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Background: Among 547 patients receiving maribavir or valganciclovir for first-episode cytomegalovirus infection after hematopoietic cell transplant, the treatment response rate was 69.6% and 77.4% respectively. Development of maribavir and ganciclovir resistance was compared after receiving either drug., Methods: Viral mutations conferring drug resistance were analyzed in plasma DNA extracts at baseline and post-treatment., Results: Prior antiviral drug exposure was limited, with only 2 instances of baseline drug resistance detected. An equal number (n=241) received valganciclovir or maribavir for at least 21 days (median 55-56 days). Among them, drug resistance mutations were detected in 24 (10%) maribavir recipients at 35-125 days (median 56) after starting therapy, including in 12 of 14 who experienced a viral load rebound while on therapy. Ganciclovir resistance mutations developed in 6 (2.5%) valganciclovir recipients at 66-110 days (median 90). One maribavir recipient developed a novel UL97 gene mutation (P-loop substitution G343A) that conferred strong maribavir and ganciclovir resistance in vitro. Viral clearance was confirmed in 17 (74%) of 23 patients with emergent maribavir resistance after re-treatment with an alternative CMV antiviral drug., Conclusion: After 3-8 weeks of therapy, maribavir resistance emerged earlier and more frequently than ganciclovir resistance but was usually treatable using alternative therapy., Clinical Trials Registration: NCT02927067 (AURORA)., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Hepatitis E virus (HEV) is an emerging zoonotic pathogen that exhibits great host diversity. The primary means of transmission of the virus in low- and middle-income countries is contaminated water, often due to a lack of access to proper sanitation, which leads to faecal contamination of water sources. Environmental surveillance is an important tool that can be used to monitor virus circulation and as an early warning system for outbreaks. This study was conducted to determine the prevalence and genetic diversity of HEV in wastewater, surface water (rivers and standpipe/ablution water), and effluent from a piggery in South Africa. A total of 536 water samples were screened for HEV using real-time reverse transcription-polymerase chain reaction. Overall, 21.8% (117/536) of the wastewater, river, and ablution water samples tested positive for HEV, whereas 74.4% (29/39) of the samples from the piggery tested positive. Genotyping revealed sequences belonging to HEV genotypes 3 (98%, 53/54) and 4 (2%, 1/54), with subtypes 3c, 3f, and 4b being identified., (© 2024. The Author(s).)

The uptake of wastewater-based epidemiology (WBE) for SARS-CoV-2 as a complementary tool for monitoring population-level epidemiological features of the COVID-19 pandemic in low-and-middle-income countries (LMICs) is low. We report on the findings from the South African SARS-CoV-2 WBE surveillance network and make recommendations regarding the implementation of WBE in LMICs. Eight laboratories quantified influent wastewater collected from 87 wastewater treatment plants in all nine South African provinces from 01 June 2021 to 31 May 2022 inclusive, during the 3rd and 4th waves of COVID-19. Correlation and regression analyses between wastewater levels of SARS-CoV-2 and district laboratory-confirmed caseloads were conducted. The sensitivity and specificity of novel 'rules' based on WBE data to predict an epidemic wave were determined. Amongst 2158 wastewater samples, 543/648 (85 %) samples taken during a wave tested positive for SARS-CoV-2 compared with 842 positive tests from 1512 (55 %) samples taken during the interwave period. Overall, the regression-co-efficient was 0,66 (95 % confidence interval = 0,6-0,72, R 2  = 0.59), ranging from 0.14 to 0.87 by testing laboratory. Early warning of the 4th wave of SARS-CoV-2 in Gauteng Province in November-December 2021 was demonstrated. A 50 % increase in log copies of SARS-CoV-2 compared with a rolling mean over the previous five weeks was the most sensitive predictive rule (58 %) to predict a new wave. Our findings support investment in WBE for SARS-CoV-2 surveillance in LMICs as an early warning tool. Standardising test methodology is necessary due to varying correlation strengths across laboratories and redundancy across testing plants. A sentinel site model can be used for surveillance networks without affecting WBE finding for decision-making. Further research is needed to identify optimal test frequency and the need for normalisation to population size to identify predictive and interpretive rules to support early warning and public health action., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

The SARS-CoV-2 pandemic highlighted the need for novel tools to promote health equity. There has been a historical legacy around the location and allocation of public facilities (such as health care) focused on efficiency, which is not attainable in rural, low-density, United States areas. Differences in the spread of the disease and outcomes of infections have been observed between urban and rural populations throughout the COVID-19 pandemic. The purpose of this article was to review rural health disparities related to the SARS-CoV-2 pandemic while using evidence to support wastewater surveillance as a potentially innovative tool to address these disparities more widely. The successful implementation of wastewater surveillance in resource-limited settings in South Africa demonstrates the ability to monitor disease in underserved areas. A better surveillance model of disease detection among rural residents will overcome issues around the interactions of a disease and social determinants of health. Wastewater surveillance can be used to promote health equity, particularly in rural and resource-limited areas, and has the potential to identify future global outbreaks of endemic and pandemic viruses., 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., (© 2023 Elsevier Ltd. All rights reserved.)

Current workflows for colocalization analysis in fluorescence microscopic imaging introduce significant bias in terms of the user's choice of region of interest (ROI). In this work, we introduce an automatic, unbiased structured detection method for correlated region detection between two random processes observed on a common domain. We argue that although intuitive, using the maximum log-likelihood statistic directly suffers from potential bias and substantially reduced power. Therefore, we introduce a simple size-based normalization to overcome this problem. We show that scanning using the proposed statistic leads to optimal correlated region detection over a large collection of structured correlation detection problems.

A 21-year-old, usually fit and well man, presented with a 10-year history of intermittent, paroxysmal pain and temperature sensitivity to his right thumb. He felt this was associated with a subungual lesion present on the same digit. He was diagnosed as having a glomus tumour and was referred to the hand surgeons for surgical excision., (2015 BMJ Publishing Group Ltd.)

We have used the whole cell patch clamp technique to investigate the action of pentobarbitone on the nicotinic channels of bovine chromaffin cells. Application of agonists induced an inward current associated with a large increase in current noise. The noise could be fitted by Lorentzian functions with time constants of 17 +/- 2 ms for 10 microM acetylcholine and 10 +/- 1 ms for 10 microM carbachol. The single channel conductance estimated from the current variance was about 25 pS in each case. Pentobarbitone decreased the time constants in a concentration-dependent fashion, but the unit conductances were unaffected. Single channel events were recorded in chromaffin cells held under voltage clamp. Pentobarbitone did not reduce the amplitude of channel openings or the probability of channel opening but reduced the mean channel open time. This reduction was sufficient to account for the decrease in inward current produced by pentobarbitone.

A study of the forces generated by the intrinsic muscles of the index finger and coordinating muscles of the hand found that the intrinsic muscles of the index finger contributed combined forces equivalent to approximately 80% of those generated by the flexor profundus and superficialis, and to 73% of the moment for the motion of metacarpopalangeal flexion with simultaneous interphalangeal joint extension. No current tendon transfer operation can correct this deficit, though several supply sufficient force at the metacarpophalangeal joint to counterbalance the extrinsic extensors.

In deciding on suitable tendon transfers to replace denervated muscle-tendon units, important considerations are the strength and effectiveness of possible substitutes. A method is presented by which the strength of the wrist extensor muscles and their moment arms can be determined. The method can be applied to other muscles at other joints. It involves the use of a force transducer which measures the combined forces of the three wrist extensors in an isometric contraction. This moment for wrist extension, measured in the living intact arm, is the same as the sum of the moments of the three wrist extensor muscles. The contribution of each muscle to the total moment is calculated from ratios that have been developed from a quantitative study of moment arms and muscle masses in sixteen cadaver limbs. It is suggested that the ratio of one moment arm to another is fairly constant from subject to subject, and that muscle masses also have sufficiently similar ratios to each other to serve as the basis for practical estimations by the surgeon. Thus the surgeon needs only one or two direct measurements of moments externally and only one or two skeletal measurements on any living subject to be able to estimate the effectiveness of a number of muscles on the basis of cadaver studies such as this, and to project the behavior of a muscle after it has been transferred to a position where it will have new moment arms.