Rhipicephalus microplus, known as the hard tick, is a vector for the parasites Babesia spp. and Anaplasma marginale, both of which can cause significant financial losses to the livestock industry. There is currently no effective vaccine for R. microplus tick infestations, despite the identification of numerous prospective tick vaccine candidates. As a result, the current research set out to develop an immunoinformatics-based strategy using existing methods for designing a multi-epitope based vaccination that is not only effective but also safe and capable of eliciting cellular and humoral immune responses. First, R. microplus proteins Bm86, Subolesin, and Bm95 were used to anticipate and link B and T-cell epitopes (HTL and CTL) to one another. Antigenicity testing, allergenicity assessment, and toxicity screening were just a few of the many immunoinformatics techniques used to identify potent epitopes. Multi-epitope vaccine design was chosen based on the antigenic score 0.935 that is promising vaccine candidate. Molecular docking was used to determine the nature of the interaction between TLR2 and the vaccine construct. Finally, molecular dynamic simulation was used to assess the stability and compactness of the resulting vaccination based on docking scores. The developed vaccine was shown to be stable, have immunogenic qualities, be soluble, and to have high expression by in silico cloning. These findings suggest that experimental investigation of the multi-epitope based vaccine designed in the current study will produce achievable vaccine candidates against R. microplus ticks, enabling more effective control of infestations.

Purpose: Our study aimed to evaluate the risk and benefit profiles of clinical trials using abiraterone in cancer treatment. Materials and Methods: A comprehensive search was conducted on May 24, 2023, using databases such as PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov. We extracted data on adverse events, progression-free survival, overall survival, objective response rate (ORR), and prostate-specific antigen response rate (PSA-RR). The Common Terminology Criteria for Adverse Events were used to assess risks, while ORR and PSA-RR were used to assess benefits. Trials were categorized as positive, negative, or indeterminate based on their safety profiles and efficacy outcomes. Results: Nearly all clinical trials testing abiraterone in prostate cancer showed promising outcomes with 89% of studies meeting their endpoint. Our study supports abiraterone’s use in prostate cancer, its only U.S. Food and Drug Administration-approved indication to treat, with a median ORR of 20.0% and a median PSA-RR of 42.0%. However, when looking at the 3 novel indications tested, the risk-to-benefit profile was similar to that of its original approval. Even though most novel indications failed to meet their primary endpoint, the overall toxicity profile was similar to that found in prostate cancer. Conclusion Abiraterone showed an overall risk-to-benefit portfolio that supports the use of its treatment in prostate cancer. Although the primary endpoints in ovarian and breast cancer trials were not met, the use was appropriate when assessing how the mechanism of action for abiraterone could be beneficial in patients with these types of cancers.

Purpose: Our study aimed to evaluate the risk and benefit profiles of clinical trials using abiraterone in cancer treatment. Materials and Methods: A comprehensive search was conducted on May 24, 2023, using databases such as PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov. We extracted data on adverse events, progression-free survival, overall survival, objective response rate (ORR), and prostate-specific antigen response rate (PSA-RR). The Common Terminology Criteria for Adverse Events were used to assess risks, while ORR and PSA-RR were used to assess benefits. Trials were categorized as positive, negative, or indeterminate based on their safety profiles and efficacy outcomes. Results: Nearly all clinical trials testing abiraterone in prostate cancer showed promising outcomes with 89% of studies meeting their endpoint. Our study supports abiraterone’s use in prostate cancer, its only U.S. Food and Drug Administration-approved indication to treat, with a median ORR of 20.0% and a median PSA-RR of 42.0%. However, when looking at the 3 novel indications tested, the risk-to-benefit profile was similar to that of its original approval. Even though most novel indications failed to meet their primary endpoint, the overall toxicity profile was similar to that found in prostate cancer. Conclusion Abiraterone showed an overall risk-to-benefit portfolio that supports the use of its treatment in prostate cancer. Although the primary endpoints in ovarian and breast cancer trials were not met, the use was appropriate when assessing how the mechanism of action for abiraterone could be beneficial in patients with these types of cancers.

Purpose: Our study aimed to evaluate the risk and benefit profiles of clinical trials using abiraterone in cancer treatment. Materials and Methods: A comprehensive search was conducted on May 24, 2023, using databases such as PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov. We extracted data on adverse events, progression-free survival, overall survival, objective response rate (ORR), and prostate-specific antigen response rate (PSA-RR). The Common Terminology Criteria for Adverse Events were used to assess risks, while ORR and PSA-RR were used to assess benefits. Trials were categorized as positive, negative, or indeterminate based on their safety profiles and efficacy outcomes. Results: Nearly all clinical trials testing abiraterone in prostate cancer showed promising outcomes with 89% of studies meeting their endpoint. Our study supports abiraterone’s use in prostate cancer, its only U.S. Food and Drug Administration-approved indication to treat, with a median ORR of 20.0% and a median PSA-RR of 42.0%. However, when looking at the 3 novel indications tested, the risk-to-benefit profile was similar to that of its original approval. Even though most novel indications failed to meet their primary endpoint, the overall toxicity profile was similar to that found in prostate cancer. Conclusion Abiraterone showed an overall risk-to-benefit portfolio that supports the use of its treatment in prostate cancer. Although the primary endpoints in ovarian and breast cancer trials were not met, the use was appropriate when assessing how the mechanism of action for abiraterone could be beneficial in patients with these types of cancers.

Purpura fulminans (PF) is a severe clinical manifestation of Neisseria meningitides infection that is associated with high mortality rates in children. Survivors are frequently left with debilitating musculoskeletal sequelae. There is a paucity of reports on the musculoskeletal pathology of purpura fulminans. We report on a 2-year-old boy with purpura fulminans due to meningococcemia. The child developed distal gangrene in both the upper and lower limbs. Amputations were done for both lower limbs. Histological examination of the amputated specimens showed an inflammatory process and features of osteonecrosis. The latest follow-up at the age of 6 years showed a right knee valgus due to asymmetrical growth arrest of the proximal tibia. PF and its complications are challenging to treat and may require a multidisciplinary approach to improve patient’s functional ability.

Tibial tuberosity avulsion fracture is a rare injury, and bilateral occurrence is more uncommon. Periosteal sleeve fracture is a unique fracture pattern which was first described in the lower pole of patella in children. We are reporting a rare case of bilateral tibial tuberosity sleeve fracture in a teenage boy which occurred while sprinting. The patient underwent open reduction, pull through suture fixation of the bilateral tibial tuberosity and screw fixation of left tibial tuberosity. Post-operative rehabilitation included gradual increment of range of motion with hinged brace and quadriceps muscle strengthening. Close follow-up was done to monitor the progression of his recovery. At six months follow-up, the patient recovered well. Both knees had full range of motion with an intact extensor mechanism.

Anaplasma marginale is the most prevalent tick-borne haemoparasite of cattle and causes huge economic losses to the dairy industry worldwide. This study aimed to determine the occurrence of A. marginale infection in blood and tick samples collected from livestock animals in the districts located in Khyber Pakhtunkhwa (KPK), Pakistan. A total of 184 blood and 370 tick samples were included in this study. It has never been reported that sheep, goats, and cattle in Tank, Ghulam Khan, Birmil and Miran Shah areas were infected with A. marginale. All samples of blood and ticks were collected through random sampling from March 2021 to January 2022 from cattle, sheep and goats and screened through PCR for anaplasmosis by using primer pairs of Anaplasma spp. Three hundred and seventy ticks were collected from infested hosts (120/184, 64.21%). Among the four morphologically identified tick species, the highest occurrence was recorded for Rhipicephalus sanguineus (n=138, 37.29%), followed by Rhipicephalus microplus (n=131, 35.4%), Rhipicephalus annulatus (n=40, 10.81%), Hyalomma anatolicum (n=31, 8.37%), and Hyalomma marginatum (n=30, 8.1%). The occurrence of female tick was highest (n=160, 43.24%), followed by nymphs (n=140, 37.38%) and males ticks (n=70, 18.9%). Among these ticks, A. marginale was detected in female ticks of R. microplus, and R. sanguineus. Molecular identification of A. marginale was confirmed in 120 out of 184 blood samples and 6 out of 74 tick samples. Overall, occurrence of A. marginale in blood and tick samples was found to be 65.21% and 8.1% respectively. Species-wise occurrence in blood samples of goats were 71.11% followed by sheep 68.31% and cattle 50%. Specie-wise occurrence of A. marginale in tick samples of cattle were 12.5% followed by goats 6.89%. The obtained sequence showed similarity with A. marginale reported from Kenya and USA. We report the first PCR based detection of A. marginale infection in blood samples and in R. sanguineus ticks of goats simultaneously.

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

Histone modifications have been demonstrated to play a significant role in oral squamous cell carcinoma (OSCC) epigenetic regulation. An in-silico analysis of The Cancer Genome Atlas (TCGA) of various histone acetyl transferases (HATs) and histone deacetylases (HDACs) suggested that HATs do not differ between normal and tumor samples whereas HDAC2 and HDAC1 change maximally and marginally respectively between normal and tumor patients with no change being noted in HDAC6 expression. Hence, this investigation was carried out to validate the expression states of HDAC 1, 2 and 6 mRNAs in buccal mucosa and tongue SCC samples in an Indian cohort. Buccal mucosa and tongue squamous cell carcinoma tissues with intact histopathology were processed for RNA isolation followed by cDNA synthesis which was then subjected to q-PCR for HDACs. The average RNA yield of the tongue tissue sample was ∼2 μg/mg of tissue and the A260/280 ratios were between 2.03 and 2.06. The average RNA yield of buccal mucosa tissue sample was ∼1 μg/mg of tissue and the A260/280 ratio were between 2.00 and 2.08. We have demonstrated that HDAC2 was overexpressed in tongue and buccal mucosa samples. Over-expression of HDAC2 imply potential use of HDACi along with standard chemotherapeutic drug in oral cancer treatment.