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To determine whether classification systems improve patient-reported outcomes for people with low back pain (LBP).Systematic review with meta-analysis.The MEDLINE, Embase, CINAHL, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials databases were searched from inception to June 21, 2021. Reference lists of prior systematic reviews and included trials were screened.We included randomized trials comparing a classification system (eg, the McKenzie method or the STarT Back Tool) to any comparator. Studies evaluating participants with specific spinal conditions (eg, fractures or tumors) were excluded.Outcomes were patient-reported LBP intensity, leg pain intensity, and disability. We used the revised Cochrane Collaboration Risk of Bias Tool to assess risk of bias, and the Grading of Recommendations Assessment, Development and Evaluation approach to judge the certainty of evidence. We used random-effects meta-analysis, with the Hartung-Knapp-Sidik- Jonkman adjustment, to estimate the standardized mean difference (SMD; Hedges'Twenty-four trials assessing classification systems and 34 assessing subclasses were included. There was low certainty of a small effect at the end of intervention for LBP intensity (SMD, -0.31; 95% CI: -0.54, -0.07;For patient-reported pain intensity and disability, there is insufficient evidence supporting the use of classification systems over generalized interventions when managing LBP.

The discovery of compounds and proteins from plants has greatly contributed to modern medicine. Vernonia amygdalina Del. (Compositae) is used by humans and primates for a variety of conditions including parasitic infection. This paper describes the serendipitous discovery that V. amygdalina extract was able to bind to, and functionally inhibit, active TGFβ1. The binding agent was isolated and identified as chlorophyll a-b binding protein AB96. Given that active TGFβ1 contributes to the pathology of many infectious diseases, inhibiting these processes may explain some of the benefits associated with the ingestion of this species. This is the first plant-derived cytokine-neutralizing protein to be described and paves the way for further such discoveries.

The blood pressure response to exercise is exaggerated in type 2 diabetes mellitus (T2DM). However, the underlying mechanisms remain unclear. It is hypothesized that one mechanism mediating the potentiated cardiovascular response in T2DM is the sensitization of chemically sensitive afferent neurons by activation of metaboreceptors. To test this hypothesis, we examined transient receptor potential cation channel subfamily V member 1 (TRPV1)-induced cardiovascular responses in vivo and muscle afferent discharge ex vivo in T2DM rats. Additionally, TRPV1 and protein kinase C (PKC) protein levels in dorsal root ganglia (DRG) subserving skeletal muscle were assessed. For 14-16 weeks, Sprague-Dawley rats were given either a normal diet (control) or high fat diet in combination with a low dose (35 and 25 mg/kg) of streptozotocin (T2DM). Administration of capsaicin, TRPV1 agonist, in hindlimb evoked significantly greater increases in mean arterial pressure and renal sympathetic neve activity in decerebrated T2DM than control. In a muscle-nerve preparation, the discharge to capsaicin exposure in group IV afferents isolated from T2DM was likewise significantly augmented at a magnitude that was proportional to glucose concentration. Moreover, the discharge to capsaicin was potentiated by acute exposure of group IV afferents to a high glucose environment. T2DM showed significantly increased phospholyrated-TRPV1 and −PKCα levels in DRG neurons as compared with control. These findings suggest that group IV muscle afferents are sensitized by PKC-induced TRPV1 overactivity in early-stage T2DM with hyperglycemia and, thereby, may contribute to the potentiated circulatory response to TRPV1 activation in the disease.

Background The strength and size of core muscles, including the abdominal muscles, are crucial to proper function in most activities. Therefore, it is important to reliably assess these characteristics. Our primary objective was to determine if the length, thickness and cross-sectional area of the transversus abdominis (TrA) can be visualized independently from the internal and external abdominal oblique muscles using extended field of view ultrasound imaging at rest and with contraction and to establish its intra- and inter-tester reliability. Methods Twenty-six individuals were recruited to participate in the study (20 F, 6 M), average age 24.0 years (SD 9.4), height 170.7 cm (SD 8.6) and weight 63.9 kg (SD 9.0). From this total number of participants, two groups of 16 randomly selected participants were assessed to determine intra- and inter-tester reliability respectively. Extended field of view ultrasound images were obtained at three vertebral levels during rest and contraction in the side lying position for both the right and left sides of the trunk. Results Excellent intra-tester and inter-tester reliability was seen (ICC range of 0.972 to 0.984). The overall average percent standard error of the measurement for all measurements and locations was approximately 4%. The overall average minimal difference for the thickness measurement for the resting and contraction conditions combined were as follows: intratester 0.056 (0.014) cm and intertester 0.054 (0.017) cm, for area intratester 0.287 (0.086) cm2 and intertester 0.289 (0.101) cm2 and for length intratester 0.519 (0.097) cm and intertester 0.507 (0.085) cm. Conclusions Extended field of view ultrasound imaging is an effective method of reliably capturing clear images of the TrA during rest and contraction. It provides an efficient mechanism for the analysis of muscle morphology by being able to measure the cross-sectional area, thickness, and length on one image. This methodology is recommended for studies investigating TrA function and training.

Purpose Acyclovir is most commonly used for treating ocular Herpes Keratitis, a leading cause of infectious blindness. However, emerging resistance to Acyclovir resulting from mutations in the thymidine kinase gene of Herpes Simplex Virus −1 (HSV-1), has prompted the need for new therapeutics directed against a different viral protein. One novel target is the HSV-1 Processivity Factor which is essential for tethering HSV-1 Polymerase to the viral genome to enable long-chain DNA synthesis. Methods A series of peptides, based on the crystal structure of the C-terminus of HSV-1 Polymerase, were constructed with hydrocarbon staples to retain their alpha-helical conformation. The stapled peptides were tested for blocking both HSV-1 DNA synthesis and infection. The most effective peptide was further optimized by replacing its negative N-terminus with two hydrophobic valine residues. This di-valine stapled peptide was tested for inhibiting HSV-1 infection of human primary corneal epithelial cells. Results The stapled peptides blocked HSV-1 DNA synthesis and HSV-1 infection. The unstapled control peptide had no inhibitory effects. Specificity of the stapled peptides was confirmed by their inabilities to block infection by an unrelated virus. Significantly, the optimized di-valine stapled peptide effectively blocked HSV-1 infection in human primary corneal epithelial cells with selectivity index of 11.6. Conclusions Hydrocarbon stapled peptides that simulate the α-helix from the C-terminus of HSV-1 DNA polymerase can specifically block DNA synthesis and infection of HSV-1 in human primary corneal epithelial cells. These stapled peptides provide a foundation for developing a topical therapeutic for treating human ocular Herpes Keratitis.

Patients with type 2 diabetes display an exaggerated pressor response to exercise. However, evidence supporting the association between the magnitude of the pressor response to exercise and insulin resistance-related factors including hemoglobin A1c (HbA1c) or homeostatic model assessment of insulin resistance (HOMA-IR) in nondiabetic subjects has remained sparse and inconclusive. Thus we investigated the relationship between cardiovascular responses to exercise and insulin resistance-related factors in nondiabetic healthy men (n = 23) and women (n = 22) above 60 yr old. We measured heart rate (HR) and blood pressure (BP) responses during: isometric handgrip (IHG) exercise of 30% maximal voluntary contraction, a period of skeletal muscle ischemia (SMI) induced by tourniqueting the arm after IHG, and rhythmic dynamic handgrip (DHG) exercise during SMI. Greater diastolic BP (DBP) responses to DHG with SMI was associated with male sex (r = 0.44, P = 0.02) and higher HbA1c (r = 0.33, P = 0.03), heart-ankle pulse wave velocity (haPWV) (r = 0.45, P < 0.01), and resting systolic BP (SBP) (r = 0.36, P = 0.02). HbA1c persisted as a significant determinant explaining the variance in the DBP response to DHG with SMI in multivariate models despite adjustment for sex, haPWV, and resting SBP. It was also determined that the DBP response to DHG with SMI in a group in which HOMA-IR was abnormal (Δ33 ± 3 mmHg) was significantly higher than that of groups in which HOMA-IR was at intermediate (Δ20 ± 4 mmHg) and normal (Δ23 ± 2 mmHg) levels. These data suggest that even in nondiabetic older adults, insulin resistance is related to an exaggerated pressor response to exercise especially when performed under ischemic conditions. NEW & NOTEWORTHY The diastolic blood pressure response to rhythmic dynamic handgrip exercise under ischemic conditions was demonstrated to be correlated with insulin resistance-related factors in nondiabetic older adults. This finding provides important insight to the prescription of exercise in this particular patient population as the blood pressure response to exercise, especially under ischemic conditions, could be exaggerated to nonsafe levels.

BACKGROUND Rapid access to blood products can be lifesaving for hemorrhaging patients, but placing blood components in easily accessible locations in the emergency department (ED) can lead to wasteful patterns of use. Education can lead to improvements in transfusion behavior, but such changes for the better are often short lived. METHODS To facilitate the early initiation of balanced resuscitation, an emergency blood refrigerator was placed in our ED in February 2015. Physician education to give blood components in a 1:1 plasma:red blood cell (RBC) unit ratio with the plasma given first was given repeatedly with short-term success. Finally, nurses were trained and empowered to strongly suggest that blood components be given in balanced ratios and that plasma be given first. Plasma:RBC unit ratios were compared in successive years with the chi-square test for trend. RESULTS A total of 1165 RBC units and 623 plasma units were issued from the ED emergency blood refrigerator over 5 years. Intensive physician education is documented at start, in late 2016 to early 2017, and again in early and late 2018. Ratios of components (U plasma/U RBCs) were 2015, 17%; 2016, 26%; 2017, 61%; 2018, 49%; and 2019, 91% (p

PURPOSE This study aimed to investigate if the Functional Movement Screen (FMS) total score, individual component test scores, or number of asymmetries can predict noncontact injury risk over three consecutive seasons of National Collegiate Athletic Association Division I football. METHODS Because football teams comprise individuals with vastly different physical characteristics and playing responsibilities, we divided the subjects into three homogeneous groups based on position (big, combo, and skill). Each FMS score was assessed with regard to the total team score and by individual position groups. For our injury analysis, we also controlled for exposure. Two hundred and eight National Collegiate Athletic Association Division I athletes participated over three consecutive seasons, yielding a total of 343 observations. RESULTS There was no significant relationship between total FMS score and likelihood of injury when analyzed by the total team or by position group. These findings were the same for all groups, for both the total number of injuries and injuries weighted by injury exposure. The only significant findings occurred when we considered individual test item scores to injury by position group. We only found a significant relationship in the expected direction with push-up stability in the combo group. CONCLUSIONS FMS was not a good predictor of noncontact injury.

Injury of the tooth pulp is excruciatingly painful and yet the receptors and neural circuit mechanisms that transmit this form of pain remain poorly defined in both the clinic and preclinical rodent models. Easily quantifiable behavioral assessment in the mouse orofacial area remains a major bottleneck in uncovering molecular mechanisms that govern inflammatory pain in the tooth. In this study we sought to address this problem using the Mouse Grimace Scale and a novel approach to the application of mechanical Von Frey hair stimuli. We use a dental pulp injury model that exposes the pulp to the outside environment, a procedure we have previously shown produces inflammation. Using RNAscope technology, we demonstrate an upregulation of genes that contribute to the pain state in the trigeminal ganglia of injured mice. We found that mice with dental pulp injury have greater Mouse Grimace Scores than sham within 24 hours of injury, suggestive of spontaneous pain. We developed a scoring system of mouse refusal to determine thresholds for mechanical stimulation of the face with Von Frey filaments. This method revealed that mice with a unilateral dental injury develop bilateral mechanical allodynia that is delayed relative to the onset of spontaneous pain. This work demonstrates that tooth pain can be quantified in freely behaving mice using approaches common for other types of pain assessment. Harnessing these assays in the orofacial area during gene manipulation should assist in uncovering mechanisms for tooth pulp inflammatory pain and other forms of trigeminal pain.

Purpose This study aimed to determine if brief psychosocial/behavioral therapy directed to reduce poststroke depression would decrease fatigue and improve sleep-wake disturbance. Design A preplanned secondary data analysis from a completed clinical trial was conducted. Methods One hundred participants received usual care, in-person intervention, or telephone intervention. Depression, fatigue, and sleep-wake disturbance were measured at entry, 8 weeks, 21 weeks, and 12 months following the intervention. Findings Fatigue (within: p = .042, between: p = .394), sleep disturbance (within: p = .024, between: p = .102), and wake disturbance (within: p = .004, between: p = .508) decreased over the 12 months in the intervention groups, but not in the control group. This difference was clinically meaningful for wake disturbance and approached the clinically important difference for fatigue. Conclusions/clinical relevance Reduction in wake disturbance was consistent with clinically meaningful difference standards for patient-reported outcomes, warranting further research in larger samples.

Background Consumer engagement is a requirement of high quality clinical guidelines. Developing strategies to engage consumers and incorporate the perspectives of individuals with or at risk of pressure ulcers/injuries and their informal caregivers was one priority in the recent update of the EPUAP/NPIAP/PPPIA's Prevention and Treatment of Pressure Ulcers/Injuries: Clinical Practice Guideline. Aims The aims were to determine the goals of individuals and caregivers for pressure ulcer/injury care, priorities for pressure ulcer/injury education and biggest problems related to pressure ulcers/injuries. Methods An online, anonymous, international 10-item survey, accessible in nine languages was provided to individuals and their caregivers from April to October 2018. Descriptive statistics were used for quantitative data and a thematic analysis approach was used to analyse qualitative data. Results There were 1233 individuals from 27 countries who completed the survey. Overall, individuals and caregivers had similar goals of care. Reducing the size of pressure ulcer/injury was selected more often as a care goal than complete healing. Individuals, compared to caregivers, considered managing pain more important. Qualitative data analysis identified five themes including knowledge, attitudes, and skills; risk factors for pressure ulcer/injury; accessing pressure ulcer/injury care; quality of life for patients and caregivers; and the pressure ulcer/injury. Conclusions The consumer survey provided consumer engagement and perspective that was incorporated into guideline development, including consideration during evaluation of the relevance and acceptability of recommendations, and assignment of recommendation strength ratings.

Introduction The most common cancers in the UK are keratinocyte cancers (KCs): the combined term for basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (cSCCs). Registration of KC is challenging due to high numbers and multiplicity of tumours per person. Methods We provide an updated report on the descriptive epidemiology of trends in KC incidence for the resident populations of UK countries (England, Northern Ireland, Scotland and Wales) using population‐based cancer registry and pathology report data, 2013–18. Results Substantial increases in cSCC incidence in England, Scotland and Northern Ireland can be detected for the period of 2013–18, and the incidence of cSCC also increased in Wales from 2016 to 2018. In contrast, however, the pattern of annual change in the incidence of BCC across the nations differs. In England, the incidence of BCC declined slightly from 2016 to 2018, however, the overall trend across 2013–18 is not statistically significant. In Scotland, the incidence of BCC shows some variability, declining in 2017 before increasing in 2018, and the overall trend across 2013–18 was also not statistically significant. In Northern Ireland, the incidence of BCC increased significantly over the study period, and in Wales, the incidence of BCC increased from 2016 to 2018. One in five people will develop non‐melanoma skin cancers (NMSC) in their lifetime in England. This estimate is much higher than the lifetime risk of melanoma (1 in 36 males and 1 in 47 females born after 1960 in the UK), which further highlights the burden of the disease and importance of early prevention strategies. Conclusions We highlight how common these tumours are by publishing the first ever lifetime incidence of NMSC. Additionally, the first time reporting of the age standardised incidence of KC in Wales further confirms the scale of the disease burden posed by these cancers in the UK. With approximately one in five people developing NMSC in their lifetime, optimisation of skin cancer prevention, management and research are essential.

Skin cancer is the commonest cancer in the UK. Skin cancer referrals via the two-week wait (urgent suspected cancer) pathway outnumber any other suspected malignancy.1, 2 The commonest skin cancers are keratinocyte cancers (KCs) which represents Basal Cell Carcinomas (BCC) and Cutaneous Squamous Cell Carcinomas (cSCC). Accurate KC incidence reporting is crucial for healthcare planning.

In Cameroon, in 2019, tuberculosis (TB) treatment coverage was estimated at 53%, indicating that almost half of all people sick with TB were not diagnosed or linked to care. To inform strategies to improve access to TB services, we conducted an evaluation of the alignment between patient-initiated care-seeking behavior and spatial and institutional allocation of TB services. Data sources included the Cameroon Demographic and Health Survey (2018), the Health Facility List (2017), and routinely collected TB surveillance data. Data visualization was performed in Tableau and QGIS. The pathway analysis showed that only an estimated 9% of people attended a health facility providing TB services at initial care-seeking, with access varying from

Background The identification of endogenous signals that lead to microglial activation is a key step in understanding neuroinflammatory cascades. As ATP release accompanies mechanical strain to neural tissue, and as the P2X7 receptor for ATP is expressed on microglial cells, we examined the morphological and molecular consequences of P2X7 receptor stimulation in vivo and in vitro and investigated the contribution of the P2X7 receptor in a model of increased intraocular pressure (IOP). Methods In vivo experiments involved intravitreal injections and both transient and sustained elevation of IOP. In vitro experiments were performed on isolated mouse retinal and brain microglial cells. Morphological changes were quantified in vivo using Sholl analysis. Expression of mRNA for M1- and M2-like genes was determined with qPCR. The luciferin/luciferase assay quantified retinal ATP release while fura-2 indicated cytoplasmic calcium. Microglial migration was monitored with a Boyden chamber. Results Sholl analysis of Iba1-stained cells showed retraction of microglial ramifications 1 day after injection of P2X7 receptor agonist BzATP into mouse retinae. Mean branch length of ramifications also decreased, while cell body size and expression of Nos2, Tnfa, Arg1, and Chil3 mRNA increased. BzATP induced similar morphological changes in ex vivo tissue isolated from Cx3CR1+/GFP mice, suggesting recruitment of external cells was unnecessary. Immunohistochemistry suggested primary microglial cultures expressed the P2X7 receptor, while functional expression was demonstrated with Ca2+ elevation by BzATP and block by specific antagonist A839977. BzATP induced process retraction and cell body enlargement within minutes in isolated microglial cells and increased Nos2 and Arg1. While ATP increased microglial migration, this required the P2Y12 receptor and not P2X7 receptor. Transient elevation of IOP led to microglial process retraction, cell body enlargement, and gene upregulation paralleling changes observed with BzATP injection, in addition to retinal ATP release. Pressure-dependent changes were reduced in P2X7−/− mice. Death of retinal ganglion cells accompanied increased IOP in C57Bl/6J, but not P2X7−/− mice, and neuronal loss showed some association with microglial activation. Conclusions P2X7 receptor stimulation induced rapid morphological activation of microglial cells, including process retraction and cell body enlargement, and upregulation of markers linked to both M1- and M2-type activation. Parallel responses accompanied IOP elevation, suggesting ATP release and P2X7 receptor stimulation influence the early microglial response to increased pressure.

Mitochondrial dysfunction and excessive inflammatory responses are both sufficient to induce pathology in age-dependent neurodegenerations. However, emerging evidence indicates crosstalk between damaged mitochondrial and inflammatory signaling can exacerbate issues in chronic neurodegenerations. This review discusses evidence for the interaction between mitochondrial damage and inflammation, with a focus on glaucomatous neurodegeneration, and proposes that positive feedback resulting from this crosstalk drives pathology. Mitochondrial dysfunction exacerbates inflammatory signaling in multiple ways. Damaged mitochondrial DNA is a damage-associated molecular pattern, which activates the NLRP3 inflammasome; priming and activation of the NLRP3 inflammasome, and the resulting liberation of IL-1β and IL-18 via the gasdermin D pore, is a major pathway to enhance inflammatory responses. The rise in reactive oxygen species induced by mitochondrial damage also activates inflammatory pathways, while blockage of Complex enzymes is sufficient to increase inflammatory signaling. Impaired mitophagy contributes to inflammation as the inability to turnover mitochondria in a timely manner increases levels of ROS and damaged mtDNA, with the latter likely to stimulate the cGAS-STING pathway to increase interferon signaling. Mitochondrial associated ER membrane contacts and the mitochondria-associated adaptor molecule MAVS can activate NLRP3 inflammasome signaling. In addition to dysfunctional mitochondria increasing inflammation, the corollary also occurs, with inflammation reducing mitochondrial function and ATP production; the resulting downward spiral accelerates degeneration. Evidence from several preclinical models including the DBA/2J mouse, microbead injection and transient elevation of IOP, in addition to patient data, implicates both mitochondrial damage and inflammation in glaucomatous neurodegeneration. The pressure-dependent hypoxia and the resulting metabolic vulnerability is associated with mitochondrial damage and IL-1β release. Links between mitochondrial dysfunction and inflammation can occur in retinal ganglion cells, microglia cells and astrocytes. In summary, crosstalk between damaged mitochondria and increased inflammatory signaling enhances pathology in glaucomatous neurodegeneration, with implications for other complex age-dependent neurodegenerations like Alzheimer’s and Parkinson’s disease.

Patients with diabetes display heightened blood pressure response to exercise but the underlying mechanism are remains to be elucidated. There is no direct evidence that insulin resistance (hyperinsulinemia or hyperglycemia) impact neural cardiovascular control during exercise. We propose a novel paradigm in which hyperinsulinemia or hyperglycemia significantly influence neural regulatory pathways controlling the circulation during exercise in diabetes.

KEY POINTS Insulin is known to activate the sympathetic nervous system centrally. A mechanical stimulus to tissues activates the sympathetic nervous system via thin fibre afferents. Evidence suggests that insulin modulates putative mechanosensitive channels in the dorsal root ganglion neurons of these afferents. In the present study, we report the novel finding that insulin augments the mechanical responsiveness of thin fibre afferents not only at dorsal root ganglion, but also at muscle tissue levels. Our data suggest that sympathoexcitation is mediated via the insulin-induced mechanical sensitization peripherally. The present study proposes a novel physiological role of insulin in the regulation of mechanical sensitivity in somatosensory thin fibre afferents. ABSTRACT Insulin activates the sympathetic nervous system, although the mechanism underlying insulin-induced sympathoexcitation remains to be determined. A mechanical stimulus to tissues such as skin and/or skeletal muscle, no matter whether the stimulation is noxious or not, activates the sympathetic nervous system via thin fibre afferents. Evidence suggests that insulin modulates putative mechanosensitive channels in the dorsal root ganglion (DRG) neurons of these afferents. Accordingly, we investigated whether insulin augments whole-cell current responses to mechanical stimuli in small DRG neurons of normal healthy mice. We performed whole-cell patch clamp recordings using cultured DRG neurons and observed mechanically-activated (MA) currents induced by mechanical stimuli applied to the cell surface. Local application of vehicle solution did not change MA currents or mechanical threshold in cultured DRG neurons. Insulin (500 mU mL-1 ) significantly augmented the amplitude of MA currents (P

PURPOSE This study investigated the relationship between blood flow restriction (BFR) cuff pressure and blood flow at rest and during exercise, with the aim of determining if lower cuff pressures will provide an ischemic stimulus comparable to higher pressures. METHODS The relationship between blood flow and cuff pressure at rest was determined by measuring blood flow (Doppler Ultrasound) through the superficial femoral artery (SFA) in 23 adults across a range of pressures (0%-100% Arterial Occlusion Pressure at rest [rAOP]). The interplay between cuff pressure, blood flow and exercise was assessed by determining AOP at rest and during plantar flexion exercise (eAOP) and subsequently measuring the blood flow response to plantar flexion exercise with BFR cuff pressure set to either 40% rAOP or 40% eAOP. RESULTS At rest, a nonlinear relationship between cuff pressure and blood flow through the SFA exhibited a plateau at moderate pressures, with nonsignificant differences in blood flow (~9%, P = 1.0) appearing between pressures ranging from 40% to 80% rAOP. While eAOP was greater than rAOP (229 ± 1.5 mm Hg vs 202 ± 1.5 mm Hg, P < 0.01), blood flow during plantar flexion exercise did not significantly differ (P = 0.49) when applying 40% rAOP or 40% eAOP. CONCLUSIONS Blood flow through the SFA exhibits a nonlinear relationship with cuff pressure, such that cuff pressures in the range of 40% to 80% rAOP reduce blood flow to approximately the same degree. The BFR interventions opting for lower (e.g., 40% AOP), more comfortable pressures will likely provide an ischemic stimulus comparable to that of higher (80% AOP), less-comfortable pressures.

Objective This study was conducted to measure and to determine differences in tissue depth in the upper back for two prone positions and to stratify the results by body composition and sex of the patient. In addition, muscle thickness changes with positioning were assessed. This information is important for clinicians who dry needle in the thorax area, cognizant of the dangers of inadvertently piercing the pleura or lung tissue. Design Descriptive cross-sectional. Setting Health and Human Performance laboratory at a university campus. Participants Sample of convenience of 60 college-aged subjects, 20 subjects in three body composition groups. Main outcome measures Distances from skin to lung tissue, skin to ribs and muscle thickness were measured and compared between two prone positions. Results There was a significant increase in depth to the lung tissue (0.7 cm, 95% confidence interval 0.4–1.0 cm) when using a bolster under the shoulder. There were also differences in depths between body composition classifications and between sexes, but not between sides. The average thickness of all muscles increased significantly by up to 0.4 cm (95% confidence interval 0.3–0.5) when the shoulder was positioned in retraction. Conclusions Positioning, body constitution and sex of the patient change tissue depth significantly and should be considered when dry needling. This change is largely attributed to a modification in muscle thickness.

Retinal injuries and diseases are major causes of human disability involving vision impairment by the progressive and permanent loss of retinal neurons. During development, assembly of this tissue entails a successive and overlapping, signal-regulated engagement of complex events that include proliferation of progenitors, neurogenesis, cell death, neurochemical differentiation and synaptogenesis. During retinal damage, several of these events are re-activated with both protective and detrimental consequences. Purines and pyrimidines, along with their metabolites are emerging as important molecules regulating both retinal development and the tissue’s responses to damage. The present review provides an overview of the purinergic signaling in the developing and injured retina. Recent findings on the presence of vesicular and channel-mediated ATP release by retinal and retinal pigment epithelial cells, adenosine synthesis and release, expression of receptors and intracellular signaling pathways activated by purinergic signaling in retinal cells are reported. The pathways by which purinergic receptors modulate retinal cell proliferation, migration and death of retinal cells during development and injury are summarized. The contribution of nucleotides to the self-repair of the injured zebrafish retina is also discussed.

The cardiovascular responses to exercise are potentiated in patients with type 2 diabetes mellitus (T2DM). However, the underlying mechanisms causing this abnormality remain unknown. Central command (CC) and the exercise pressor reflex (EPR) are known to contribute significantly to cardiovascular control during exercise. Thus these neural signals are viable candidates for the generation of the abnormal circulatory regulation in this disease. We hypothesized that augmentations in CC as well as EPR function contribute to the heightened cardiovascular responses during exercise in T2DM. To test this hypothesis, changes in mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) in response to electrical stimulation of mesencephalic locomotor region (MLR), a putative component of the central command pathway, and activation of the EPR, evoked by electrically induced hindlimb muscle contraction, were examined in decerebrate animals. Sprague-Dawley rats were given either a normal diet (control) or a high-fat diet (14–16 wk) in combination with two low doses (35 mg/kg week 1, 25 mg/kg week 2) of streptozotocin (T2DM). The changes in MAP and RSNA responses to MLR stimulation were significantly greater in T2DM compared with control (2,739 ± 123 vs. 1,298 ± 371 mmHg/s, 6,326 ± 1,621 vs. 1,390 ± 277%/s, respectively, P < 0.05). Similarly, pressor and sympathetic responses to activation of the EPR in diabetic animals were significantly augmented compared with control animals (436 ± 74 vs. 134 ± 44 mmHg/s, 645 ± 135 vs. 139 ± 65%/s, respectively, P < 0.05). These findings provide the first evidence that CC and the EPR may generate the exaggerated rise in sympathetic activity and blood pressure during exercise in T2DM.

Purpose In hospital-based studies, patients intubated by physicians while in an inclined position compared to supine position had a higher rate of first pass success and lower rate of peri-intubation complications. We evaluated the impact of patient positioning on prehospital endotracheal intubation in an EMS system with rapid sequence induction capability. We hypothesized that patients in the inclined position would have a higher first-pass success rate. Methods Prehospital endotracheal intubation cases performed by paramedics between 2012 and 2017 were prospectively collected in airway registries maintained by a metropolitan EMS system. We included all adult (age ≥ 18 years) non-traumatic, non-arrest patients who received any attempt at intubation. Patients were categorized according to initial positioning: supine or inclined. The primary outcome measure was first pass success with secondary outcomes of laryngoscopic view and challenges to intubation. Results Of the 13,353 patients with endotracheal intubation attempted by paramedics during the study period, 4879 were included for analysis. Of these, 1924 (39.4%) were intubated in the inclined position. First pass success was 86.3% among the inclined group versus 82.5% for the supine group (difference 3.8%, 95% CI: 1.5%–6.1%). First attempt laryngeal grade I view was 62.9% in the inclined group versus 57.1% for the supine group (difference 5.8%, 2.0–9.6). Challenges to intubation were more frequent in the supine group (42.3% versus 38.8%, difference 3.5%, 0.6–6.3). Conclusion Inclined positioning was associated with a better grade view and higher rate of first pass success. The technique should be considered as a viable approach for prehospital airway management.

___Key messages___ The Commission recommends five priority investments to achieve a tuberculosis-free world within a generation. These investments are designed to fulfil the mandate of the UN High Level Meeting on tuberculosis. In addition, they answer the question of how countries with high-burden tuberculosis and their development partners should target their future investments to ensure that ending tuberculosis is achievable. __Invest first to ensure that high quality rapid diagnostics and treatment are provided to all individuals receiving care for tuberculosis, wherever they seek care__ This priority includes rapid drug susceptibility testing and second-line treatment for resistant forms of tuberculosis. Achieving universal, high-quality person-centred and family-centred care—including sustained improvement in the performance of private sector providers—usually should be the top policy and budget priority. __Reach people and populations at high risk for tuberculosis (such as household and other close contacts of people with tuberculosis, and people with HIV) and bring them into care__ Active case-finding and treatment in high-risk populations demands adequate resources to reach and care for these populations. At the same time, reaching certain high-risk populations, such as people co-infected with tuberculosis and HIV, for tuberculosis preventive therapy is essential to achieve epidemiologic control. Once high-risk populations have access to affordable, high-quality diagnostic, treatment and preventive services, invest in identifying tuberculosis cases in the general population, primarily by strengthening the capacity to deliver health services and move toward universal health coverage. __Increase investment to accelerate tuberculosis research and development and bring new diagnostics, therapeutic strategies, and vaccines to clinical practice to quickly end the pandemic__ Strong advocacy with science ministries and research-oriented pharmaceutical companies is crucial, including ministries and companies in middle-income countries, to highlight the importance of investing in new tools. Financing the early uptake of new products will provide important confidence signals to product developers. __Make investment in tuberculosis programmes a shared responsibility, increasing development assistance for tuberculosis according to the financial needs of individual low-income and middle-income countries__ As countries successfully mobilise more domestic resources towards tuberculosis programmes, external assistance to middle-income countries should address the following priorities: reduce the spread of drug-resistant tuberculosis in all affected low-income and middle-income countries; facilitate market-shaping activities to enable access to high quality drugs and diagnostics for high-burden countries; and finance tuberculosis research and development, including product development as well as population, policy, and implementation research that will provide lessons and international sharing of best practices. __Hold countries and key stakeholders accountable for progress made towards ending tuberculosis__ Accountability entails establishing independent, multisectoral processes, such as national tuberculosis report cards, to ensure that all stakeholders carry out their responsibilities to contribute to ending the pandemic. Accountability mechanisms should not only assess progress, but also guarantee that Heads of Governments, national tuberculosis programmes, and even regional and site-level clinics, as well as key non-governmental organisations, take the necessary corrective actions to remove obstacles to ending tuberculosis.

Background: Inorganic phosphate (Pi) is used extensively as a preservative and a flavor enhancer in the Western diet. Physical inactivity, a common feature of Western societies, is associated with increased cardiovascular morbidity and mortality. It is unknown whether dietary Pi excess contributes to exercise intolerance and physical inactivity. Methods: To determine an association between Pi excess and physical activity in humans, we assessed the relationship between serum Pi and actigraphy-determined physical activity level, as well as left ventricular function by cardiac magnetic resonance imaging, in DHS-2 (Dallas Heart Study phase 2) participants after adjusting for relevant variables. To determine direct effects of dietary Pi on exercise capacity, oxygen uptake, serum nonesterified fatty acid, and glucose were measured during exercise treadmill test in C57/BL6 mice fed either a high-Pi (2%) or normal-Pi (0.6%) diet for 12 weeks. To determine the direct effect of Pi on muscle metabolism and expression of genes involved in fatty acid metabolism, additional studies in differentiated C2C12 myotubes were conducted after subjecting to media containing 1 to 3 mmol/L Pi (pH 7.0) to simulate in vivo phosphate conditions. Results: In participants of the DHS-2 (n=1603), higher serum Pi was independently associated with reduced time spent in moderate to vigorous physical activity ( P =0.01) and increased sedentary time ( P =0.004). There was no association between serum Pi and left ventricular ejection fraction or volumes. In animal studies, compared with the control diet, consumption of high-Pi diet for 12 weeks did not alter body weight or left ventricular function but reduced maximal oxygen uptake, treadmill duration, spontaneous locomotor activity, fat oxidation, and fatty acid levels and led to downregulation of genes involved in fatty acid synthesis, release, and oxidation, including Fabp4 , Hsl , Fasn , and Pparγ , in muscle. Similar results were recapitulated in vitro by incubating C2C12 myotubes with high-Pi media. Conclusions: Our data demonstrate a detrimental effect of dietary Pi excess on skeletal muscle fatty acid metabolism and exercise capacity that is independent of obesity and cardiac contractile function. Dietary Pi may represent a novel and modifiable target to reduce physical inactivity associated with the Western diet.

Rationale: Early antibiotics improve outcomes for patients with sepsis. Factors influencing antibiotic timing in emergency department (ED) sepsis remain unclear.Objectives: Determine the relationsh...

BACKGROUND: Drug resistance poses a major barrier to global control of TB – a leading infectious cause of death. Depression and stigma occur commonly among people with TB. However, the relationship between drug-resistant forms of TB, depression and stigma are not well understood.OBJECTIVE: To compare depression, stigma and health-related quality of life (HRQoL), among people with drug-susceptible TB (DS-TB) and multidrug-resistant TB (MDR-TB).METHODS: A cross-sectional study of people treated for DS-TB and MDR-TB in four provinces of Vietnam. The survey included a stigma scale (Vietnamese Tuberculosis Stigma Scale), depression scale (9-item Patient Health Questionnaire) and HRQoL scale (Functional Assessment of Chronic Illness Therapy – Tuberculosis). Differences between the two populations were compared using linear regression.RESULTS: Eighty-one people with DS-TB and 315 people with MDR-TB participated in the study. People with MDR-TB had a higher prevalence of depression than those with DS-TB (difference 17.8%, χ2 8.64). The mean depression and stigma scores were higher for people with MDR-TB than those with DS-TB (adjusted difference [AD] 8.6 and 7.6 respectively). People with MDR-TB reported lower HRQoL than those with DS-TB (AD –23.8).CONCLUSION: Depression and stigma are common among people with TB in Vietnam. Strategies to prevent and treat depressive symptoms and stigma in people with TB are critical to a holistic, patient-centred approach to care.

Numerous studies have demonstrated that sympathetic nervous system overactivation during exercise in hypertensive rodents and humans is due, in part, to an exaggerated reflex response known as the exercise pressor reflex. Our prior studies have implicated a key role of mineralocorticoid receptor activation in mediating an augmented exercise pressor reflex in spontaneously hypertensive rats, which is mitigated by blockade with eplerenone. However, the effect of eplerenone on exercise pressor reflex has not been assessed in human hypertension. Accordingly, the authors performed a randomized crossover study to compare the effects of eplerenone to another antihypertensive drug from a different class amlodipine on sympathetic nerve activity (SNA) in 14 patients with uncomplicated hypertension. The authors found that amlodipine unexpectedly augmented the increase in SNA during the second minute of isometric handgrip, which persisted into the post‐exercise circulatory arrest period (∆ SNA, from rest of 15 ± 2 vs. 9 ± 2 vs. 10 ± 2 bursts/min, amlodipine vs. baseline vs. eplerenone, respectively, p

Statement of purpose Community violence exposure is known to have adverse effects on children’s long-term mental health. We aimed to examine the association between episodes of neighborhood gun violence and subsequent acute mental health-related pediatric emergency department (ED) utilization. Methods/Approach This location-based neighborhood study included children living in Philadelphia, PA who presented to a children’s hospital ED from 1/1/2014–12/31/2018. We included children in the study if they had one or more ED visits within 7, 30, and 60 days of a neighborhood shooting and lived within 660 feet (2–3 city blocks) of where the incident occurred. Mental health-related presentations were identified using ED chief complaint data. We used multivariable logistic regression to compare odds of mental health-related ED utilization before and after neighborhood shootings. Results There were 4,217 episodes of gun violence in the study area from 2014–2018, and 54,465 children living near a shooting had one or more ED visits in the 60 days before or after this shooting. Most of these children were Black (84.5%) and Medicaid-insured (78.2%). After adjusting for age, race, ethnicity, insurance status, and zip code, children residing within 660 feet of an episode of gun violence had greater odds of mental health-related ED presentations in the subsequent 7 days (aOR 1.49, 95% CI, 1.08–2.04), 30 days (aOR 1.25, 95%CI 1.05–1.48), and 60 days (adjusted odds ratio (aOR 1.14, 95%CI 1.01–1.29). In stratified analyses, this effect was strongest for Black children (7-day aOR 1.52, 95%CI 1.08–2.14) and children ages 11–19 (7-day aOR 1.60, 95%CI 1.08–2.39). Conclusions and Significance Neighborhood gun violence has immediate adverse effects on children’s mental health. Recognizing the potentially triggering event and mitigating these health impacts will require both community-based support for children exposed to violence, and trauma- informed approaches during and after ED visits.

Microglial cells regulate neural homeostasis by coordinating both immune responses and clearance of debris, and the P2X7 receptor for extracellular ATP plays a central role in both functions. The P2X7 receptor is primarily known in microglial cells for its immune signaling and NLRP3 inflammasome activation. However, the receptor also affects the clearance of extracellular and intracellular debris through modifications of lysosomal function, phagocytosis, and autophagy. In the absence of an agonist, the P2X7 receptor acts as a scavenger receptor to phagocytose material. Transient receptor stimulation induces autophagy and increases LC3-II levels, likely through calcium-dependent phosphorylation of AMPK, and activates microglia to an M1 or mixed M1/M2 state. We show an increased expression of Nos2 and Tnfa and a decreased expression of Chil3 (YM1) from primary cultures of brain microglia exposed to high levels of ATP. Sustained stimulation can reduce lysosomal function in microglia by increasing lysosomal pH and slowing autophagosome-lysosome fusion. P2X7 receptor stimulation can also cause lysosomal leakage, and the subsequent rise in cytoplasmic cathepsin B activates the NLRP3 inflammasome leading to caspase-1 cleavage and IL-1β maturation and release. Support for P2X7 receptor activation of the inflammasome following lysosomal leakage comes from data on primary microglia showing IL-1β release following receptor stimulation is inhibited by cathepsin B blocker CA-074. This pathway bridges endolysosomal and inflammatory roles and may provide a key mechanism for the increased inflammation found in age-dependent neurodegenerations characterized by excessive lysosomal accumulations. Regardless of whether the inflammasome is activated via this lysosomal leakage or the better-known K+-efflux pathway, the inflammatory impact of P2X7 receptor stimulation is balanced between the autophagic reduction of inflammasome components and their increase following P2X7-mediated priming. In summary, the P2X7 receptor modulates clearance of extracellular debris by microglial cells and mediates lysosomal damage that can activate the NLRP3 inflammasome. A better understanding of how the P2X7 receptor alters phagocytosis, lysosomal health, inflammation, and autophagy can lead to therapies that balance the inflammatory and clearance roles of microglial cells.

Introduction and Objectives The disease spectrum of COVID-19 ranges from mild viral illness to devastating lung injury that heralds the acute respiratory distress syndrome Different risk factors of adverse outcomes have been identified but prospectively stratified and externally validated studies of prognosis are lacking We set out to identify independent predictors of mortality and to develop and validate a clinically applicable risk prediction model of COVID-19 Methods 983 consecutive patients with COVID-19 were prospectively recruited over an 11-week period for an outcome of in-hospital death Multiple imputation was used to address randomly missing data 12 independent mortality predictors were identified by multivariate regression and internally validated by bootstrapping A prognostic score was constructed and validated in an external cohort (N=277) and assessed for predictive accuracy including goodness-of-fit by the Hosmer-Lemeshow test Results The median age of the derivation cohort was 70 (IQR: 53-83) Among non-survivors (29 9%;294/983), the highest odds ratios for death (with 95% confidence intervals) were age >70 (7 65;4 89-11 98;P30 (2 39;1 88-3 03;P

COVID-19 posed unprecedented challenges on healthcare systems globally especially on inpatient beds, oxygen and ventilatory support: Continuous positive airway pressure (CPAP), high flow nasal oxygen and invasive mechanical ventilation (IMV) West Herts NHS Trust, a secondary care provider for a population of 650,000 had 1200 admissions during the first wave (March to June) with a 30% mortality Ventilatory outcomes in 116 consecutive admissions were analysed to assess the utility of CPAP in a respiratory specialist ward versus ITU, and prompt versus delayed invasive mechanical ventilation (IMV) Respiratory support was provided in four pathways: CPAP in intensive care unit (ITU) (n=18), CPAP in respiratory ward setting (usually as ceiling of care, n=50), IMV after initial trial of CPAP (n=21) and IMV with no delay or interim CPAP (n=27) The demographics, comorbidities, functional status, severity of presentation and outcomes differed greatly between the ward group and all the ITU arms Within the ITU arms, patients were younger, had worse chest X-rays, higher CRP as well as had lower lymphocyte counts, PF (PaO2/FiO2) ratios and comorbidities Delayed intubation with a trial of CPAP was associated with significant mortality compared to prompt IMV All ventilatory outcomes were poor in patients over 80 years Mortality rate was significantly lower in prompt IMV, 37%, compared to 95% in those with a delayed intubation by a median of 6 days with a prior CPAP trial Median PF ratio on admission for patients with prompt IMV was 73 mmHg vs 115 mmHg in those with CPAP prior to IMV In summary, ward CPAP as ceiling of care for older patients and with comorbidities is safe and associated with a relatively similar mortality rate compared to ITU CPAP but must be reviewed regularly to ensure improvement on treatment Mortality is significant in those with lower PF ratios especially if IMV is delayed Whilst acknowledging the heavy burden on clinicians to rationalise treatment during times of limited resources, we believe that careful assessment of age, comorbidities (cardiac and frailty), PF ratios, CRP and a 24 hourly review should be undertaken to prevent delayed IMV in appropriate patients

An increasing number of studies have reported a deleterious role of inorganic phosphate (Pi) in promoting hypertension. Previously, we have shown high Pi diet-induced excessive pressor and sympathetic responses to muscle contraction in otherwise normal rats, which were primarily mediated by an overactive exercise pressor reflex (EPR), a reflex arising from contracting muscle. However, the mechanism underlying these abnormalities generated by excess Pi intake remains unclear. Dietary Pi is known to increase release of bone-derived fibroblast growth factor (FGF) 23 to regulate Pi homeostasis. Evidence suggests that FGF23 and FGF receptors (FGFRs) are also present in the central nervous system. The aim of this study was to determine the role of brain FGFRs in mediating augmented EPR activity induced by dietary Pi excess. Accordingly, we assessed cerebrospinal fluid FGF23 levels in Sprague-Dawley rats fed either a normal 0.6% Pi diet (NP) or a high 1.2% Pi diet (HP) for 12 weeks. To determine the role of central FGFRs in mediating the EPR, we measured mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) responses to hindlimb muscle contraction before and after intracerebroventricular (ICV) administration of either a selective FGFR4 inhibitor BLU9931 or a FGFR1/2/3 inhibitor AZD4547 in decerebrate NP and HP animals. Cerebrospinal fluid FGF23 levels were significantly higher in HP rats compared to NP rats (8.3±0.9 vs. 7.2±0.8 pM, P

Cytokine release from non-inflammatory cells is a key step in innate immunity, and agonists triggering cytokine release are central in coordinating responses. P2X7 receptor (P2X7R) stimulation by extracellular ATP is best known to active the NLRP3 inflammasome and release IL-1&beta, but stimulation also leads to release of other cytokines. As cytokine signaling by retinal pigmented epithelial (RPE) cells is implicated in retinal neurodegeneration, the role of P2X7R in release of cytokine IL-6 from RPE cells was investigated. P2X7R stimulation triggered IL-6 release from primary mouse RPE, human iPS-RPE and human ARPE-19 cells. IL-6 release was polarized, with predominant rise across apical membranes. IL-6 release was inhibited by P2X7R antagonists A438079, A839977, and AZ10606120, but not the NRTI lamivudine (3TC), P2X1R antagonist NF279, or P2Y1R antagonist MRS2179. P2X7R-mediated IL-6 release required extracellular Ca2+ and was blocked by Ca2+ chelator BAPTA. IL-6 release and Ca2+ elevation occurred rapidly, consistent with vesicular IL-6 staining in unstimulated cells. P2X7R stimulation did not trigger IL-1&beta, release in these unprimed cells. P2X7R-mediated IL-6 release was enhanced in RPE cells from the ABCA4&minus, /&minus, mouse model of retinal degeneration. In summary, P2X7R stimulation triggers rapid Ca2+-dependent IL-6 release across the apical membrane of RPE cells.

The discovery of compounds and proteins from plants has greatly contributed to modern medicine, especially in malaria where both quinine and artemisinin have been the cornerstone of therapeutics. Here we describe the first known plant-derived cytokine binding agent. Chlorophyll a-b binding protein AB96, present to varying levels in the leaves of all chlorophyll-containing plants, binds to active TGFβ1. Active TGFβ1 contributes to the pathology of many infectious and neoplastic diseases and therefore, by inhibiting these processes, chlorophyll a-b binding protein opens up new approaches with therapeutic potential.

Mitchell, UH, Owen, PJ, Rantalainen, T, and Belavý, DL. Increased joint mobility is associated with impaired transversus abdominis contraction. J Strength Cond Res 36(9): 2472-2478, 2022-Increased joint mobility is a risk factor for joint injury, but muscle function may be able to compensate for it. Current evidence suggests reduced force production capacity in people with hypermobility. However, little is known about the lumbar spine. The purpose of this cross-sectional study was to assess whether there was a link between joint mobility and transverse abdominis and multifidus muscles contraction, muscles ascribed a core-stability role. Using a modified quantitative version of the Beighton scale (BOM score), we measured joint mobility of 30 middle-aged individuals without low back pain. These scores were correlated with magnetic resonance imaging-derived measures of transverse abdominis and multifidus muscle contraction during a spinal loading maneuver. The level of significance was set for p ≤ 0.05. The results showed greater joint mobility (a higher BOM score) correlated ( r = 0.468; p = 0.009) with reduced transversus abdominis (TrA) shortening during contraction (i.e., less muscle shortening in people with greater joint mobility). The trunk subdomain score exhibited a correlation of 0.354 with TrA length change, but this did not reach statistical significance ( p = 0.055). The subdomains of the BOM score did not correlate significantly with each other ( p ≥ 0.097). No association was seen between multifidus contraction and joint mobility. The results suggest that greater general joint mobility is associated with impaired contraction of the TrA muscle. This should be considered when coaching athletes or treating patients with (functional) spinal instability. The quantitative approach we developed to measure joint mobility could be used in the future studies of global flexibility.

Long‐term care facilities have been identified as a local epicenter of disease among populations vulnerable to coronavirus disease 2019 (COVID‐19). A skilled nursing facility in Washington State was the first major site of COVID‐19 infections in the United States. Many lessons were learned during the events surrounding this outbreak, including how to develop, and the importance of, a coordinated response between emergency medical services and local area hospitals. As these events came early in the U.S. pandemic, unfortunately, disease spread and mortality was high. However, these events also resulted in rapid mobilization of the regional response to the COVID‐19 pandemic. Understanding the events surrounding this outbreak demonstrate some of the challenges involved in responding to acute infectious illnesses within these unique environments and associated vulnerable populations.

Summary A measles outbreak in London is described, involving 34 cases across two hospitals and a local community across two countries. After a single introduction to hospital, spread propagated via unvaccinated retail shop workers to healthcare staff, highlighting the importance of expanding occupational health policies to non-clinical hospital staff. Further spread into an under-vaccinated Traveller community is a reminder that measles can spread in the absence of herd immunity. Subsequently endemic measles transmission has been re-established in the UK.

SETTING AND OBJECTIVES: There is an urgent need to improve tuberculosis (TB) case detection globally. This would require greater focus on the implementation of TB screening programs. However, to be productive, cost-effective, and ethical, TB screening efforts should be tailored to their local context, targeted to the populations most likely to benefit and utilizing diagnostic tools with sufficient accuracy.DESIGN AND RESULTS: We have developed an online tool, ScreenTB to help National TB Programmes (NTPs) and their partners plan TB screening activities by modeling the potential outcomes of screening programs, including yield of TB cases diagnosed (true- and false-positives), costs, and cost-effectiveness, specific to the populations screened and the diagnostic algorithms used. In Myanmar, ScreenTB was used to assist the NTP in prioritizing risk groups for screening efforts and selecting appropriate screening algorithms to maximize case detection and minimize false-positive diagnoses.CONCLUSION: The ScreenTB tool can help facilitate the prioritization of risk groups for screening and the selection of appropriate screening algorithms. This is useful when used as part of a larger planning process that considers feasibility of screening, vulnerability of risk groups, potential impact of screening on TB transmission, human rights implications of screening and equity in health care access.

There has been an ongoing debate in the healthcare community about what pressure ulcers/injuries are, and how to name, define and classify them. The aim of this discussion paper is to provide a brief theoretical background about pressure ulcer/injury classification, to explain the approach the Guideline Governance Group has taken during the 2019 update of the International Guideline for 'Prevention and Treatment of Pressure Ulcers/Injuries' and to share views on how to best implement pressure ulcer/injury classification. First formal pressure ulcer/injury classifications were introduced in the 1950s and today various pressure ulcer/injury classification systems are used worldwide. Dissimilarities between commonly used classification systems may be considered a limitation that impedes clinical and scientific communication. However, the conceptual meaning of pressure ulcer/injury categories described within the various classification systems is comparable and the current evidence does not indicate that one classification is superior to another. Therefore, the Guideline Governance Group created a crosswalk of the major pressure ulcer/injury classifications in common use across different geographic regions. Clinicians are encouraged to use the classification system adopted by their healthcare setting in the most consistent way. The validity of pressure ulcer/injury classification is closely linked to its intended purpose. Studying measurement properties of pressure ulcer/injury classification systems must follow state-of-the-art methods. Structured educational interventions are helpful for improving diagnostic accuracy and reducing misclassification of pressure ulcers/injuries. Implementation of innovative skin and soft tissue assessments and revised pressure ulcer/injury classifications are only worth implementing, when the diagnostic information improves clinical care.