; it appears that type 2 diabetes mellitus and other prediabetic states of insulin resistance contribute to the intermittent Alzheimer's disease presence. Amylin is abnormally elevated in Type II diabetes patients, accumulated into amylin aggregates, and ultimately causes apoptosis of the ß-cells, and till date, its mechanism remains unclear. Several flavonoids have inhibitory effects on amylin amyloidosis, but its inhibition mechanisms are unknown. Screening a collection of traditional compounds revealed the flavone Chrysin, a potential lead compound. Chrysin inhibits amyloid aggregate formation according to Thioflavin T binding, turbidimetry assay. We report results of molecular interaction analysis of Chrysin with amylin which shows potent binding affinity against amylin. Pharmacokinetics and Drug likeness studies of Chrysin also suggest that it is a potential lead compound. Therefore, Chrysin prevented amylin aggregation.

Psychological symptoms among healthcare workers handling COVID-19 patients.

INTRODUCTION: Healthcare workers serve as the frontliners against the coronavirus 2019 disease (COVID-19) and this puts them most at risk of infection as they attend to numerous patients with unknown status. This study aimed to examine stress, anxiety, and depression among healthcare workers caring for COVID-19 patients in Sarawak General Hospital (SGH), Malaysia. MATERIALS AND METHODS: This cross-sectional observational study conducted in SGH during the pandemic with an online self-administered questionnaire composed of two parts, the socio-demographic characteristics, and the Depression Anxiety Stress Scale (DASS). RESULTS: A total of 105 healthcare workers responded to this study. A questionnaire in both Bahasa Melayu and English was used. The findings showed that all healthcare workers had mild anxiety, with the majority experiencing mild stress (57.1%), and almost half of the respondents experiencing mild depression (41%). Female subjects had a significant higher mean score in anxiety level and stress level compared to male subjects (10.0±3.20 vs. 8.6±2.93, p<0.05; 14.1±4.76 vs. 10.7±3.70, p<0.05, respectively). Staff who were transferred from other units to handle COVID-19 cases experienced more psychological symptoms. There were significant correlations between the depression, anxiety and stress levels among the healthcare workers and the number of children they had (r=0.739, p=0.001; r=0.642, p=0.001; r=1, p =0.001 respectively). However, the stress level among the healthcare workers was reversely correlated with their years of working experience (r=-0.199, p=0.042). CONCLUSION: This study identified some socio-demographic factors associated with increased levels of stress, anxiety and depression among the healthcare workers during pandemic, which may lay ground for future interventions.

CoAsy knockdown in TNBC cell lines resulted in no overt effect on cell proliferation in vitro.

Triple-negative breast cancer (TNBC) remains the most challenging breast cancer subtype to treat. CoA synthase (CoAsy) is a bifunctional enzyme, encoded by the COASY gene, which catalyzes the last two steps of CoA biosynthesis. COASY has been reported as a hit in several large RNAi library screens for cancer. Therefore, we sought to investigate the dependency of TNBC cell line proliferation on CoAsy expression. Initially, knockdown of CoAsy expression was achieved by RNAi and reduced proliferation was observed in two TNBC cell lines, HCC1806 and MDA-MB-231. To further investigate the role of CoAsy, we established stable inducible shRNA cell lines from the same TNBC cell lines as well as the normal-like breast cell line MCF10A. Three separate cell lines, each expressing one of three different shRNA constructs targeting COASY, and a non-targeted shRNA control cell line were generated from each parent cell line. The induction of COASY shRNA for 4 days resulted in >99% knockdown of CoAsy for all three COASY shRNA constructs. However, this robust knockdown of CoAsy protein expression had no detectable impact on cell growth with 4-day induction times. Even 8-day induction times resulted in no apparent impact on cell growth. There was also no effect of CoAsy knockdown on the rate of cell migration. Measurement of CoA levels in cell lysates indicated that CoAsy knockdown reduced CoA to approximately half the normal level. Thus, CoAsy knockdown showed no detectable effect on the in vitro proliferation and migration of these cell lines possibly due to the cell's ability to maintain adequate levels of CoA through some unknown mechanism.

Spinal subependymoma surgery: do no harm. Little may be more!

OBJECTIVE:  Outline the reported diagnostic and operative findings, and evaluate the surgical treatment outcome to clarify the best available recommendations. METHODS:  Ovid Medline, Embase and PubMed central databases were searched from inception until January 2019 using the terms (subependymoma and (spinal or cervical or thoracic)). The articles were reviewed for reported spinal subependymoma cases perioperative management and treatment outcomes. RESULTS:  A total of 49 papers provided data on 105 cases. 47 cases were reported in the last 5 years. The reported cases were two medullary-cervical, 35 cervical, 32 cervicothoracic, 21 thoracic, 12 thoracolumbar and three lumbar. Spinal subependymomas typically arise from within the central spinal canal, giving the appearance of an intramedullary mass, usually eccentric to one side. Symptoms at presentation ranged between 1 month to 17 years, (mean 3.5 years, median 2 years) and were over 3 years in 36, and over 8 years in 12 cases. Sensory symptoms are the most frequent 75(80%), followed by weakness in 60(64%), pain in 45(48%) and sphincter disturbance in 24(25%). Postoperative neurological function was reported in 78 cases, and worsening was reported in 40 cases (51%), of which, 29 (72%) had complete resection, 6 (15%) had subtotal resection and 5 (12%) had partial resection. Neurological status remained the same in 24 (30%) and improved in 14 (18%). CONCLUSION:  The reviewed cases report a rate of 65% total resection of which 57% had worsened function after surgery. There were no reports of malignant transformation; therefore, long-term survival is expected, and surgical caution should be exercised where there is minimal symptom progression.

A Longitudinal Analysis of Pressurized Wideband Absorbance Measures in Healthy Young Infants.

OBJECTIVES: Wideband absorbance (WBA) is an emerging technology to evaluate the conductive pathway (outer and middle ear) in young infants. While a wealth of research has been devoted to measuring WBA at ambient pressure, few studies have investigated the use of pressurized WBA with this population. The purpose of this study was to investigate the effect of age on WBA measured under pressurized conditions in healthy infants from 0 to 6 months of age. DESIGN: Forty-four full-term healthy neonates (17 males and 27 females) participated in a longitudinal study. The neonates were assessed at 1-month intervals from 0 to 6 months of age using high-frequency tympanometry, acoustic stapedial reflex, distortion product otoacoustic emissions, and pressurized WBA. The values of WBA at tympanometric peak pressure (TPP) and 0 daPa across the frequencies from 0.25 to 8 kHz were analyzed as a function of age. RESULTS: A linear mixed model analysis, applied to the data, revealed significantly different WBA patterns among the age groups. In general, WBA measured at TPP and 0 daPa decreased at low frequencies (<0.4 kHz) and increased at high frequencies (2 to 5and 8 kHz) with age. Specifically, WBA measured at TPP and 0 daPa in 3- to 6-month-olds was significantly different from that of 0- to 2-month-olds at low (0.25 to 0.31 kHz) and high (2 to 5 and 8 kHz) frequencies. However, there were no significant differences between WBA measured at TPP and 0 daPa for infants from 3 to 6 months of age. CONCLUSIONS: The present study provided clear evidence of maturation of the outer and middle ear system in healthy infants from birth to 6 months. Therefore, age-specific normative data of pressurized WBA are warranted.

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) origin and animal reservoir.

Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) is a novel coronavirus discovered in 2012 and is responsible for acute respiratory syndrome in humans. Though not confirmed yet, multiple surveillance and phylogenetic studies suggest a bat origin. The disease is heavily endemic in dromedary camel populations of East Africa and the Middle East. It is unclear as to when the virus was introduced to dromedary camels, but data from studies that investigated stored dromedary camel sera and geographical distribution of involved dromedary camel populations suggested that the virus was present in dromedary camels several decades ago. Though bats and alpacas can serve as potential reservoirs for MERS-CoV, dromedary camels seem to be the only animal host responsible for the spill over human infections.

Assessing the Impact of Smoking Cessation Interventions on Periodontal Health and Gingival Inflammation in Smokers with Periodontitis.

Background: Smoking is a well-established risk factor for periodontitis, a chronic inflammatory disease of the oral cavity. While smoking cessation has been linked to improved overall health, its specific impact on periodontal health and gingival inflammation in individuals with periodontitis remains less explored. Materials and Methods: We conducted a prospective cohort study involving 200 smokers diagnosed with periodontitis. Participants were divided into two groups: Group A received comprehensive smoking cessation interventions, including counseling and pharmacotherapy, while group B continued smoking without intervention. Periodontal health was assessed through clinical parameters, including probing depth (PD) and clinical attachment level (CAL), at baseline and 6 months post intervention. Gingival inflammation was evaluated using the Gingival Index (GI). Results: After 6 months, group A exhibited a significant reduction in mean PD (from 4.5 mm to 3.2 mm) and CAL (from 5.0 mm to 3.5 mm) compared to group B. Conversely, group B showed no significant change in these parameters. The GI score significantly decreased in group A (from 2.8 to 1.2) but remained unchanged in group B. Furthermore, group A demonstrated a higher rate of smoking cessation (72%) compared to group B (14%). Conclusion: Smoking cessation interventions play a crucial role in improving periodontal health and reducing gingival inflammation in smokers with periodontitis. The observed reductions in PD, CAL, and gingival inflammation highlight the potential benefits of smoking cessation on oral health outcomes in this high-risk population.

Surgical vs. Non-Surgical Management of Temporomandibular Joint Disorders: Clinical Outcomes.

Background: Temporomandibular joint disorders (TMDs) encompass a range of clinical conditions affecting the temporomandibular joint (TMJ) and associated structures. Management approaches for TMDs vary and include both surgical and non-surgical interventions. Materials and Methods: In this retrospective cohort study, medical records of 150 patients diagnosed with TMDs were reviewed. Patients were categorized into two groups: surgical intervention and non-surgical intervention. The surgical group underwent various surgical procedures, including arthroscopy, arthroplasty, and joint replacement, while the non-surgical group received conservative treatments such as physical therapy, pharmacotherapy, and occlusal splints. Pain levels, TMJ function, quality of life (QoL), and patient satisfaction were assessed at baseline and post-treatment (6 months and 1 year). Results: At the 6-month follow-up, both groups experienced a significant reduction in pain scores (surgical group: 6.3 ± 1.2 to 2.4 ± 0.9, non-surgical group: 6.1 ± 1.1 to 3.2 ± 1.0). TMJ function improved in both groups (surgical group: 2.5 ± 0.8 to 4.8 ± 0.6, non-surgical group: 2.6 ± 0.7 to 4.2 ± 0.9). QoL scores increased (surgical group: 35.2 ± 4.6 to 50.3 ± 5.1, non-surgical group: 35.5 ± 4.2 to 45.7 ± 4.8), and patient satisfaction rates were high (surgical group: 92%, non-surgical group: 87%) at the 1-year follow-up. Conclusion: Both surgical and non-surgical management approaches demonstrated significant improvements in pain relief, TMJ function, QoL, and patient satisfaction for individuals with TMDs.

Distribution of virulence genes in clinical isolates of hospital-associated and community-associated methicillin-susceptible Staphylococcus aureus from Terengganu, Malaysia.

Staphylococcus aureus is a common bacterial pathogen known to cause various kinds of infections due to its repertoire of virulence factors. This study aimed to investigate the distribution of 19 types of virulence genes among clinical isolates of methicillin-susceptible S. aureus (MSSA) using the polymerase chain reaction. A total of 109 MSSA isolates, i.e., 63 hospital-associated (HA) and 46 community-associated (CA) were collected from Hospital Sultanah Nur Zahirah, the main tertiary hospital in Terengganu, Malaysia, from July 2016 to June 2017. The most frequent virulence genes detected were hla (78.9%, n=86) and hld (78.0%, n=85) encoding hemolysins, lukED (56.9%, n=62) encoding leukotoxin ED, followed by seb (26.6%, n=29) and sea (24.8%, n=27) encoding enterotoxins. Among 34 (31.2%) isolates carrying six or more virulence genes, only five were multidrug resistant (MDR) while the remaining isolates were susceptible. Significant associations were discovered between the hld gene with CA-MSSA (p=0.016) and the seo gene with HA-MSSA (p=0.023). However, there is no significant association between virulence genes among the different types of infection. The clinical MSSA isolates in Terengganu showed high prevalence and high diversity of virulence gene carriage.

Prevalence and Predictive Factors of Rhabdomyolysis in COVID-19 Patients: A Cross-sectional Study.

Introduction: The aim of the present prospective observational study was to demonstrate the prevalence and predictive factors of rhabdomyolysis in coronavirus disease 2019 (COVID-19) patients. Methods: The study was performed on reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed COVID-19 patients admitted to the emergency department between March 2020 and March 2021. Peak creatinine phosphokinase (CPK) levels were used to define rhabdomyolysis. A CPK level equal to or more than 1000 IU/L was defined as the presence of moderate to severe rhabdomyolysis. We developed a COVID-19-related Rhabdomyolysis Prognostic rule (CORP rule) using the independent predictors of rhabdomyolysis in COVID-19 patients. Results: Five hundred and six confirmed COVID-19 patients (mean age 58.36 ± 17.83 years, 56.32% male) were studied. Rhabdomyolysis occurred in 44 (8.69%) cases throughout their hospitalization. Male gender (odds ratio [OR] = 2.78, 95% confidence interval [CI]: 1.28, 6.00), hyponatremia (OR = 2.46, 95% CI: 1.08, 5.59), myalgia (OR = 3.04, 95% CI: 1.41, 6.61), D-dimer >1000 (OR = 2.84, 95% CI: 1.27, 6.37), and elevated aspartate aminotransferase level (three times higher than normal range) (OR = 3.14, 95% CI: 1.52, 6.47) were the significant preliminary predictors of rhabdomyolysis. The area under the curve of the CORP rule was 0.75 (95% CI: 0.69, 0.81), indicating the fair performance of it in the prognosis of rhabdomyolysis following COVID-19 infection. The best cutoff of the CORP rule was 3, which had a sensitivity of 72.9% and a specificity of 72.7%. Conclusion: This prospective study showed that 8.69% of patients developed rhabdomyolysis following COVID-19 infection. The CORP rule with optimal cutoff can correctly classify 72.8% of COVID-19 patients at risk of developing rhabdomyolysis.

Ongoing decision-making dilemma for treatment of de novo spinal infections: a comparison of the Spinal Infection Treatment Evaluation Score with the Spinal Instability Spondylodiscitis Score and Spine Instability Neoplastic Score.

OBJECTIVE: De novo spinal infections are an increasing medical problem. The decision-making for surgical or nonsurgical treatment for de novo spinal infections is often a non-evidence-based process and commonly a case-by-case decision by single physicians. A scoring system based on the latest evidence might help improve the decision-making process compared with other purely radiology-based scoring systems or the judgment of a single senior physician. METHODS: Patients older than 18 years with an infection of the spine who underwent nonsurgical or surgical treatment between 2019 and 2021 were identified. Clinical data for neurological status, pain, and existing comorbidities were gathered and transferred to an anonymous spreadsheet. Patients without an MR image and a CT scan of the affected spine region were excluded from the investigation. A multidisciplinary expert panel used the Spine Instability Neoplastic Score (SINS), Spinal Instability Spondylodiscitis Score (SISS), and Spinal Infection Treatment Evaluation Score (SITE Score), previously developed by the authors' group, on every clinical case. Each physician of the expert panel gave an individual treatment recommendation for surgical or nonsurgical treatment for each patient. Treatment recommendations formed the expert panel opinion, which was used to calculate predictive validities for each score. RESULTS: A total of 263 patients with spinal infections were identified. After the exclusion of doubled patients, patients without de novo infections, or those without CT and MRI scans, 123 patients remained for the investigation. Overall, 70.70% of patients were treated surgically and 29.30% were treated nonoperatively. Intraclass correlation coefficients (ICCs) for the SITE Score, SINS, and SISS were 0.94 (95% CI 0.91-0.95, p < 0.01), 0.65 (95% CI 0.91-0.83, p < 0.01), and 0.80 (95% CI 0.91-0.89, p < 0.01). In comparison with the expert panel decision, the SITE Score reached a sensitivity of 96.97% and a specificity of 81.90% for all included patients. For potentially unstable and unstable lesions, the SISS and the SINS yielded sensitivities of 84.42% and 64.07%, respectively, and specificities of 31.16% and 56.52%, respectively. The SITE Score showed higher overall sensitivity with 97.53% and a higher specificity for patients with epidural abscesses (75.00%) compared with potentially unstable and unstable lesions for the SINS and the SISS. The SITE Score showed a significantly higher agreement for the definitive treatment decision regarding the expert panel decision, compared with the decision by a single physician for patients with spondylodiscitis, discitis, or spinal osteomyelitis. CONCLUSIONS: The SITE Score shows high sensitivity and specificity regarding the treatment recommendation by a multidisciplinary expert panel. The SITE Score shows higher predictive validity compared with radiology-based scoring systems or a single physician and demonstrates a high validity for patients with epidural abscesses.

When does too little pressure become too much? A case of spontaneous intracranial hypotension presenting with acute loss of consciousness.

Background: We present a unique case of spontaneous intracranial hypotension (SIH) presenting with acute collapse and loss of consciousness. Case Description: The affected patient suffered an abrupt decline in level of consciousness several weeks after initial diagnosis. The patient was urgently transferred to a specialist neurosurgical unit. Imaging showed bilateral subdural fluid collections with significant associated local mass effect. The treating team faced a clinical conundrum with a lack of clarity as to whether this sudden deterioration was secondary to the local pressure effect on brainstem traction from reduced intracranial pressure. A decision was made to proceed with urgent burr-hole decompression of the bilateral subdural fluid collections. Conclusion: After a protracted, complex postoperative course, the patient recovered to full functional independence. To the author's knowledge, this is the first case in literature describing successful surgical management of SIH, with bilateral burr-hole evacuation to relieve the paradoxical mass effect of bilateral subdural fluid collections.

A novel scoring system concept for de novo spinal infection treatment, the Spinal Infection Treatment Evaluation Score (SITE Score): a proof-of-concept study.

OBJECTIVE: De novo infections of the spine are an increasing healthcare problem. The decision for nonsurgical or surgical treatment is often made case by case on the basis of physician experience, specialty, or practice affiliation rather than evidence-based medicine. To create a more systematic foundation for surgical assessments of de novo spinal infections, the authors applied a formal validation process toward developing a spinal infection scoring system using principles gained from other spine severity scoring systems like the Spine Instability Neoplastic Score, Thoracolumbar Injury Classification and Severity Score, and AO Spine classification of thoracolumbar injuries. They utilized an expert panel and literature reviews to develop a severity scale called the "Spinal Infection Treatment Evaluation Score" (SITE Score). METHODS: The authors conducted an evidence-based process of combining literature reviews, extracting key elements from previous scoring systems, and obtaining iterative expert panel input while following a formal Delphi process. The resulting basic SITE scoring system was tested on selected de novo spinal infection cases and serially refined by an international multidisciplinary expert panel. Intra- and interobserver reliabilities were calculated using the intraclass correlation coefficient (ICC) and Fleiss' and Cohen's kappa, respectively. A receiver operating characteristic analysis was performed for cutoff value analysis. The predictive validity was assessed through cross-tabulation analysis. RESULTS: The conceptual SITE scoring system combines the key variables of neurological symptoms, infection location, radiological variables for instability and impingement of neural elements, pain, and patient comorbidities. Ten patients formed the first cohort of de novo spinal infections, which was used to validate the conceptual scoring system. A second cohort of 30 patients with de novo spinal infections, including the 10 patients from the first cohort, was utilized to validate the SITE Score. Mean scores of 6.73 ± 1.5 and 6.90 ± 3.61 were found in the first and second cohorts, respectively. The ICCs for the total score were 0.989 (95% CI 0.975-0.997, p < 0.01) in the first round of scoring system validation, 0.992 (95% CI 0.981-0.998, p < 0.01) in the second round, and 0.961 (95% CI 0.929-0.980, p < 0.01) in the third round. The mean intraobserver reliability was 0.851 ± 0.089 in the third validation round. The SITE Score yielded a sensitivity of 97.77% ± 3.87% and a specificity of 95.53% ± 3.87% in the last validation round for the panel treatment decision. CONCLUSIONS: The SITE scoring concept showed statistically meaningful reliability parameters. Hopefully, this effort will provide a foundation for a future evidence-based decision aid for treating de novo spinal infections. The SITE Score showed promising inter- and intraobserver reliability. It could serve as a helpful tool to guide physicians' therapeutic decisions in managing de novo spinal infections and help in comparison studies to better understand disease severity and outcomes.

Study of Some Resistance Genes in Clinical Proteus mirabilis.

Proteus mirabilis belongs to the family Enterobacteriaceae and is capable of transforming in shape from rod to elongated and swarming motility by flagella. It is an opportunity for bacteria and can cause different clinical diseases. Therefore, this study aimed to assay and detect a sequence of genes that encode for antibiotic resistance in multidrug resistance clinical isolates of Proteus mirabilis, including blaTEM, aac(6')-Ib, qnrA, IntI2, IntI1 and secondly to investigate the relationship in the phylogenetic tree among these genes in Iraq comparison with global strains in NCBI. The study included the identifying of 500 clinical samples depending on morphological and biochemical tests and confirming Proteus mirabilis diagnosis by the VITEK-2 Compact system. The confirmed isolates of Proteus mirabilis were 95 clinical isolates (19%). Antibiotic susceptibility test of all these isolates was done using twelve antibiotics tested using Amoxicillin, Aztreonam, Imipenem, Cefoxitin, Amikacin, Ceftazidem, Ciprofloxacin, Nalidixic acid, Gentamicin, Sulphamethazol-trimethoprim, Cefotaxime, Amoxicillin-clavulanic acid. The results showed that multidrug resistance Proteus mirabilis isolates contained the genes in different levels as follow blaTEM gene (90%), aac(6')-Ib gene (80%) ,IntI1 gene (100%), IntI2 gene (80%). These genes were sequenced and detected phylogenetic relationships among these genes and global genes were documented in NCBI. The results showed that some Iraqi isolates contain genetic variation compared to global strains. Therefore, this variation was detected and registered in NCBI of all five antibiotic resistance genes mentioned above and accepted under accession numbers of aacIb gene (LC613168.1), blaTEM gene (LC613166.1), IntI1 gene (LC613169.1), IntI2 gene (LC613170.1).

Optimization of subcritical water pre-treatment for biogas enhancement on co-digestion of pineapple waste and cow dung using the response surface methodology.

The optimal pre-treatment method and conditions depend on the types of lignocellulose present due to the complexity and the variability of biomass chemical structures. This study optimized subcritical water pre-treatment to ensure maximum methane production from pineapple waste prior to anaerobic co-digestion with cow dung using the response surface methodology. A central composite design was achieved with three different factors and one response. A total of 20 pre-treatment runs were performed at different temperatures, reaction times and water to solid ratios suggesting optimum values for subcritical water pre-treatment at 128.52℃ for 5 min with 5.67 to 1 water to solid ratio. Under these conditions, methane yield increased from 59.09 to 85.05 mL CH4/g VS with an increase of 23% biogas yield and 44% methane yield from the untreated. All pre-treatments above 200℃ showed reductions in biogas yield. Compositional analysis showed slight reduction of lignin and increase in α-cellulose content after the pre-treatment. Analysis using Fourier transform infrared spectroscopy and thermogravimetric analysis verified the presence of cellulosic material in pre-treated pineapple waste. Most of the hemicellulose was solubilized in the liquid samples after SCW pre-treatment. The crystallinity index of pineapple waste was reduced from 57.58% (untreated) to 54.29% (pre-treated). Scanning electron microscopy confirmed the structural modification of pre-treated pineapple waste for better microbial attack. Subcritical water pre-treatment is feasible as a promising method to enhance the anaerobic co-digestion process. Further study should be conducted to assess the scale-up of the process from pre-treatment to anaerobic digestion at the pilot plant level.

A possible theranostic approach of chitosan-coated iron oxide nanoparticles against human colorectal carcinoma (HCT-116) cell line.

Iron oxides have become increasingly popular for their use as a diagnostic and therapeutic tool in oncology. This study aimed to improve pharmacological valuable of Fe3O4, which may be use to diagnosis colorectal cancers (CRC). Here, we have developed chitosan (CS) coated Fe3O4 through a cost-effective procedure. First, we determined the characterization of OA-C-Fe3O4 by FTIR, UV-Vis spectra, and TEM. Then, we evaluated the photodynamic therapeutic (PDT) activity of OA-C-Fe3O4 in human colorectal carcinoma cell lines (HCT 116). Current results revealed that the light-induced enhanced reactive oxygen species (ROS) activity of the nanoparticles (NPs) and caused cell death via the activity of caspase 9/3. The in vitro magnetic resonance imaging (MRI) experiments in (HCT 116) and human embryonic kidney cells (HEK 293) illustrated that nanohybrid is an effective MRI contrasting agents for the diagnosis of colorectal cancer.