Non-pharmaceutical interventions to reduce COVID-19 transmission in the UK: a rapid mapping review and interactive evidence gap map.

BACKGROUND: Non-pharmaceutical interventions (NPIs) were crucial in the response to the COVID-19 pandemic, although uncertainties about their effectiveness remain. This work aimed to better understand the evidence generated during the pandemic on the effectiveness of NPIs implemented in the UK. METHODS: We conducted a rapid mapping review (search date: 1 March 2023) to identify primary studies reporting on the effectiveness of NPIs to reduce COVID-19 transmission. Included studies were displayed in an interactive evidence gap map. RESULTS: After removal of duplicates, 11 752 records were screened. Of these, 151 were included, including 100 modelling studies but only 2 randomized controlled trials and 10 longitudinal observational studies.Most studies reported on NPIs to identify and isolate those who are or may become infectious, and on NPIs to reduce the number of contacts. There was an evidence gap for hand and respiratory hygiene, ventilation and cleaning. CONCLUSIONS: Our findings show that despite the large number of studies published, there is still a lack of robust evaluations of the NPIs implemented in the UK. There is a need to build evaluation into the design and implementation of public health interventions and policies from the start of any future pandemic or other public health emergency.

Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III.

Analysis of patients with inherited hypokalaemic alkalosis resulting from salt-wasting has proved fertile ground for identification of essential elements of renal salt homeostasis and blood-pressure regulation. We now demonstrate linkage of this phenotype to a segment of chromosome 1 containing the gene encoding a renal chloride channel, CLCNKB. Examination of this gene reveals loss-of-function mutations that impair renal chloride reabsorption in the thick ascending limb of Henle's loop. Mutations in seventeen kindreds have been identified, and they include large deletions and nonsense and missense mutations. Some of the deletions are shown to have arisen by unequal crossing over between CLCNKB and the nearby related gene, CLCNKA. Patients who harbour CLCNKB mutations are characterized by hypokalaemic alkalosis with salt-wasting, low blood pressure, normal magnesium and hyper- or normocalciuria; they define a distinct subset of patients with Bartter's syndrome in whom nephrocalcinosis is absent. These findings demonstrate the critical role of CLCNKB in renal salt reabsorption and blood-pressure homeostasis, and demonstrate the potential role of specific CLCNKB antagonists as diuretic antihypertensive agents.

Repression of RAD51 gene expression by E2F4/p130 complexes in hypoxia.

We and others have shown that the dysregulation of DNA repair pathways can contribute to the phenomenon of hypoxia-induced genetic instability within the tumor microenvironment. Several studies have revealed that the recombinational repair genes, RAD51 and BRCA1, and the DNA mismatch repair genes, MLH1 and MSH2, are decreased in expression in response to hypoxic stress, prompting interest in elucidating the mechanistic basis for these responses. Here we report that the downregulation of RAD51 by hypoxia is specifically mediated by repressive E2F4/p130 complexes that bind to a single E2F site in the proximal promoter of the gene. Intriguingly, this E2F site is conserved in the promoter of the BRCA1 gene, which is also regulated by a similar mechanism in hypoxia. Mechanistically, we have found that hypoxia induces substantial p130 dephosphorylation and nuclear accumulation, leading to the formation of E2F4/p130 complexes and increased occupancy of E2F4 and p130 at the RAD51 and BRCA1 promoters. These findings reveal a coordinated transcriptional program mediated by the formation of repressive E2F4/p130 complexes that represents an integral response to hypoxic stress. In addition, this co-regulation of key factors within the homology-dependent DNA repair pathway provides a further basis for understanding genetic instability in tumors and may guide the design of new therapeutic strategies for cancer.

Studies in potential filaricides. 6. Synthesis of 3,8-disubstituted 1,3,8-triazabicyclo(4.4.0)decan-2-ones and -thiones.

1,3,8-Triazabicyclo[4.4.0]decan-2-ones and -thiones varying substituents at positions 3 and 8 have been synthesized. When tested in cotton rats for their antifilarial activity against Litomosoides carinii, some of the compounds showed moderate microfilaricidal activity.

Evaluation of a HSV specific monoclonal antibody reagent for laboratory diagnosis of herpes simplex virus infection.

A new FITC-conjugated HSV specific monoclonal antibody reagent (Syva Co., Palo Alto, Ca) was evaluated for the confirmation of HSV clinical isolates. The reagent was also compared to type-specific monoclonal antibodies for the pre-CPE detection of HSV from clinical specimens in centrifugation culture and by direct examination of specimens smears by direct immunofluorescent antibody staining (DFA). HSV was isolated from 75 of 232 specimens (32%). All 75 isolates were confirmed with both the type-specific antibodies and the HSV-specific reagent. In centrifugation culture HSV was detected in 36 of 105 (34%) specimens. The HSV specific reagent detected all 36 specimens that were positive with the type-specific reagents. HSV infection was diagnosed by DFA in 31 of 50 (62%) specimen smears. The HSV-specific reagent detected all 31 positive specimens. This reagent confirmed and detected all HSV positive specimens that were positive by the type-specific monoclonal antibody reagents. The reagent contains monoclonal antibodies specific for both HSV1 and HSV2 in a single mixture, which produces a highly sensitive HSV FA staining reagent.

The extraosseous and intraosseous arterial anatomy of the adult elbow.

UNLABELLED: We investigated the extraosseous and intraosseous arterial anatomy of the human adult elbow. Twenty-two fresh adult cadaveric upper extremities were studied with a technique of combined India-ink and latex injection followed by chemical débridement. The intraosseous vascularity of twelve extremities was then evaluated with a rapid Spalteholz clearing technique. Our findings demonstrated consistent patterns of extraosseous and intraosseous vascular anatomy, which were organized into three vascular arcades: medial, lateral, and posterior. The medial arcade was formed by the superior and inferior ulnar collateral arteries and the posterior ulnar recurrent artery. The lateral arcade was formed by the radial and middle collateral, radial recurrent, and interosseous recurrent arteries. The posterior arcade was formed by the medial and lateral arcades and the middle collateral artery. The intraosseous circulation of the elbow, which was segmental in organization, appeared to be dependent on the local blood supply. The capitellum and the lateral aspect of the trochlea were supplied by posterior perforating vessels arising from the radial recurrent, radial collateral, and interosseous recurrent arteries. The medial aspect of the trochlea was supplied by a circumferential vascular ring originating from the inferior ulnar collateral artery. Watershed areas were apparent between the blood supplies to the medial and lateral aspects of the distal end of the humerus. The olecranon was richly supplied by vessels coursing along its medial aspect from the posterior ulnar recurrent artery and along its lateral aspect from the interosseous recurrent artery. The radial head had a dual extraosseous blood supply from a single branch of the radial recurrent artery, which supplied the head directly, and from additional vessels from both the radial and the interosseous recurrent artery, which penetrated the capsular insertion at the neck of the radius. CLINICAL RELEVANCE: Our findings demonstrate that arterial contributions to the intraosseous circulation of the elbow are more specific than previously appreciated. The intraosseous circulation of the elbow is derived mainly from perforating vessels that arise from neighboring extraosseous arteries. These perforating arteries may be damaged by trauma or by extensile dissection during reconstruction of the elbow. An understanding of the extraosseous and intraosseous circulation of the elbow may help to avoid iatrogenic injury to the intraosseous circulation.

Quantification of the radial torsion angle with computerized tomography in cadaver specimens.

Torsion of a long bone is the twist along its longitudinal axis; torsion of the radius is defined by the angle between the proximal and distal metaphyses in the transverse plane. Measurement of the radial torsion angle provides a means of detection and quantification of malrotation after a fracture. The purpose of the current study was to develop and standardize a technique for the measurement of torsion of the radius. Axial computerized tomographic images of thirty-nine pairs of dry cadaver specimens of normal radii, and an additional four pairs of radii with a unilateral deformity of the distal metaphysis that was consistent with a previous fracture, were studied and a measurement protocol was established. The radial torsion angle was measured by three independent observers on two separate occasions. Reproducibility of the technique was determined with use of the intraclass correlation coefficient to express both interobserver and intraobserver reliability. Consistency of measurements between observers and by the same observer was high, with intraclass correlation coefficients ranging from 0.87 to 0.94. The mean torsion angle for the eighty-two normal radii in the study was 32.6 degrees (95 per cent confidence interval of the mean, 30.3 to 34.9 degrees; range, 1.4 to 58.8 degrees). There were small variations in torsion angle between the two radii of each normal pair (mean side-to-side difference, 4.9 degrees; 95 per cent confidence interval of the mean, 3.5 to 6.3 degrees). The mean torsion angle of the four radii with a malunited fracture was 10.4 degrees (95 per cent confidence interval of the mean, 5.7 to 15.1 degrees), and the mean side-to-side difference in the pairs containing these radii was 24.1 degrees (95 per cent confidence interval of the mean, 8.5 to 39.6 degrees; p < 0.0001 compared with the normal radii).

Changes in interstitial pressure and cross-sectional area of the cubital tunnel and of the ulnar nerve with flexion of the elbow. An experimental study in human cadavera.

The purpose of this study was to determine the relationship between the ulnar nerve and the cubital tunnel during flexion of the elbow with use of magnetic resonance imaging and measurements of intraneural and extraneural interstitial pressure. Twenty specimens from human cadavera were studied with the elbow in positions of incremental flexion. With use of magnetic resonance imaging, cross-sectional images were made at each of three anatomical regions of the cubital tunnel: the medial epicondyle, deep to the cubital tunnel aponeurosis, and deep to the flexor carpi ulnaris muscle. The cross-sectional areas of the cubital tunnel and the ulnar nerve were calculated and compared for different positions of elbow flexion. Interstitial pressures were measured with use of ultrasonographic imaging to allow a minimally invasive method of placement of the pressure catheter, both within the cubital tunnel and four centimeters proximal to it, at 10-degree increments from 0 to 130 degrees of elbow flexion. As the elbow was moved from full extension to 135 degrees of flexion, the mean cross-sectional area of the three regions of the cubital tunnel decreased by 30, 39, and 41 per cent and the mean area of the ulnar nerve decreased by 33, 50, and 34 per cent. These changes were significant in all three regions of the cubital tunnel (p < 0.05). The greatest changes occurred in the region beneath the aponeurosis of the cubital tunnel with the elbow at 135 degrees of flexion. The mean intraneural pressure within the cubital tunnel was significantly higher than the mean extraneural pressure when the elbow was flexed 90, 100, 110, and 130 degrees (p < 0.05). With the elbow flexed 130 degrees, the mean intraneural pressure was 45 per cent higher than the mean extraneural pressure (p < 0.001). Similarly, with the elbow flexed 120 degrees or more, the mean intraneural pressure four centimeters proximal to the cubital tunnel was significantly higher than the mean extraneural pressure (p < 0.01). Relative to their lowest values, intraneural pressure increased at smaller angles of flexion than did extraneural pressure, both within the cubital tunnel and proximal to it. With the numbers available, we could not detect any significant difference in intraneural pressure measured, either at the level of the cubital tunnel or four centimeters proximal to it, after release of the aponeurotic roof of the cubital tunnel.

One-stop clinic for assessment of risk of chromosomal defects at 12 weeks of gestation.

Prenatal diagnosis of trisomy 21 requires an invasive test in women considered to be at high risk after screening. At present, there are four screening tests. For a 5% false-positive rate, the sensitivities are approximately 30% for maternal age alone, 60-70% for maternal age and second-trimester maternal serum biochemical testing, 75% for maternal age and first-trimester fetal nuchal translucency (NT) scanning, and 90% for maternal age with fetal NT and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11-14 weeks. This article examines the methodology of first-trimester screening and summarizes the results from all studies reporting on the implementation of this method.

Fetal nasal bone length in chromosomally normal and abnormal fetuses at 11-14 weeks of gestation.

OBJECTIVE: To determine the value of measuring fetal nasal bone length at 11-14 weeks of gestation in screening for chromosomal defects. METHODS: The fetal profile was examined and the nasal bone length was measured in 1092 fetuses immediately before chorionic villous sampling for karyotyping at 11-14 weeks of gestation. RESULTS: The median gestation was 12 (11-14) weeks. The fetal profile was successfully examined in all cases. The fetal karyotype was normal in 955 pregnancies and abnormal in 137, including 79 cases of trisomy 21. In the chromosomally normal group, the fetal nasal bone length increased significantly with crown-rump length (CRL) from a mean of 1.3 mm at a CRL of 45 mm to 2.1 mm at a CRL of 84 mm. In 54 of the 79 (68.4%) cases of trisomy 21, the nasal bone was absent. In the 25 cases with present nasal bone, the nasal bone length for the CRL was not significantly different from normal. Similarly, there were no significant differences from normal in the nasal bone length of fetuses with other chromosomal defects. CONCLUSIONS: At 11-14 weeks of gestation, the nasal bone length of chromosomally abnormal fetuses is not significantly different from normal.

Second-trimester sex hormone-binding globulin and subsequent development of pre-eclampsia.

OBJECTIVE: To investigate whether maternal plasma sex hormone-binding globulin (SHBG) concentrations are reduced in women who subsequently develop pre-eclampsia. METHODS: This was a cross-sectional study, carried out at antenatal clinics in seven hospitals in and around London. Healthy women underwent uterine artery Doppler velocimetry as a screening method for pre-eclampsia at 22-24 weeks of gestation. The first group (408 women) had normal uterine artery Doppler waveforms (mean uterine artery pulsatility index (PI) below 1.6). The second group (274 women) had increased impedance to flow in the uterine arteries (mean PI above the 95th centile, 1.6). Maternal plasma SHBG concentrations were measured retrospectively using a competitive chemiluminescent immunoassay. Pre-eclampsia was as defined by the International Society for the Study of Hypertension in Pregnancy. RESULTS: Plasma SHBG concentrations in the 80 (11.7%) women who subsequently developed pre-eclampsia were significantly lower than in the 585 (85.8%) women with normal pregnancy outcomes (median 336, range 142-674 nmol/l vs. median 336, range 142-674 nmol/l, p = 0.001). There was a strong correlation between SHBG concentrations and body mass index (r =-0.232246, p < 0.0001). There were no significant differences in maternal plasma SHBG concentrations in women with abnormal uterine artery Doppler (n = 274) compared with controls (n = 408) (median 324, range 101-635 nmol/l vs. median 336, range 142-674 nmol/l, p = 0.09). CONCLUSION: Maternal plasma SHBG concentrations are reduced in women who subsequently develop pre-eclampsia.

Injuries causing major loss of scalp.

Long hair worn by both sexes in a majority of the rural population of Punjab (India) increases the hazard of descalping injuries. Forty-six cases seen over a period of 10 years are reported. Agricultural machinery accounted for 83 percent of these injuries. Males were most commonly involved (63 percent), and 48 percent of the patients were minors. Nearly all cases reported had at least half the scalp avulsed, 56.5 percent being total scalp avulsions, with bare bone exposed in 48 percent of the total. The method of chiseling the outer portion of the exposed bone down to bleeding points and immediately applying a split-thickness skin graft is presented as the procedure of choice for wound closure. This reduced the average hospitalization period by 49 percent as compared with older methods. Follow-up of 67 percent of patients has revealed a surprising instability of the grafted skin, with an ultimate danger of malignant degeneration.

Extensive nodular sarcoidosis in the hand.

We report an atypical case of nodular sarcoidosis involving both hands. The pattern of extensive involvement of all digits with lesions extending into the pulp spaces has not been reported previously. The diagnosis of sarcoidosis should be considered even in patients presenting with clinically uncharacteristic manifestations.

Assessing outcome after hand surgery: the current state.

An overview of the current state of outcome measurement after hand surgery is presented. The paper focuses on the development, application and strengths and weaknesses of it also reviews the existing questionnaires and suggests recommendations for use in research or clinical practice.

The additive effects of smoking and hypertension. More reasons to help your patients kick the habit.

Although the link between cigarette smoking and its cardiovascular effects is well established, the mechanisms through which smoking raises blood pressure remain to be clarified. Possible mechanisms include nicotine-induced peripheral and central sympathetic nervous system stimulation, persisting levels of nicotine in blood because of incomplete metabolism, release of vasopressin, and chemoreceptor stimulation. Effects of nicotine on hemostasis, arterial rigidity, and vessel wall damage, together with detrimental effects on lipid metabolism, may contribute to an overall increased cardiovascular risk in smokers. Nonselective beta blockers are not as effective in smokers as they are in nonsmokers. Smoking cessation is a very important intervention in reducing cardiovascular risk in hypertensive patients. Physicians should counsel patients about smoking cessation at every visit. Use of the various smoking deterrents can help some patients quit.

The occult dorsal carpal ganglion: usefulness of magnetic resonance imaging and ultrasound in diagnosis.

Both magnetic resonance imaging and ultrasonography of the wrist have been advocated for the diagnosis of occult dorsal carpal ganglia. This clinical series compares the utility of the two techniques for confirming clinical suspicion of such occult ganglia. Four wrists in three patients with suspected occult dorsal ganglia were identified prospectively over a 12-month period. Each patient underwent imaging with both techniques on the same day. Subsequently, the wrist was operatively explored and the excised tissue was microscopically evaluated. All wrists in this series had positive magnetic resonance imaging and ultrasound findings, with operative and histologic confirmation of the diagnosis. No diagnostic advantage of one imaging study over the other was identified. With its lower cost and lack of contraindications, ultrasound may be the more suitable technique for establishing the diagnosis of occult dorsal carpal ganglion when clinical findings are inconclusive.

A novel approach to first-trimester screening for early pre-eclampsia combining serum PP-13 and Doppler ultrasound.

OBJECTIVE: To investigate the value of maternal serum placental protein 13 (PP-13) measurement and uterine artery Doppler during first-trimester screening in the prediction of early pre-eclampsia. METHODS: This was a nested case-control prospective study of pregnancies at 11 + 0 to 13 + 6 weeks of gestation. The pulsatility index (PI) of blood flow in the uterine arteries and the maternal serum concentration of PP-13 were measured in 10 women who went on to develop pre-eclampsia that necessitated delivery before 34 weeks, and in 423 unaffected women. Results were expressed as multiples of the gestation-specific median in controls (MoM). A logistic regression model was used to predict detection and false-positive rates. RESULTS: In the cases that developed pre-eclampsia requiring delivery before 34 weeks, compared with the unaffected pregnancies, the median uterine artery PI was higher (1.43 MoM) and the median serum PP-13 level was lower (0.07 MoM; P < 0.001, Wilcoxon rank sum test for both). Modeling predicted that for a 90% detection rate of pre-eclampsia requiring delivery before 34 weeks, the false-positive rate of screening by PP-13 was 12%, by uterine artery PI was 31% and by a combination of the two methods was 9%. A policy of contingency screening, whereby all women are screened by maternal serum PP-13 and only the 14% at highest risk are then screened by Doppler, achieved a detection rate of 90% with an overall false-positive rate of 6%. CONCLUSION: Effective screening for pre-eclampsia requiring delivery before 34 weeks can potentially be provided by assessment of a combination of maternal serum PP-13 and uterine artery Doppler in the first trimester of pregnancy.