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Background: Propolis and honey are natural bee products with wide range of biological and medicinal properties. The study investigated antimicrobial activity of ethyl alcohol extraction of propolis collected from Saudi Arabia (EEPS) and from Egypt (EEPE), and their synergistic effect when used with honey. Single and polymicrobial cultures of antibiotic resistant human pathogens were tested.Material and methods; Staphylococcus aureus (S. aureus),), Escherichia coli (E. coli) and Candida albicans (C.albicans) were cultured in 10-100% (v/v) honey diluted in broth, or 0.08-1.0% (weight/volume) EEPS and EEPE diluted in broth. Four types of polymicrobial cultures were prepared by culturing the isolates with each other in broth (control) and broth containing various concentrations of honey or propolis. Microbial growth was assessed on solid plate media after 24 h incubation.Results; EEPS and EEPE inhibited antibiotic resistant E.coli, and S.aureus, and C.albicans in single and polymicrobial cultures. S.aureus became more susceptible when it was cultured with E.coli or C.albicans or when all cultured together. C.albicans became more susceptible when it was cultured with S.aureus or with E.coli and S. aureus together. The presence of ethyl alcohol or honey potentiated antimicrobial effect of propolis toward entire microbes tested in single or polymicrobial cultures. EEPS had lower MIC toward E.coli and C.albicans than EEPE. When propolis was mixed with honey, EEPS showed lower MIC than EEPE. In addition, honey showed lower MIC toward entire microbes when mixed with EEPS than when it was mixed with EEPE.Conclusion; 1) propolis prevents the growth of the microorganisms in single and mixed microbial cultures, and has synergistic effect when used with honey or ethyl alcohol, 2) the antimicrobial property of propolis varies with geographical origin, and 3) this study will pave the way to isolate active ingredients from honey and propolis to be further tested individually or in combination against human resistant infections.

Aim: Obesity is a major risk factor for diabetic peripheral neuropathy (DPN) in type 2 diabetes (T2D). This study investigated the effect of glucose lowering medication associated with weight change on DPN., Methods: Participants with T2D were grouped based on whether their glucose lowering medications were associated with weight gain (WG) or weight loss (WL). They underwent clinical, metabolic testing and assessment of neuropathic symptoms, vibration perception threshold (VPT), sudomotor function and corneal confocal microscopy (CCM) at baseline and follow-up between 4 and 7 years., Results: Of 76 participants, 69.7% were on glucose lowering medication associated with WG, and 30.3% were on glucose lowering medication associated with WL. At baseline, participants in the WG group had a significantly longer duration of diabetes (p < .01), higher douleur neuropathique en 4 (DN4) score (p < .0001) and VPT (p = .01) compared with those in the WL group. Over a 56-month period, participants in the WG group showed no significant change in body weight (p = .11), HbA1c (p = .18), triglycerides (p = .42), DN4 (p = .11), VPT (p = .15) or Sudoscan (p = .43), but showed a decline in corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) (p < .0001). Participants in the WL group showed a reduction in weight (p = .01) and triglycerides (p < .05), no change in DN4 (p = .30), VPT (p = .31) or Sudoscan (p = .17) and a decline in the corneal nerve branch density (p < .01)., Conclusions: Participants treated with glucose lowering medication associated with weight gain had worse neuropathy and greater loss of corneal nerves during follow-up, compared to patients treated with medication associated with weight loss., (© 2024 The Author(s). Journal of the Peripheral Nervous System published by Wiley Periodicals LLC on behalf of Peripheral Nerve Society.)

Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) impact morbidity and mortality in burn patients, exacerbated by extensive fluid resuscitation required for more than 20% of total body surface area burns. We report a case of a 28-year-old male with severe burns and a TBSA of 49% who presented after a fire incident. The trauma team managed the patient's fluid resuscitation, followed by early burn debridement. A TraumaGuard catheter was used for continuous intra-abdominal pressure (IAP) monitoring. On the second day of admission, a critical IAP of 20 mm Hg was detected, indicative of impending ACS. Immediate intervention with cistracurium and increased sedation reduced the IAP to 9 mm Hg, preventing the progression to ACS. This case demonstrates the importance of routine IAP monitoring in severely burned patients to prevent ACS. Early identification and management of elevated IAP can avert the progression to ACS and reduce the need for more invasive interventions., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Granulomatosis with polyangiitis is a rare systemic disease that causes necrotizing granulomatous inflammation of small- and medium-sized blood vessels. We present the case of a 46-year-old male with medical history significant for chronic sinusitis, prior history of drug abuse, and a recent tooth infection. He was suspected to have infective endocarditis, but further workup revealed diagnostic findings of granulomatosis with polyangiitis. We discuss how the signs and symptoms of granulomatosis with polyangiitis can overlap with infective endocarditis, a pathophysiologically distinct condition with a strikingly similar presentation., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ansari et al.)

Introduction: This study was undertaken to investigate whether sustained rather than a single measure of corneal nerve loss was associated with the onset of diabetic peripheral neuropathy (DPN) and the progression of neuropathic symptoms and deficits in individuals with type 2 diabetes (T2D)., Methods: Participants underwent clinical, metabolic testing and assessment of neuropathic symptoms, vibration perception threshold (VPT), sudomotor function, and corneal confocal microscopy (CCM) at baseline, 1, 2, and 4-7 years. Sustained corneal nerve loss was defined as abnormal corneal nerve fiber density (CNFD, <24 fibers/mm 2 ), corneal nerve branch density (CNBD, <21 branches/mm 2 ), and corneal nerve fiber length (CNFL, <16 mm/mm 2 ) persisting for ≥50% of the study duration., Results: A total of 107 participants with a mean duration of T2D of 13.3 ± 7.3 years, aged 54.8 ± 8.5 years, underwent baseline and follow-up assessments over a median duration of 4 years, ranging from 1 to 7 years. The DPN prevalence at baseline was 18/107 (16.8%), and of the 89 participants without DPN at baseline, 13 (14.6%) developed DPN during follow-up. Approximately half of the cohort had sustained corneal nerve damage, and corneal nerve measures were significantly lower in this group than those without sustained damage ( p  < 0.0001). Sustained corneal nerve damage was associated with the development of DPN ( p  < 0.0001), a progressive loss of vibration perception ( p  ≤ 0.05), an increased incidence of burning pain, numbness, or a combination of both ( p  = 0.01-0.001), and a borderline association with progressive sudomotor dysfunction ( p  = 0.07). Sustained abnormal CNFL effectively distinguished between participants who developed DPN and those who did not (AUC: 76.3, 95% CI: 65.9-86.8%, p  < 0.0001), while baseline and other sustained measures did not predict DPN onset., Conclusion: Sustained abnormal CCM is associated with more severe corneal nerve damage, DPN development, and the progression of neuropathic symptoms and deficits. Regular CCM monitoring may enable the identification of those at greater risk of developing and worsening DPN who may benefit from more aggressive risk factor reduction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ponirakis, Al-Janahi, Elgassim, Homssi, Petropoulos, Gad, Khan, Zaghloul, Ali, Siddique, Mohamed, Ahmed, Dakroury, El Shewehy, Saeid, Mahjoub, Al-Thani, Ahmed, Hussein, Mahmoud, Hadid, Al Obaidan, Salivon, Mahfoud, Zirie, Al-Ansari, Atkin and Malik.)

This study aims to investigate regional and periodic asymmetries in the impact of the outbreak of the Russia-Ukraine war on global equity markets. Employing the event study methodology, the current study examines global stock market reactions within a 61-day window centred around the event day, i.e., February 24, 2022. MSCI equity indices of 47 sample countries have been utilized to ensure uniformity in the index development methodology. They provide broader coverage of global equity markets by including large and mid-cap companies, representing approximately 85% of the free float-adjusted market capitalization for each sampled country. The study extends the event window to 61 days to assess the enduring effects of the war over a relatively longer period. The research delineates regional and periodic asymmetries and posits that the impact of the war on a market is contingent upon its geographical proximity and trade relations with Russia and Ukraine. Additionally, the impact is stronger during a shorter window surrounding the event date but diminishes over the extended period., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Traumatic brain injury (TBI) is a major public health concern, often leading to significant behavioral and cognitive changes with subsequent impairment in daily functioning and personal interactions. The management of TBI involves a multidisciplinary approach. Neuropsychology has emerged as a critical discipline in assessing, diagnosing, treating, and rehabilitating individuals with TBI. Successful management also requires careful consideration of the patient's cognitive status. Therefore, clinicians must have a comprehensive understanding of the overall clinical picture of the patient at the cognitive and physical level. The primary aim of this research is to explore the role of neuropsychology in TBI management and rehabilitation thoroughly while providing an updated review of the literature. Various neuropsychological assessment tools used to evaluate cognitive functioning in individuals with TBI will be discussed in addition to their validity, reliability, and usefulness in identifying cognitive deficits and developing individualized treatment plans. The findings in this article will have significant implications on the clinical practice of neuropsychology in TBI patients, highlighting the importance of neuropsychological assessment in optimizing the management of this population. The need for increased awareness of neuropsychology among health care professionals, especially in the acute hospital setting, is growing along with the increase in diagnosis of TBI and its complications. Adequate understanding of the complex interplay between cognitive, emotional, and behavioral factors in TBI can inform the development of new interventions and treatment strategies, making it equally as important for patients and their families., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: In this research we evaluated molecular mechanism of effect of metformin in radio sensitivity of breast cancer cells., Methods: This research was done in cellular and molecular research center of Qazvin university of Medical science in 1399 to 1401. Studied samples were two breast cancer cell lines (MCF-7 and MDA-MB-231) they are derived from primary and secondary tumors resected from a single patient. We exposed them to cumulative 50 Gy radiation and constructed radio resistant cell lines. Then resistant cell lines were treated with 50µm of metformin. Our studied groups were resistant cells treated and un treated with metformin. Then, the expression rate of miR-21-5p and SESN1 gene in resistant and control cells was checked by Quantitative Real-time PCR(qRTPCR). After the cell lines were treated with different concentrations of metformin at different intervals, the rate of cell proliferation and cell death was checked by CCK-8 assay and flow cytometry. The Western blot method was also used to confirm the expression of some genes., Results: Our results showed that the expression of miR-21-5p was upregulated in radiation-resistant cancer cells (1.8±0.65) (P<0.0001) MCF-7 cell line and (1.6±0.42)(P<0.001) MBA-MD-231 cell line, while the expression of SESN1 was down regulated (0.46±0.12) (P<0.0001) MCF-7 cell line and (0.42±0.22) (P<0.001) MBA-MD-231 cell line. Metformin enhanced the radio sensitivity of breast cancer cells in a dose and time-dependent manner. Also, metformin treatment decreased the expression of miR-21-5p (0.47±0.32) (P<0.0001) MCF-7 Cell line and (0.45±0.21)(P<0.001) MBA-MD-231 cell line and increased the expression of SESN1 (1.65±0.72)(P<0.0001)MCF-7 cell line and (1.73±0.52)(P<0.0001) MBA-MD-231 cell line. The function of metformin was reversed by miR-21-5p inhibitors or the transfection of SESN1 overexpressing plasmids., Conclusion: In conclusion, based on this research results, metformin enhanced the radio sensitivity of breast cancer cells via modulating  the expression of miR-21-5p and SESN1.

This study aims to evaluate the role of preoperative vitamin D supplementation before coronary artery bypass grafting (CABG) surgery in preventing postoperative atrial fibrillation (POAF) in vitamin D deficient or insufficient patients. Three randomized controlled trials (RCTs) comprising 448 subjects were selected after a detailed search was conducted on PubMed, Cochrane CENTRAL, Scopus, and Embase in December 2022. Analysis was run using RevMan (version 5.4.1; Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). The analysis collected risk ratio (RR) and 95% confidence interval (CI) data from the relevant studies, which were then pooled using a random effects model. A significance level of less than 0.05 (p<0.05) was considered significant. Our analysis showed that compared with the standard of care, preoperative vitamin D supplementation in vitamin D deficient and insufficient patients effectively reduced POAF after CABG surgery (RR=0.6, 95% CI=0.4-0.9, P=0.01). There was no significant difference in the duration of hospitalization between the vitamin D supplementation group compared with the control following CABG (mean difference -0.85, 95% CI -2.13 to 0.43, P = 0.19). This meta-analysis shows that preoperative vitamin D supplementation in vitamin D deficient and insufficient patients undergoing CABG can reduce the rate of POAF. As POAF is associated with many complications, providing vitamin D supplementation to individuals with a vitamin D deficiency undergoing CABG can improve long-term cardiovascular outcomes following surgery., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ansari et al.)

Aims/introduction: Limited studies have identified risk factors linked to the progression of diabetic peripheral neuropathy (DPN) in type 2 diabetes. This study examined the association of risk factors with change in neuropathy measures over 2 years., Materials and Methods: Participants with type 2 diabetes (n = 78) and controls (n = 26) underwent assessment of clinical and metabolic parameters and neuropathy using corneal confocal microscopy (CCM), vibration perception threshold (VPT), and the DN4 questionnaire at baseline and 2 year follow-up., Results: Participants with type 2 diabetes had a lower corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) (P ≤ 0.0001) and a higher VPT (P ≤ 0.01) compared with controls. Over 2 years, despite a modest reduction in HbA1c (P ≤ 0.001), body weight (P ≤ 0.05), and LDL (P ≤ 0.05) the prevalence of DPN (P = 0.28) and painful DPN (P = 0.21) did not change, but there was a significant further reduction in CNBD (P ≤ 0.0001) and CNFL (P ≤ 0.05). CNFD, CNBD, and CNFL decreased significantly in physically inactive subjects (P < 0.05-0.0001), whilst there was no change in CNFD (P = 0.07) or CNFL (P = 0.85) in physically active subjects. Furthermore, there was no change in CNFD (P = 0.82), CNBD (P = 0.08), or CNFL (P = 0.66) in patients treated with glucose lowering medication associated with weight loss, whilst CNBD (P = 0.001) decreased in patients on glucose lowering medication associated with weight gain., Conclusions: In participants with type 2 diabetes, despite a modest improvement in HbA1c, body weight, and LDL there was a progressive loss of corneal nerve fibers; except in those who were physically active or on glucose lowering medication associated with weight loss., (© 2022 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Strengthening exercises are recommended for managing persisting upper limb (UL) weakness following a stroke. Yet, strengthening exercises often lead to variable gains because of their generic nature. For this randomized controlled trial (RCT), we aimed to determine whether tailoring strengthening exercises using a biomarker of corticospinal integrity, as reflected in the amplitude of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS), could optimize training effects in the affected UL. A secondary aim was to determine whether applying anodal transcranial direct current stimulation (tDCS) could enhance exercise-induced training effects. For this multisite RCT, 90 adults at the chronic stage after stroke (>6 months) were recruited. Before training, participants underwent TMS to detect the presence of MEPs in the affected hand. The MEP amplitude was used to stratify participants into three training groups: (1) low-intensity, MEP <50 μV, (2) moderate-intensity, 50 μV < MEP < 120 μV, and (3) high-intensity, MEP>120 μV. Each group trained at a specific intensity based on the one-repetition maximum (1 RM): low-intensity, 35-50% 1RM; moderate-intensity, 50-65% 1RM; high-intensity, 70-85% 1RM. The strength training targeted the affected UL and was delivered 3X/week for four consecutive weeks. In each training group, participants were randomly assigned to receive either real or sham anodal tDCS (2 mA, 20 min) over the primary motor area of the affected hemisphere. Pre-/post-intervention, participants underwent a clinical evaluation of their UL to evaluate motor impairments (Fugl-Meyer Assessment), manual dexterity (Box and Blocks test) and grip strength. Post-intervention, all groups exhibited similar gains in terms of reduced impairments, improved dexterity, and grip strength, which was confirmed by multivariate and univariate analyses. However, no effect of interaction was found for tDCS or training group, indicating that tDCS had no significant impact on outcomes post-intervention. Collectively, these results indicate that adjusting training intensity based on the size of MEPs in the affected extremity provides a useful approach to optimize responses to strengthening exercises in chronic stroke survivors. Also, the lack of add-on effects of tDCS applied to the lesioned hemisphere on exercise-induced improvements in the affected UL raises questions about the relevance of combining such interventions in stroke., Clinical Trial Registry Number: NCT02915185. https://www.clinicaltrials.gov/ct2/show/NCT02915185., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Palimeris, Ansari, Remaud, Tremblay, Corriveau, Boudrias and Milot.)

Introduction: COVID-19 infection in pregnancy ranges from asymptomatic infection to severe disease. However, the maternal and pregnancy outcomes are primarily favorable. Acute Respiratory Illness (ARI) score is a Visual Triage Checklist for Acute Respiratory symptoms created by the ministry of health of Saudi Arabia 12 to screen the patient for acute respiratory infection with MERS-CoV. It has been used during the COVID-19 pandemic to identify suspected cases and place patients in isolation precautions if the score is≥ 4., Method: This study is a cross-sectional study of all pregnant women who tested positive for COVID-19 in four medical centers located in four different cities in Saudi Arabia. The study period was from 1/3/2020 until 31/10/2020. Outcomes investigated were the prevalence of COVID infection in pregnant women at the time of delivery. Rate of asymptomatic disease, different maternal and pregnancy outcomes. Women were divided into symptomatic and asymptomatic groups according to the ARI score. The two groups were compared in maternal, perinatal, and neonatal outcomes. Furthermore, the cohort was divided according to maternal age into two groups: women of advanced maternal age ≥ 35 years and younger. The two groups were compared in maternal, perinatal, and neonatal outcomes RESULTS: During the study period, 9573 women gave birth at KAMCs, and 402 pregnant women were identified as COVID positive. Out of all COVID-positive women, only 394 women gave birth at KAMCs. The screening for COVID infection differed between the centers, but the testing was the same by the Nasopharyngeal polymerase chain reaction (PCR) swab. In Riyadh, screening was based on ARI scoring at the beginning of the pandemic. Then, it became universal. In Jeddah, the screening was based on ARI scoring. Any woman who scored four or more was labeled as suspected, and she was tested. Finally, in Madinah and Dammam, the screening was universal throughout the study. The prevalence of COVID-19 infection among women who gave birth at KAMCs was 4.2% (402/9573). (CI 3.8-4.6%). At the time of diagnosis, most women (62%) were asymptomatic. The most common symptoms were cough and shortness of breath. Twenty-two women (5.5%) had Pneumonia, and five women (1.3%) needed admission to Intensive care units (ICU). One woman died due to respiratory failure. When pregnancy outcomes were compared between symptomatic and asymptomatic women, pregnancy in symptomatic women was more likely to be complicated by Abortion (6 versus 2% p-value 0.00), fetal death (3 versus 1.3%), and cesarean delivery (30.8 versus 22.4%, p-value 0.001). COVID-positive pregnant women of advanced maternal age (AMA) were more likely to be symptomatic, have Abortion (5 versus 1%, p-value 0.01), and have Preterm delivery (17 versus 11% p-value 0.01) than younger women. In addition, neonatal death was more common in AMA COVID-positive women than younger (4 versus 0%), regardless of COVID-related symptoms., Conclusion: Most of the COVID-infected pregnant women are asymptomatic. Therefore, the ARI scoring system does not help to triage patients. Symptomatic women, especially those older than 35, tend to have a higher maternal and pregnancy complication rate., Competing Interests: Conflict of interest None., (Copyright © 2022. Published by Elsevier Ltd.)

Early diagnosis of breast cancer is an important component of breast cancer therapy. A variety of diagnostic platforms can provide valuable information regarding breast cancer patients, including image-based diagnostic techniques. However, breast abnormalities are not always easy to identify. Mammography, ultrasound, and thermography are some of the technologies developed to detect breast cancer. Using image processing and artificial intelligence techniques, the computer enables radiologists to identify chest problems more accurately. The purpose of this article was to review various approaches to detecting breast cancer using artificial intelligence and image processing. The authors present an innovative approach for identifying breast cancer using machine learning methods. Compared to current approaches, such as CNN, our particle swarm optimized wavelet neural network (PSOWNN) method appears to be relatively superior. The use of machine learning methods is clearly beneficial in terms of improved performance, efficiency, and quality of images, which are crucial to the most innovative medical applications. According to a comparison of the process's 905 images to those of other illnesses, 98.6% of the disorders are correctly identified. In summary, PSOWNNs, therefore, have a specificity of 98.8%. Furthermore, PSOWNNs have a precision of 98.6%, which means that, despite the high number of women diagnosed with breast cancer, only 830 (95.2%) are diagnosed. In other words, 95.2% of images are correctly classified. PSOWNNs are more accurate than other machine learning algorithms, SVM, KNN, and CNN., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Ashkan Nomani et al.)

The present review aimed to evaluate the impact of diabetes mellitus on dental implant failure rates and marginal bone loss (MBL). An electronic search was undertaken in three databases, plus a manual search of journals. Meta-analyses were performed as well as meta-regressions in order to verify how the odds ratio (OR) and MBL were associated with follow-up time. The review included 89 publications. Altogether, there were 5510 and 62,780 implants placed in diabetic and non-diabetic patients, respectively. Pairwise meta-analysis showed that implants in diabetic patients had a higher failure risk in comparison to non-diabetic patients (OR 1.777, p < 0.001). Implant failures were more likely to occur in type 1 diabetes patients than in type 2 (OR 4.477, p = 0.032). The difference in implant failure between the groups was statistically significant in the maxilla but not in the mandible. The MBL mean difference (MD) between the groups was 0.776 mm (p = 0.027), with an estimated increase of 0.032 mm in the MBL MD between groups for every additional month of follow-up (p < 0.001). There was an estimated decrease of 0.007 in OR for every additional month of follow-up (p = 0.048). In conclusion, implants in diabetic patients showed a 77.7% higher risk of failure than in non-diabetic patients.

Objective: To report on neurophysiological outcomes derived from transcranial magnetic stimulation (TMS) following autologous mesenchymal stem cells (aMSCs) therapy in patients with multiple sclerosis (MS)., Methods: 20 adults with confirmed MS were recruited to participate in a phase II randomized control trial to assess the safety and potential benefits of aMSCs infusion. At Week 0, patients were randomly assigned to receive either aMSCs (n = 9) or a placebo infusion (n = 11). At Week 24, the placebo group received the aMSCs infusion. Blind assessments were performed at Weeks 0, 24 and 48. Outcomes consisted of TMS measures of corticomotor excitability and motor conduction along with measures of motor impairments and disability., Results: Post-infusion, no change was detected in measures of corticomotor excitability or measures of intra- or interhemispheric inhibition. The latency of motor evoked potentials and central motor conduction time were significantly prolonged. These changes in motor conduction were associated with declines in hand dexterity post-infusion., Conclusion: Clinical and neurophysiological measures showed no improvement following aMSCs therapy in this cohort of MS patients., Significance: Although promising, stem cell therapy remains elusive regarding its benefits in influencing disease activity in MS patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Primary central nervous system lymphoma (PCNSL) is infrequent and often poses diagnostic conundrums due to its protean manifestations. We present the case of a South Asian young man presenting with raised intracranial pressure and a lymphocytic cerebrospinal fluid (CSF) with pronounced hypoglycorrhachia. Progression of the neuro-ophthalmic signs while on early stages of antitubercular treatment led to additional investigations that produced a final diagnosis of primary leptomeningeal lymphoma. Treatment with chemoimmunotherapy (methotrexate, cytarabine, thiotepa and rituximab (MATRix)) achieved full radiological remission followed by successful autologous transplant. This case highlights the difficulties and diagnostic dilemmas when PCNSL presents as a chronic meningeal infiltrative process. While contextually this CSF is most often indicative of central nervous system tuberculosis and justifies empirical treatment initiation alone, it is essential to include differential diagnoses in the investigation work-up, which also carry poor prognosis without timely treatment. High suspicion, multidisciplinary collaboration and appropriate CSF analysis were the key for a correct diagnosis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Superacids have been the source of much spectacular chemistry but very little interesting physics despite the fact that the states of cations formed by transfer of the superacid proton to molecular bases can approach that of the cations in free space. Indeed, some of the very strongest acids, such as HPF 6 and HAlCl 4 , have no independent existence due to lack of screening of the bare proton self-energy: their acidities can only be assessed by study of the conjugate bases. Here we show that, by allowing the protons of transient HAlCl 4 and HAlBr 4 to relocate on pentafluoropyridine, PFP (a very weak base that is stable to superacids), we can create glass forming protic ionic liquids (PILs) that are themselves superacids but, being free of superacid vapors, are of benign character. At T g , conductivities exceed "good" ionic liquid values by 9 decades, so must be superprotonic. Anomalous Walden plots confirm superprotonicity.

Background: Orthostatic hypotension is an excessive fall in blood pressure (BP) while standing and is the result of a decrease in cardiac output or defective or inadequate vasoconstrictor mechanisms. Fludrocortisone is a mineralocorticoid that increases blood volume and blood pressure. Fludrocortisone is considered the first- or second-line pharmacological therapy for orthostatic hypotension alongside mechanical and positional measures such as increasing fluid and salt intake and venous compression methods. However, there has been no Cochrane Review of the benefits and harms of this drug for this condition., Objectives: To identify and evaluate the benefits and harms of fludrocortisone for orthostatic hypotension., Search Methods: We searched the following databases on 11 November 2019: Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL. We also searched trials registries., Selection Criteria: We included all studies evaluating the benefits and harms of fludrocortisone compared to placebo, another drug for orthostatic hypotension, or studies without comparators, including randomized controlled trials (RCTs), quasi-RCTs and observational studies. We included studies in people with orthostatic hypotension due to a chronic peripheral neuropathy, a central autonomic neuropathy, or autonomic failure from other causes, but not medication-induced orthostatic hypotension or orthostatic hypotension from acute volume depletion or blood loss., Data Collection and Analysis: We used Cochrane methodological procedures for most of the review. We developed and used a tool to prioritize observational studies that offered the best available evidence where there are gaps in the evidence from RCTs. We assessed the certainty of evidence for fludrocortisone versus placebo using GRADE., Main Results: We included 13 studies of 513 participants, including three cross-over RCTs and 10 observational studies (three cohort studies, six case series and one case-control study). The included RCTs were small (total of 28 participants in RCTs), short term (two to three weeks), only examined fludrocortisone for orthostatic hypotension in people with two conditions (diabetes and Parkinson disease), and had variable risk of bias (two had unclear risk of bias and one had low risk of bias). Heterogeneity in participant populations, comparators and outcome assessment methods prevented meta-analyses of the RCTs. We found very low-certainty evidence about the effects of fludrocortisone versus placebo on drop in BP in people with diabetes (-26 mmHg versus -39 mmHg systolic; -7 mmHg versus -11 mmHg diastolic; 1 cross-over study, 6 participants). For people with Parkinson disease, we found very-low certainty evidence about the effects of fludrocortisone on drop in BP compared to pyridostigmine (-14 mmHg versus -22.1 mmHg diastolic; P = 0.036; 1 cross-over study, 9 participants) and domperidone (no change after treatment in either group; 1 cross-over study, 13 participants). For orthostatic symptoms, we found very low-certainty evidence for fludrocortisone versus placebo in people with diabetes (4 out of 5 analyzed participants had improvements in orthostatic symptoms, 1 cross-over study, 6 participants), for fludrocortisone versus pyridostigmine in people with Parkinson disease (orthostatic symptoms unchanged; 1 cross-over study, 9 participants) or fludrocortisone versus domperidone (improvement to 6 for both interventions on the Composite Autonomic Symptom Scale-Orthostatic Domain (COMPASS-OD); 1 cross-over study, 13 participants). Evidence on adverse events was also very low-certainty in both populations, but indicated side effects were minimal. Observational studies filled some gaps in evidence by examining the effects in larger groups of participants, with more diverse conditions, over longer periods of time. One cohort study (341 people studied retrospectively) found fludrocortisone may not be harmful in the long term for familial dysautonomia. However, it is unclear if this translates to long-term improvements in BP drop or a meaningful improvement in orthostatic symptoms., Authors' Conclusions: The evidence is very uncertain about the effects of fludrocortisone on blood pressure, orthostatic symptoms or adverse events in people with orthostatic hypotension and diabetes or Parkinson disease. There is a lack of information on long-term treatment and treatment of orthostatic hypotension in other disease states. There is a need for standardized reporting of outcomes and for standardization of measurements of blood pressure in orthostatic hypotension., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

A 32-year-old doctor, who has a medical history of primary Raynaud's disease and previous scotomas, presented to eye clinic with sudden onset blurring of vision (infero-nasally) with no other associated symptoms. The patient had good visual acuity bilaterally (6/6) and no anterior chamber activity or conjunctival hyperaemia. Findings consistent with a nerve fibre layer infarct were noted in the right eye, with unremarkable examination of the left eye. Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) images were obtained, which showed an area of capillary shut down in keeping with a nerve fibre layer lesion. Previous literature pertaining to similar symptoms is sparse with symptoms such as migraines, epilepsy and visual loss being stated. This case provides further evidence of Raynaud's associated retinal artery spasm, with complete resolution at 4 weeks. We also demonstrate the accessibility of OCT and more importantly OCTA for investigation of sudden onset visual deficit., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

A 56-year-old paramedic was admitted to hospital and treated for severe pneumonia. Shortly after initiating antibiotic treatment (including moxifloxacin), he developed bilaterally painful eyes and was diagnosed with bilateral acute anterior uveitis (AAU). Three years later, he was referred to the ophthalmology clinic with bilateral iris transillumination suggesting iris atrophy and limited pupillary dilation, indicating iris sphincter muscle paralysis. AAU typically presents unilaterally. An onset of bilateral AAU is unusual and warrants investigation for underlying systemic cause. The fluoroquinolone moxifloxacin has been reported in a limited number of cases as a causative agent of bilateral AAU and iris atrophy. This case provides additional supporting evidence that moxifloxacin may cause degradation of collagen and iris muscle in the eye, as well as elsewhere in the body, such as in blood vessels. Additionally, we present novel anterior segment ocular imaging (using optical coherence tomography) demonstrating the ability to detect iris atrophy using non-invasive imaging., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)