Decoding the secrets of small extracellular vesicle communications: exploring the inhibition of vesicle-associated pathways and interception strategies for cancer treatment.

Cancer disease is the second leading cause of death worldwide. In 2023, about 2 million new cancer cases and 609,820 cancer deaths are projected to occur in the United States. The driving forces of cancer progression and metastasis are widely varied and comprise multifactorial events. Although there is significant success in treating cancer, patients still present with tumors at advanced stages. Therefore, the discovery of novel oncologic pathways has been widely developed. Tumor cells communicate with each other through small extracellular vesicles (sEVs), which contribute to tumor-stromal interaction and promote tumor growth and metastasis. sEV-specific inhibitors are being investigated as a next-generation cancer therapy. A literature search was conducted to discuss different options for targeting sEV pathways in cancer cells. However, there are some challenges that need to be addressed in targeting sEVs: i) specificity and toxicity of sEV inhibitor, ii) targeted delivery of sEV inhibitors, iii) combination of sEV inhibitors with current standard chemotherapy to improve patients' clinical outcomes, and iv) data reproducibility and applicability at distinct levels of the disease. Despite these challenges, sEV inhibitors have immense potential for effectively treating cancer patients.

Deciphering the interactions of scopoletin and scopolin from Catunaregam nilotica roots against Naja nigricollis phospholipase A2 enzyme.

Catuneragam nilotica has been used in ethnomedicine to treat snakebite, inflammation, and diarrhea among others. The aim of this research is to isolate, and characterize potential potential phospholipase A2 (PLA2) inhibitors from the roots of C. nilotica. The plant material was collected, authenticated, and sequentially extracted using solvents of increasing polarity starting from n-hexane, ethyl acetate, and methanol. The extracts as reported in our previous work, were screened in vitro for their inhibitory activity against PLA2 enzyme from N. nigricollis venom using acidimetric assay. In line with the bio-activity guided isolation, methanol extract (being the most active) was subjected to chromatographic separation using silica gel and sephadex LH-20 which resulted in the isolation and characterization of scopoletin, and scopolin; the compounds were able to inhibit the hydrolytic actions of PLA2 enzyme with percentage inhibition ranging from 67.82 to 100.00 % and 65.76-93.15 %, respectively while the standard Antisnake Venom (ASV) had 74.96-85.04 % after 10 min incubation at 37 °C. The molecular docking of the compounds against PLA2 enzyme was performed using Auto Dock Vina while ADME-Tox analysis was evaluated using swissADME and ProTox-II online servers; The findings indicated that both compounds were able to bind to the active site of PLA2 enzyme with high affinity (-6.5 to -6.2 kcal/mol) and they exhibited favorable drug-likeness and pharmacokinetic properties, and according to toxicity predictions, scopolin was found to be non-toxic (LD50 of 5000 mg/kg) while scopoletin has a slight chance of being toxic (LD50 of 3800 mg/kg). In conclusion, the findings of the research revealed that the roots of C. nilotica contains phytoconstituents with anti-PLA2 enzyme activity and thus, validates the ethnomedicinal claim of the use of the plant as herbal therapy against N. nigricollis envenomation.

Clinical Comparison of Three Indirect Pulp Capping Restorative Protocols: A Randomized Controlled Prospective Study.

OBJECTIVES: The objective of this prospective double-blind clinical trial was to compare clinical outcomes of indirect pulp capping restorative protocols on permanent teeth over a 12-month period. METHODS AND MATERIALS: Deep carious lesions in permanent teeth (90) were randomly assigned to three indirect pulp capping protocols (n=30: TheraCal LC, Dycal, and no liner). All teeth were restored with resin composite. The outcome measures were pain (VAS scale) and success rate (pulp vitality based on percussion, palpation, cold test, and radiographic findings), collected at screening, intervention, and 24-hour, 7-day, 3-month, 6-month, and 12-month follow-up visits. RESULTS: There was no statistically significant difference in tooth sensitivity among the three indirect pulp capping protocols nor in success rates among the restorative protocols after 1 year of follow-up (p>0.1).The respective success rates, as defined by the tooth remaining vital, after 1 year were: 96.2% for TheraCal LC, 100% for Dycal, and 100% for no liner. CONCLUSIONS: After 12-month evaluation, the success rate of indirect pulp capping therapy on permanent teeth was not affected by the pulp capping restorative protocol.

First molecular detection of porcine circovirus type 4 (PCV4) in Malaysia.

Porcine circovirus type 4 (PCV4) is the newest member in the porcine circovirus family, first reported in 2020. To date, the presence of PCV4 has only been reported in China, South Korea and most recently in Thailand. Detection of PCV4 have been reported in various production stages of pigs from piglets, finishers to sows; associated with a myriad of clinical manifestations including porcine dermatitis and nephropathy syndrome (PDNS), postweaning multisystemic wasting syndrome (PMWS), respiratory, enteric and neurological diseases. While successful virus isolation and culture has yet to be reported, pathogenicity of PCV4 has been demonstrated through infectious clone studies. The objective of this study is to investigate the presence of PCV4 in Malaysian porcine population to update the epidemiology of porcine circoviruses in Malaysia. A total of 49 samples from commercial intensive pig farms, abattoir and wild boar population were subjected to conventional polymerase chain reaction assay to detect PCV4 capsid (cap) genome. Resulting cap nucleotide sequences were analyzed for maximum likelihood phylogeny relationship. Results revealed that PCV4 is present in Peninsular Malaysia at a molecular prevalence of 4.08% (2 / 49 samples). Both PCV4 positive samples originated from clinically healthy finishers. Malaysian PCV4 strains were classified as genotype PCV4b, and were found to be phylogenetically distinct from the China, South Korea and Thailand strains. With this latest update of the novel PCV4 in Malaysia, it is clear that more attention needs to be given to the investigation of novel porcine circoviruses (PCV) and management of PCV diseases.

First molecular detection of porcine circovirus type 4 (PCV4) in Malaysia

@#Porcine circovirus type 4 (PCV4) is the newest member in the porcine circovirus family, first reported in 2020. To date, the presence of PCV4 has only been reported in China, South Korea and most recently in Thailand. Detection of PCV4 have been reported in various production stages of pigs from piglets, finishers to sows; associated with a myriad of clinical manifestations including porcine dermatitis and nephropathy syndrome (PDNS), postweaning multisystemic wasting syndrome (PMWS), respiratory, enteric and neurological diseases. While successful virus isolation and culture has yet to be reported, pathogenicity of PCV4 has been demonstrated through infectious clone studies. The objective of this study is to investigate the presence of PCV4 in Malaysian porcine population to update the epidemiology of porcine circoviruses in Malaysia. A total of 49 samples from commercial intensive pig farms, abattoir and wild boar population were subjected to conventional polymerase chain reaction assay to detect PCV4 capsid (cap) genome. Resulting cap nucleotide sequences were analyzed for maximum likelihood phylogeny relationship. Results revealed that PCV4 is present in Peninsular Malaysia at a molecular prevalence of 4.08% (2 / 49 samples). Both PCV4 positive samples originated from clinically healthy finishers. Malaysian PCV4 strains were classified as genotype PCV4b, and were found to be phylogenetically distinct from the China, South Korea and Thailand strains. With this latest update of the novel PCV4 in Malaysia, it is clear that more attention needs to be given to the investigation of novel porcine circoviruses (PCV) and management of PCV diseases.

Perineal hernia mesh repair: a fixation with glue, sutures and tacks. How to do it.

Introduction: Many different approaches for the repair of a perineal hernia (PH) after abdomino-perineal rectum amputation (APR) have been described throughout the years. Literature shows us that the use of a mesh had the best results with relatively low rates of recurrence compared to primary suture. Yet there is still no consensus on the best technique for fixation of the mesh in the perineal cavity. Methods: We want to introduce an addition to the surgical repair technique, using laparoscopic glue to ensure a solid fixation of the mesh. This is to prevent small bowel from sliding into the perineal area due to the high abdominal pressure when standing and to avoid the difficulties and risks of laparoscopical suturing in this area. Results: This use of glue for fixation of the mesh has been successful in the three cases described, with no recurrence after one-year follow-up. Conclusion: A recurrent PH can be prevented by a solid fixation of the mesh using the technique of a glued mesh repair. This technique shows to be easy, fast and without recurrence.

Molecular detection of Leptospira sp. in cattle and goats in Kelantan, Malaysia after a massive flood using multiplex polymerase chain reaction.

Flood is a potential driver in spreading waterborne diseases including leptospirosis, which is a zoonotic disease caused by pathogenic bacteria of the genus Leptospira. In the case of leptospirosis, cattle and goats can be incidental hosts and potential carriers of leptospirosis. Traditionally, serology such as microscopic agglutination test (MAT) and isolation of the organisms have been commonly used as the diagnostic approaches in diagnosing leptospirosis. However, nowadays, various molecular techniques have been developed for specific detection of Leptospira sp. such as, polymerase chain reaction (PCR), which is sensitive, specific and rapid in detecting the species. This study detected Leptospira sp. directly from the blood and urine of the animals such as, cattle, goats and sheep in Kelantan after a massive flood by using multiplex PCR (mPCR). From the results collected in the study, four blood samples (0.63%; 4/635) were found to be positive with Leptospira sp. and one urine sample (3.23%; 1/31) was detected as positive with Leptospira sp. The blood and urine samples that were detected to be positive with Leptospira sp. were collected from cattle and goats exposed to the flood. However, no Leptospira sp. was detected from the sheep in this study. Multiplex PCR (mPCR) was successfully used to detect the presence of Leptospira sp. in animals. Apart from that, it is also suggested that flood has a significant role in transmitting the disease to animals.

Toxoplasma gondii infection in native village chickens (Gallus domesticus) in Selangor and Melaka, Malaysia.

Toxoplasmosis is a worldwide zoonosis caused by the protozoa Toxoplasma gondii which affects human and animals. Village chickens (Gallus domesticus) most commonly known as Ayam Kampung or free-range chickens, have been suggested to play a role in the epidemiology of toxoplasmosis. This study determines the presence of T. gondii in the village chicken populations in two states of Malaysia. A total of 50 serum samples from the chickens from Selangor (n=20) and Melaka (n=30) were collected and analysed using commercial serological kits. T. gondii antigen was detected in 20% (Selangor 30%; Melaka 13%) samples using ELISA test and anti-T. gondii antibody was detected in all positive ELISA samples using the indirect haemagglutination test (IHAT). Histopathological examination revealed tissue changes such as inflammation and degeneration in brain and liver of seropositive chickens. This is the first report of T. gondii infection in the village chickens in Malaysia.

Molecular detection of Leptospira sp. in cattle and goats in Kelantan, Malaysia after a massive flood using multiplex polymerase chain reaction

@#Flood is a potential driver in spreading waterborne diseases including leptospirosis, which is a zoonotic disease caused by pathogenic bacteria of the genus Leptospira. In the case of leptospirosis, cattle and goats can be incidental hosts and potential carriers of leptospirosis. Traditionally, serology such as microscopic agglutination test (MAT) and isolation of the organisms have been commonly used as the diagnostic approaches in diagnosing leptospirosis. However, nowadays, various molecular techniques have been developed for specific detection of Leptospira sp. such as, polymerase chain reaction (PCR), which is sensitive, specific and rapid in detecting the species. This study detected Leptospira sp. directly from the blood and urine of the animals such as, cattle, goats and sheep in Kelantan after a massive flood by using multiplex PCR (mPCR). From the results collected in the study, four blood samples (0.63%; 4/635) were found to be positive with Leptospira sp. and one urine sample (3.23%; 1/31) was detected as positive with Leptospira sp. The blood and urine samples that were detected to be positive with Leptospira sp. were collected from cattle and goats exposed to the flood. However, no Leptospira sp. was detected from the sheep in this study. Multiplex PCR (mPCR) was successfully used to detect the presence of Leptospira sp. in animals. Apart from that, it is also suggested that flood has a significant role in transmitting the disease to animals.

Toxoplasma gondii infection in native village chickens (Gallus domesticus) in Selangor and Melaka, Malaysia

@#Toxoplasmosis is a worldwide zoonosis caused by the protozoa Toxoplasma gondii which affects human and animals. Village chickens (Gallus domesticus) most commonly known as Ayam Kampung or free-range chickens, have been suggested to play a role in the epidemiology of toxoplasmosis. This study determines the presence of T. gondii in the village chicken populations in two states of Malaysia. A total of 50 serum samples from the chickens from Selangor (n=20) and Melaka (n=30) were collected and analysed using commercial serological kits. T. gondii antigen was detected in 20% (Selangor 30%; Melaka 13%) samples using ELISA test and anti-T. gondii antibody was detected in all positive ELISA samples using the indirect haemagglutination test (IHAT). Histopathological examination revealed tissue changes such as inflammation and degeneration in brain and liver of seropositive chickens. This is the first report of T. gondii infection in the village chickens in Malaysia.

Prevalence and characteristics of cigarillo smoking in Canada: results from the Canadian Tobacco Use Monitoring Survey.

OBJECTIVES: Cigarillo smoking has been associated with many adverse outcomes; however, little is known about its use in Canada. The aim of this study was to assess the prevalence and characteristics of ever and the current use of cigarillo in Canada. STUDY DESIGN: This study was a cross-sectional study. METHODS: This study was a secondary data analysis of the 2012 cycle of the Canadian Tobacco Use Monitoring Survey collected by Statistics Canada, examining tobacco use among Canadians aged 15 years or older in all 10 provinces. The two main outcomes of the present study were 'ever use' and 'current use' of cigarillos. Covariates examined included the following: demographic factors, socio-economic factors, and smoking-related factors. RESULTS: The overall prevalence of ever and current cigarillo smoking were 38.4% and 3.1%, respectively. Factors that had the highest association with cigarillo smoking included being a male and being young. Cigarette and marijuana use were also associated with increased use of cigarillo. Specifically, marijuana users were at two-fold increase of the current cigarillo smoking (odds ratio = 2.18, 95% confidence interval: 1.97-2.41). CONCLUSIONS: This study highlights the importance of correcting public perception about cigarillos and directing government resources to prevent an increase in their use.

Osseous Metaplasia in a Free-living Snake (Patagonian Green Racer; Philodryas patagoniensis) in Brazil, 2012.

We describe an osseous metaplasia in a wild Patagonian green racer (Philodryas patagoniensis). The 5.5×1.5-cm lesion of irregular contour on the right dorsolateral surface proximal to the snake's cloaca was raised, hard, ulcerated centrally, and radiopaque and interfered with mobility. Microscopy revealed osseous metaplasia on skin and muscle.

Case-control investigation on the risk factors of melioidosis in small ruminant farms in Peninsular Malaysia.

AIMS: Epidemiology of melioidosis is poorly understood because its occurrence is influenced by complex interaction of environmental, climatic, physicochemical and host factors. We investigated the potential risk factors for the exposure to Burkholderia pseudomallei in small ruminants' farms in Peninsular Malaysia. METHODS AND RESULTS: Melioidosis-positive (n = 33) and negative (n = 27) farms were selected and visited for interviews and environmental samples collection. The characteristics and putative disease risk factors were compared between the case and the control farms using Chi-square test and logistic regression analysis. The multivariable logistic regression analysis showed that the odds of melioidosis were significantly higher in farms that had bush clearing around farms (odds ratio (OR) = 6.61, 95% confidence interval (CI) = 1.12-38.84, P = 0.037), in farms with B. pseudomallei present in the soil (OR = 6.23, 95% CI = 1.03-37.68, P = 0.046), in farms that have other animal species present (OR = 7.96, 95% CI = 1.14-55.99, P = 0.037) and in farms that had flooding or waterlogging conditions (OR = 11.95, 95% CI = 1.39-102.6, P = 0.024) when compared to the odds of the disease in farms that did not have the above conditions. The odds of the disease in farms that treated their soils with lime were significantly lower (OR = 0.028, 95% CI = 0.003-0.29, P = 0.003) compared to the odds in those that did not. CONCLUSIONS: The risk factors for the exposure to B. pseudomallei highlighted above may have contributed to the occurrence of melioidosis in animals in the study farms. SIGNIFICANCE AND IMPACT OF THE STUDY: Information from the study may be helpful in planning control measures against melioidosis and have improved understanding of the epidemiology of the disease in livestock farms.

Nasal Bubble CPAP: One Year Experience in a Neonatal Unit of a Tertiary Health Facility in Northwestern Nigeria.

AIMS AND OBJECTIVES: Nasal bubble continuous positive airway pressure (NBCPAP) respiratory support, though decades old, is beginning to gain popularity in developing countries including Nigeria. We reviewed neonates who benefitted from NBCPAP, to describe the demographics and outcome of NBCPAP respiratory support in newborns admitted to the neonatal unit of Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, over a one year period. MATERIALS AND METHODS: The study is a descriptive observational review of all neonates who required NBCPAP respiratory support in the neonatal unit of ABUTH Zaria. Data was extracted from a specifically designed proforma used to obtain information on each neonate throughout the period of admission. RESULTS: Twenty babies received NBCPAP respiratory support during the period of study. Seventeen (85%) of the neonates were successfully weaned off CPAP while three (15%) failed CPAP. Three neonates developed complications with two having CPAP belly syndrome and the third had facial swelling which resolved spontaneously after 6 hours. Overall, seven (41%) of the neonates who were successfully weaned off CPAP were discharged home. CONCLUSION: MajorityofnewbornswhorequirerespiratorysupportwillbenefitfromNBCPAP therefore, this method of respiratory support should be popularized and neonatal units in the country should be supported to efficiently offer the service.

The prevalence and distribution of Brucella melitensis in goats in Malaysia from 2000 to 2009.

A study was conducted to describe the prevalence and distribution of zoonotic Brucella melitensis in goats in Peninsular Malaysia. Using serosurveillance data of the last decade (2000-2009) involving 119,799 goats and 3555 farms, the seroprevalence of brucellosis among goats was 0.91% (95% CI=0.86-0.96) and among farms was 7.09% (95% CI=6.27-7.98). The odds of brucellosis was significantly (P<0.05) higher in the later part of the decade, in larger herd size and among the states located in the peninsula as compared to eastern Malaysia. The infection was detected throughout Malaysia but at generally low seroprevalences with states like Perlis that border neighbouring countries having higher seroprevalence of brucellosis than other non-border states.

Outcome of Extremely Low Birth Weight Babies in Zaria; A Ten-Year Review.

BACKGROUND: Survival among extremely low birth weight (ELBW) babies (birth weight below 1000grams) in resource limited settings is still very low. The study aimed to determine the correlation between materno-foetal factors and outcome in this category of neonates. STUDY DESIGN: A retrospective study in which patients' records admitted into the Neonatal Unit of Ahmadu Bello University Teaching Hospital between January 2005 and December 2014 were retrieved. Information on neonates weighing < 1000 g were extracted and analyzed. Survival at discharge was the primary outcome. RESULTS: The overall survival rate of extremely low birth weight babies was 18%. Mortality in ELBW neonates weighing less than 750g was 100%. Factors that were significantly predictive of survival were birth weight, parity and duration of hospital stay with p-values of 0.014, 0.039 and 0.025 respectively CONCLUSION: The survival rate of ELBW babies remains low in our resource constrained setting. Focus should be on preventing preterm deliveries and as well equipping newborn care providers and newborn units with the necessary skills and materials respectively to enable implementation of evidence based interventions to improve newborn survival.

Chromosome analysis in embryos from young patients with previous parity.

This study included 173 young couples of proven fertility who had previously undergone preimplantation genetic screening for chromosomes X and Y for family balancing. Several months later, when the outcome of the pregnancies was already known, the blastomeres from the corresponding embryos transferred were reanalysed by fluorescence in-situ hybridization (FISH) for chromosomes 13, 16, 18, 21, 22 with the aim of investigating correlation with embryo viability and the level of FISH sensitivity (embryos confirmed to be euploid). According to the results, informative in 152 couples, the proportion of euploid embryos was significantly lower in 53 nonpregnant women when compared with 99 women with term pregnancy (49% versus 75% respectively, P < 0.001). In addition, in 21 nonpregnant patients, all embryos transferred were found to be chromosomally abnormal. The level of FISH sensitivity was calculated in the group of term pregnancies where the number of euploid embryos was expected to exceed or match with the number of babies born. The resulting false-negative rate was 4.0% per patient and 1.9% per embryo. These findings confirmed the limited prediction power of embryo morphology on implantation but also the relevance of chromosomal abnormalities in causing embryo demise.

Active infection and morphometric study of Trypanosoma evansi among horses in Peninsula Malaysia.

Apart from occasional reports of clinical disease affecting horses, there is no information about Trypanosoma evansi in horses in Peninsula Malaysia. Thus, a cross-sectional study was conducted in eight states in Peninsula Malaysia to determine the active presence of T. evansi in horses. A total of 527 blood samples were obtained and examined by haematocrit centrifugation technique (HCT), Giemsa-stained thin blood smear (GSS), morphometric measurements, polymerase chain reaction (PCR) and cloning of PCR products. The results showed an overall parasitological prevalence of 0.57% (3/527, CI: 1.6-0.19%) with both HCT and GSS. Morphometric study revealed the mean total length of the trypanosomes including the free flagellum was 27.94 ± 2.63 µm. PCR successfully amplified a trypanosome specific 257 bp in 1.14% of samples (6/527, CI: 2.4-0.52%) and was confirmed by nucleotide sequences. The mean packed cell volume (PCV) for the positive cases detected by HCT was lower (23% ± 7.00) compared to the positive cases detected by PCR alone in the state of Terengganu (35% ± 4.73). In conclusion, this study showed T. evansi infection occurred in low frequency in horses in Peninsula Malaysia, and anaemia coincided with parasitaemic animals. PCR is considered as a sensitive diagnostic tool when parasitaemia is undetectable. The slight lengthier mean of parasite and anaemia may indicate a virulent strain of T. evansi circulating throughout the country. Thus, it's highly recommended to shed light on host-parasite relationship for better epidemiological understanding.