Orotic acid, a promoter of liver carcinogenesis induces DNA damage in rat liver

Orotic acid, a precursor of pyrimidine nucleotide biosynthesisand a promoter for liver carcinogenesis, when fed at 1% levelin a diet for 5 weeks resulted in liver DNA damage. The damagecan be monitored as alkali-labile lesions using alkaline sucrosegradients as well as alkaline elution technique. Furthermore,the induced DNA damage persists for up to three weeks afterwithdrawal of the orotic acid diet. The fad that several skin-tumourpromoters also induce DNA damage raises the question whetherDNA damage is a component in tumour promotion.     

Severe, intractable headache after injection with botulinum a exotoxin: report of 5 cases.

BACKGROUND: Botulinum A exotoxin is a safe agent in common use in dermatology. Occasionally, patients receiving botulinum toxin injections report postprocedure discomfort, including headaches. OBJECTIVE: Our purpose was to estimate the rate of severe headaches occurring after injection with botulinum toxin for dermatologic indications. METHODS: We used prospective monitoring of botulinum toxin injection outcomes in a single-site, 3-dermatologist practice. There was in-office and telephone follow-up of patients experiencing severe headaches. RESULTS: Approximately 1% of patients (4/320) receiving botulinum A exotoxin injections may experience severe, debilitating headaches. These may persist at high intensity for 2 weeks to 1 month before gradually fading. CONCLUSION: Botulinum A exotoxin injection may be associated with the development of life-altering headaches. Patients should be informed of this possibility.     

Pegylated interferon-based sequential therapy for treatment of HBeAg reactive pediatric chronic hepatitis B—First study in children

Background

Our aim was to evaluate the efficacy and safety of sequential therapy using pegylated interferon (Peg-IFN) and nucleos(t)ide analogue (NA) for treatment of children in immunoactive (IA) and immunotolerant (IT) phases of chronic hepatitis B.

Methods

It was a prospective observational study where those willing for sequential therapy were allocated to group 1 (sequential therapy) and others to group 2 (standard therapy). Sequential therapy included 8 weeks of NA followed by 44 weeks of combination of NA and Peg-IFN. In group 2, IA children received NA monotherapy, and IT children received no therapy. HBe seroconversion, HBs seroconversion, and loss of HBV DNA were the major outcome measures.

Results

A total of 61 children (36 IA and 25 IT) were included in the analysis. Among the IA children, 17 received sequential therapy and 19 received standard therapy; whereas, among the IT children, 12 received sequential therapy and 13 did not receive any therapy. In IA phase, sequential therapy led to higher HBe seroconversion (64.7% vs. 21.05%, p =?0.017) and higher virological clearance (94.12% vs. 52.63%, p =?0.008). In IT children, there was no benefit of treatment with sequential therapy over observation alone. Baseline ALT >?100 IU/L predicted response to therapy with 100% sensitivity, 89.5% specificity, and LR⁺ of 9.52.

Conclusion

Sequential therapy leads to higher HBe seroconversion and virological response in children in IA phase. Children with baseline ALT >?100 IU/mL are more likely to respond to sequential therapy. There appears to be no role of sequential therapy in children in IT phase.

     

Immune system response during viral Infections: Immunomodulators,cytokine storm (CS) and Immunotherapeutics in COVID-19

Coronaviruses are non-segmented and single stranded positive-sense RNA (+ssRNA) viruses. To date, 06 human coronaviruses (HCoVs) are reported; α-CoVs (HCoVs-NL63 and HCoVs-229E) and β-CoVs (HCoVs-OC43, HCoVs-HKU1, SARS-CoV, MERS-CoV). While, novel coronavirus (SARS-CoV-2) is the most recent member. The genome sequence of SARS-CoV-2 is 82% similar to SARS–COV-1. The compelling evidences link the progression of viral infection of SARS-CoV-2 with excessive inflammation as a result of the exaggerated immune response and elevated production of “immunocytokines” resulting in cytokine storm (CS); followed by a series of events, like acute organ damage, acute respiratory distress syndrome (ARDS) as well as death. Hence attempts to reduce cytokine storm are now being considered as a new paradigm shift in the clinical management of SARS-CoV-2. Tocilizumab (IL-6 blocker), Baricitinib (JAKs and AAK1 inhibitor), TNFα inhibitors (Infliximab, Adalimumab, Certolizumab) are currently being evaluated for possible block of the CS. Hence, rationalizing anti-inflammatory therapeutics would be the most judicious approach for significant reduction in COVID-19 mortality. In order to elucidate optimized and rationaled use of different therapeutics in COVID-19, we collated latest available information from emerging scientific evidences, integrated previous attempts as well as clinical successes, and various adopted approaches to mitigate past outbreaks with of SARS-CoV and MERS CoV.     

The Banff Patellar Instability Instrument: validity and reliability of an Indonesian version

Background

The Banff Patellar Instability Instrument (BPII) is a valuable scoring tool for assessing patellofemoral instability in patients suffering from patellofemoral pain syndrome (PFPS). The BPII 2.0 is a shortened version of the BPII. However, there is no Indonesian edition of BPII 2.0 that has been validated. This study aimed to determine the validity and reliability of the Indonesian version of the BPII 2.0.

Materials and methods

This was a cross-sectional study that used a forward–backward translation protocol to create an Indonesian version of the BPII 2.0. Thirty patients with PFPS were given the questionnaires. The questionnaire's validity was evaluated by analyzing the correlation between score of each subscale and the overall score to the Indonesian version of the Kujala score using Pearson correlation coefficient, while the reliability was evaluated by measuring the internal consistency (Cronbach α) and test–retest reliability (intraclass correlation coefficient).

Results

The Indonesian version of BPII 2.0 and the Indonesian version of Kujala score had a strong Pearson correlation coefficient for construct validity. For all subscales, Cronbach α was 0.90–0.98, indicating adequate internal consistency. The test–retest reliability was high, with intraclass correlation coefficient ranging from 0.89 to 0.98 for all subscales. There was no difference in the Indonesian version of BPII 2.0 response between the first and second administration of the questionnaire which was taken 7 days afterward.

Conclusion

The Indonesian version of BPII 2.0 was determined to be valid and reliable and is therefore an objective instrument to evaluate patellofemoral instability in patients with PFPS in the Indonesian population.

     

Predators among protectors: overcoming power abuse during humanitarian crisis through effective humanitarian diplomacy and a gender-transformative approach

Sexual exploitation and abuse (SEA) is one of the most depraved crimes against humanity. When carried out by peacekeepers and humanitarian aid workers, it depicts a catastrophic failure of protection bringing harm to the very people the United Nations and international organizations vow to protect. This paper has highlighted the various allegations and incidents of SEA repeatedly happening in conflict-affected countries. Allegations of SEA have since surfaced related to operations in Bosnia, Cambodia, Somalia, Sierra Leone, Liberia, Kosovo, Cote d''Ivoire, Haiti, Sudan, Guinea and the Democratic Republic of Congo. The symptoms of abuse survivors generally resemble those of Post-Traumatic Stress Disorder, and SEA has significant health consequences and poses a severe threat to public health advancement. Based on the literature review, we propose that international and humanitarian organizations must ensure that these offences do not happen in the future by taking appropriate measures. These organizations must prioritize rigorous training on gender equality and values and include a basic mandatory test on gender equality before joining humanitarian missions. Since humanitarian diplomacy encompasses actions carried out by the humanitarian organizations to acquire space from military and political authorities within to function with integrity, we emphasize that strengthening humanitarian diplomacy can play a pivotal role to train the humanitarian workforce on best practices to reduce SEA. Besides, we further propose that women should be allowed to lead from the front; otherwise, true gender equality and issues relevant to gender, including SEA, will be challenging to attain.