Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

Introduction: To describe the duration of survival among bone tumour patients with endoprosthesis reconstruction and to determine frequency of implant failure, revision of surgery, and amputation after endoprosthesis reconstruction. Materials and methods: A retrospective cross-sectional review of all patients with either primary bone tumour or secondary bone metastases treated with en bloc resection and endoprosthesis reconstruction from January 2008 to December 2020. Results: A total of 35 failures were recorded among the 27 (48.2%) patients with endoprostheses. Some of the patients suffered from one to three types of modes of failure on different timelines during the course of the disease. Up to eight patients suffered from more than one type of failure throughout the course of the disease. Out of all modes of failure, local recurrence (type 5 failure) was the most common, accounting for 25.0% of all failure cases. Four patients (7.1%) eventually underwent amputation, which were either due to infection (2 patients) or disease progression causing local recurrence (2 patients). Conclusion: The overall result of endoprosthesis reconstruction performed in our centre was compatible with other centres around the world. Moreover, limb salvage surgery should be performed carefully in a selected patient group to maximise the benefits of surgery.

Post-COVID-19 conditions encompass a wide range of health problems, including enteritis, but their association with parasitic infections has not yet been investigated. This study analyzed gastrointestinal symptoms, medical histories, fecal Cryptosporidium oocysts, and the history of COVID-19 infection in patients who attended the Faculty of Medicine, Cairo University, from January to July 2021. Fecal biomarkers, including H. pylori, occult blood, fecal calprotectin (FCAL), and TNF-a, were measured, and Cryptosporidium spp. genotypes were molecularly characterized among post-COVID-19 patients using RFLP. Preliminary results from 210 post-COVID-19 patients revealed that group 1 (Cryptosporidiumpositive) (n = 49) and group 2 (Cryptosporidium-negative) (n = 161) showed no significant difference in the prevalence rate of diabetes mellitus (DM). While group 2 was linked to diarrhea, only infections with Cryptosporidium post-COVID-19 were related to chronic diarrhea, vomiting, and weight loss. A total of 220 healthy subjects served as negative controls. Administering azithromycin, hydroxychloroquine, and ivermectin was significantly related to an increased risk of Cryptosporidium infection in group 1, whereas only azithromycin was more frequently recorded in group 2. Antioxidant supplementation insignificantly affected the incidence of cryptosporidiosis. Cryptosporidiosis with a history of COVID-19 was linked to H. pylori infections, increased inflammatory biomarkers (FCAL and TNF-a), and occult blood when compared with group 2. Cryptosporidium genotype 1 was the most commonly occurring subset in individuals with post-COVID-19. The findings demonstrated that aggravating gastrointestinal manifestations, increased fecal biomarkers and anti-COVID-19 therapeutic interventions are significantly related to the existence of Cryptosporidium oocysts in patients with post-COVID-19, indicating the predominance of.

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.

Introduction: To investigate the use of a tubular retractor to provide access to the craniovertebral junction (CVJ) sparing the soft palate with the aim of reducing complications associated with traditional transoral approach but yet allowing adequate decompression of the CVJ. Materials and methods: Twelve consecutive patients with severe myelopathy (JOA-score less than 11) from ventral CVJ compression were operated between 2014-2020 using a tubular retractor assisted transoral decompression. Results: All patients improved neurologically statistically (p=0.02). There were no posterior pharynx wound infections or rhinolalia. There was one case with incomplete removal of the lateral wall of odontoid and one incidental durotomy. Conclusions: A Tubular retractor provides adequate access for decompression of the ventral compression of CVJ. As the tubular retractor pushed away the uvula, soft palate and pillars of the tonsils as it docked on the posterior pharyngeal wall, the traditional complications associated with traditional transoral procedures is completely avoided.

Objective: DiGeorge Syndrome (DGS) is a common multisystem disorder associated with deletions on chromosome 22q11.2. Our objective is to evaluate the psychiatric comorbidities and demographics of patients suffering from DGS in a nationally representative dataset on inpatient hospitalizations. Methods: The Nationwide Inpatient Sample for the year 2005−2017 was used for this study. Data on patients with DiGeorge syndrome were collected by using the International Classification of Diseases code. Univariate and multivariate logistic regression analysis was performed. Results: In our study, the average age was 30.4 years (n = 6,563), with 59.9% male, and 61.8% of patients were white. There was a high prevalence of mood disorders (24.7%) and anxiety disorders (16.4%), followed by schizophrenia and other psychotic condition (14.0%). In patients with mood disorders, 8% had Major Depressive Disorder, and 7% had bipolar depression. Overall composite of psychiatric comorbidities was present in 2,959 (45.1%) of patients. The mean length of stay was 6.58 days, and 77% of patients had routine discharge to home. In the adjusted analysis, the average length of stay was 8.6 days vs. 6.7 days (p ＜ 0.001) in patients with and without psychiatry comorbidities.In comparison to routine discharge, patients with psychiatry comorbidities were more likely to be discharged to other healthcare facilities (odds ratio [OR]: 1.28, p ＜ 0.001) and discharged against medical advice (OR: 3.45, p ＜ 0.001). Conclusion Patients with DGS have worse outcomes with a higher rate of discharge to other healthcare facilities and a higher rate of being discharged against medical advice. Further large scale randomize studies are indicated.

Through the regional control programme, Malaysia has been successfully reducing the incidence of Plasmodium falciparum and Plasmodium vivax infections. However, the incidence of zoonotic malaria Plasmodium knowlesi infection is increasing and now has been the major cause of malaria in Malaysia especially Malaysian Borneo. The emergence of knowlesi infection has threatened the malaria elimination programme which the government aims to reduce the overall malaria infections by 2020. Unlike other benign human Plasmodium spp., P. knowlesi can cause fatal infections. The aim of this study was to determine the incidence and distribution of five human malaria parasites including P. knowlesi in Peninsular Malaysia and Malaysian Borneo. A total of 112 blood samples were collected from seven states and district hospitals in Peninsular Malaysia and Malaysian Borneo from year 2015 to 2016. The samples were examined by microscopy and further confirmed by nested PCR assay targeting 18S rRNA gene of Plasmodium spp. Following the nested PCR assays, a total of 54 (48.2%) samples were positive for P. knowlesi infections, 12 (10.7%) cases were positive for P. vivax infections, followed by 7 (6.3%) cases of P. falciparum and 4 (3.5%) cases of P. malariae. There were 3 cases (2.7%) of mixed infections (P. knowlesi/P. vivax). However, no cases were identified as P. ovale. A total of 32 (28.6%) cases were found as negative infections. LoopMediated Isothermal Amplification Assay (LAMP) was performed to confirm inconclusive results produced by microscopy and nested PCR. P. knowlesi showed the highest prevalence in Sarawak (n= 30), Sabah (n=13), Pulau Pinang (n=5) and Pahang (n=6). PCR and LAMP was not able to detect a large number of microscopy positive samples due to DNA degradation during storage and shipping. Among all the states involved in this study, the highest prevalence of P. knowlesi infection was found in Sabah and Sarawak.

Introduction: To compare the anxiety levels demonstrated by children during cast removal procedure between oscillating saw vs cast shear methods. Material and methods: A randomised prospective study of 102 children (mean age 8.3 ± 3.5 years) with fractures involving upper or lower limbs. Children undergoing removal of cast were divided into 2 groups; either by an oscillating saw or a cast cutting shear. The level of anxiety was assessed by recording the heart rate with a portable fingertip pulse oximeter before, during and after removal of the cast. Objective assessment was performed by documenting the fear level on Children’s Fear Scale (CFS). Results: There was a significant increase in the heart rate of children during cast removal while using the oscillating saw compared to cast shear (p<0.05). The noise level produced by the saw exceeded 80 dB (mean 103.3 dB). The fear level was significantly lower in the cast shear group (p<0.05). Conclusion: The noise produced by the oscillating saw was associated with an increased anxiety level in children undergoing cast removal. Cast shear is a simple and inexpensive instrument that can be used for cast removal in overly anxious children.

Femoral neck stress fractures are rare in children. To the best of our knowledge, the tension type stress fracture has been reported only twice in the English language literature. We report on a five years follow-up of a 10-year-old boy with this injury which was initially missed. The fracture healed after screw fixation. We highlight the importance of considering stress fracture as a differential diagnosis in a child with chronic hip pain. A careful physical examination and the appropriate imaging will avoid missing the diagnosis.