Governments around the world are responding to the coronavirus disease 2019 (COVID-19) pandemic
, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with unprecedented policies ...designed to slow the growth rate of infections. Many policies, such as closing schools and restricting populations to their homes, impose large and visible costs on society; however, their benefits cannot be directly observed and are currently understood only through process-based simulations
. Here we compile data on 1,700 local, regional and national non-pharmaceutical interventions that were deployed in the ongoing pandemic across localities in China, South Korea, Italy, Iran, France and the United States. We then apply reduced-form econometric methods, commonly used to measure the effect of policies on economic growth
, to empirically evaluate the effect that these anti-contagion policies have had on the growth rate of infections. In the absence of policy actions, we estimate that early infections of COVID-19 exhibit exponential growth rates of approximately 38% per day. We find that anti-contagion policies have significantly and substantially slowed this growth. Some policies have different effects on different populations, but we obtain consistent evidence that the policy packages that were deployed to reduce the rate of transmission achieved large, beneficial and measurable health outcomes. We estimate that across these 6 countries, interventions prevented or delayed on the order of 61 million confirmed cases, corresponding to averting approximately 495 million total infections. These findings may help to inform decisions regarding whether or when these policies should be deployed, intensified or lifted, and they can support policy-making in the more than 180 other countries in which COVID-19 has been reported
.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Digital ocular massage has been reported to temporarily lower intraocular pressure (IOP). This could be related to an enhanced aqueous humor outflow; however, the mechanism is not clearly understood. ...Using anterior segment optical coherence tomography, the Schlemm's canal (SC) and trabecular meshwork (TM) can be imaged and measured. Here, 66 healthy adults underwent digital ocular massage for 10 min in their right eyes. The IOP and dimensions of the SC and TM were measured before and after ocular massage. All subjects demonstrated IOP reduction from 15.7 ± 2.5 mmHg at baseline to 9.6 ± 2.2 mmHg immediately after, and median of 11.6 mmHg 5-min after ocular massage (Friedman's test, p < 0.001). There was significant change in SC area (median 10,063.5 μm
at baseline to median 10,151.0 μm
after ocular massage, Wilcoxon test, p = 0.02), and TM thickness (median 149.8 μm at baseline to 144.6 ± 25.3 μm after ocular massage, Wilcoxon test, p = 0.036). One-third of the subjects demonstrated collapse of the SC area (-2 to -52%), while two-thirds showed expansion of the SC area (2 to 168%). There were no significant changes in SC diameter (270.4 ± 84.1 μm vs. 276.5 ± 68.7 μm, paired t-test, p = 0.499), and TM width (733.3 ± 110.1 μm vs. 733.5 ± 111.6 μm, paired t-test, p = 0.988). Eyes with a higher baseline IOP demonstrated a greater IOP reduction (Pearson correlation coefficient r = -0.521, p < 0.001). Eyes with smaller SC area at baseline showed greater SC area expansion (Pearson correlation coefficient = -0.389, p < 0.001). Greater IOP reduction appeared in eyes with greater SC area expansion (Pearson correlation coefficient r = -0.306, p = 0.01). Association between change in IOP and change in TM thickness was not significant (Spearman's ρ = 0.015, p = 0.902). Simple digital ocular massage is an effective method to lower IOP values, and change in the SC area was significantly associated with IOP changes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Synapse loss and Tau pathology are hallmarks of Alzheimer’s disease (AD) and other tauopathies, but how Tau pathology causes synapse loss is unclear. We used unbiased proteomic analysis of ...postsynaptic densities (PSDs) in Tau-P301S transgenic mice to identify Tau-dependent alterations in synapses prior to overt neurodegeneration. Multiple proteins and pathways were altered in Tau-P301S PSDs, including depletion of a set of GTPase-regulatory proteins that leads to actin cytoskeletal defects and loss of dendritic spines. Furthermore, we found striking accumulation of complement C1q in the PSDs of Tau-P301S mice and AD patients. At synapses, C1q decorated perisynaptic membranes, accumulated in correlation with phospho-Tau, and was associated with augmented microglial engulfment of synapses and decline of synapse density. A C1q-blocking antibody inhibited microglial synapse removal in cultured neurons and in Tau-P301S mice, rescuing synapse density. Thus, inhibiting complement-mediated synapse removal by microglia could be a potential therapeutic target for Tau-associated neurodegeneration.
•Pathological Tau accumulation alters protein composition of PSD in Tau-P301S mice•Loss of postsynaptic GTPase-regulatory proteins leads to loss of dendritic spines•C1q tags Tau-affected synapses, leading to microglial engulfment and synapse loss•C1q-blocking antibody prevents microglial synapse removal and rescues synapse density
Unbiased proteomics reveals multiple molecular changes at hippocampal synapses that occur prior to neurodegeneration in a taupathy/Alzheimer’s disease mouse model. Complement C1q labels phospho-Tau-containing synapses and drives microglia-mediated synapse loss that can be rescued by a C1q-blocking antibody.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Elbow arthroscopy is increasingly used to treat complex pathology. The purpose of this study was to investigate early complication rates after elbow arthroscopy and identify risk factors ...for adverse events. Methods Consecutive elbow arthroscopies performed during a 13-year period were reviewed, identifying early perioperative complications. Major complications included deep infection, permanent nerve injury, or complications requiring additional anesthesia. Minor complications included superficial wound complications and transient nerve palsies. Complications were compared with a surgical complexity scale based on the procedure performed, the number of arthroscopic portals, and tourniquet time. Results Of 417 procedures, there were 37 minor (8.9%) and 20 major (4.8%) complications. The rates of superficial and deep infections were 6.7% and 2.2%, respectively. Major complications included 9 deep infections, 6 cases of heterotopic ossification requiring further surgery, and 4 manipulations under anesthesia. There were 7 transient sensory nerve complications, and no motor deficits. No differences in complication rates were seen between low-, moderate-, and high-complexity (10.2%, 16.3% and 14.4%, respectively) cases. Intraoperative steroid injections were strongly associated with postoperative superficial (14.1% vs 2.0%) and deep infection (4.9% vs 0.4%) in elbows receiving vs those not receiving steroid ( P < .0001). Conclusions Complications of elbow arthroscopy are seen in approximately 14% of cases. Most complications are minor, not affecting clinical outcome. Major complications occur in 5% of cases, often requiring repeat surgery. Intraoperative postsurgical steroid injections are associated with increased risk of perioperative infections. Case complexity does not appear to affect the rate of complications with modern surgical techniques.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
is an Alzheimer's disease (AD) risk gene expressed in microglia. To study the role of
in a mouse model of β-amyloidosis, we compared PS2APP transgenic mice versus PS2APP mice lacking
(PS2APP;Trem2
) ...at ages ranging from 4 to 22 months. Microgliosis was impaired in PS2APP;Trem2
mice, with
-deficient microglia showing compromised expression of proliferation/Wnt-related genes and marked accumulation of ApoE. Plaque abundance was elevated in PS2APP;Trem2
females at 6-7 months; but by 12 or 19-22 months of age, it was notably diminished in female and male PS2APP;Trem2
mice, respectively. Across all ages, plaque morphology was more diffuse in PS2APP;Trem2
brains, and the Aβ42:Aβ40 ratio was elevated. The amount of soluble, fibrillar Aβ oligomers also increased in PS2APP;Trem2
hippocampi. Associated with these changes, axonal dystrophy was exacerbated from 6 to 7 months onward in PS2APP;Trem2
mice, notwithstanding the reduced plaque load at later ages. PS2APP;Trem2
mice also exhibited more dendritic spine loss around plaque and more neurofilament light chain in CSF. Thus, aggravated neuritic dystrophy is a more consistent outcome of
deficiency than amyloid plaque load, suggesting that the microglial packing of Aβ into dense plaque is an important neuroprotective activity.
Genetic studies indicate that
gene mutations confer increased Alzheimer's disease (AD) risk. We studied the effects of
deletion in the PS2APP mouse AD model, in which overproduction of Aβ peptide leads to amyloid plaque formation and associated neuritic dystrophy. Interestingly, neuritic dystrophies were intensified in the brains of
-deficient mice, despite these mice displaying reduced plaque accumulation at later ages (12-22 months). Microglial clustering around plaques was impaired, plaques were more diffuse, and the Aβ42:Aβ40 ratio and amount of soluble, fibrillar Aβ oligomers were elevated in
-deficient brains. These results suggest that the Trem2-dependent compaction of Aβ into dense plaques is a protective microglial activity, limiting the exposure of neurons to toxic Aβ species.
Complement pathway overactivation can lead to neuronal damage in various neurological diseases. Although Alzheimer’s disease (AD) is characterized by β-amyloid plaques and tau tangles, previous work ...examining complement has largely focused on amyloidosis models. We find that glial cells show increased expression of classical complement components and the central component C3 in mouse models of amyloidosis (PS2APP) and more extensively tauopathy (TauP301S). Blocking complement function by deleting C3 rescues plaque-associated synapse loss in PS2APP mice and ameliorates neuron loss and brain atrophy in TauP301S mice, improving neurophysiological and behavioral measurements. In addition, C3 protein is elevated in AD patient brains, including at synapses, and levels and processing of C3 are increased in AD patient CSF and correlate with tau. These results demonstrate that complement activation contributes to neurodegeneration caused by tau pathology and suggest that blocking C3 function might be protective in AD and other tauopathies.
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•Increased glial classical complement expression in amyloidosis and tauopathy models•C3 deficiency rescues plaque-proximal synapse loss in PS2APP mice•C3 deficiency mitigates neurodegeneration and neuronal loss in TauP301S mice•C3 protein is increased in brains and cerebrospinal fluid from AD patients
Wu et al. show that loss of the central complement component C3, which is elevated and activated in brains and cerebrospinal fluid from AD patients, ameliorates synapse loss and neurodegeneration in amyloidosis and tauopathy AD mouse models despite ongoing glial activation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The injury severity score (ISS) is used in daily practice to evaluate the severity of trauma patients; however, the score is not always consistent with the prognosis. After injury, systemic ...inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS) are related to the prognosis of trauma patients. We aimed to evaluate the associations between the immune response and prognosis in trauma patients. Patients who admitted to the Trauma Intensive Care Unit (ICU) were eligible. Whole blood samples were collected at admission, and then 6, 12, 24, 48 and 72 h after admission. Natural killer (NK) cells, lymphocyte subset population and cytokines release were identified using flow cytometry. We grouped patients by their ISS (≤ 25 and > 25 as very severe injury) and ICU stay (≤ 10 days as a short ICU stay and > 10 days as a long ICU stay) for evaluation. Fifty-three patients were enrolled. ICU stay but not ISS was close correlated with activity daily living (ADL) at discharge. Patients with a long ICU stay had an immediate increase in NK cells followed by lymphopenia which persisted for 48 h. Immediate activation of CD8
T cells and then exhaustion with a higher programmed cell death-1 (PD-1) expression and suppression of CD4
T cells with a shift to an anti-inflammatory Th2 phenotype were also observed in the patients with a long ICU stay. When the patients were grouped by ISS, the dynamics of immune responses were inconsistent to those when the patients were grouped by ICU stay. Immune responses are associated with the prognosis of trauma patients, however the currently used clinical parameters may not accurately reflect immune responses. Further investigations are needed to identify accurate predictors of prognosis in trauma patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose
Trachoma, the world's leading infectious cause of blindness, has been targeted by the WHO for elimination through the SAFE strategy: surgery, antibiotics, facial cleanliness, and ...environmental improvement. Although significant progress has been made, there remains a gap in care. This project studied the association of geographical distribution of the remaining need for trachoma intervention and its association with access to basic handwashing facilities at home, as an indicator of water/sanitation infrastructure. We hypothesized that poor water sanitation would correspond to areas where trachoma intervention is still required.
Design
Retrospective analysis using the WHO Global Health Observatory. Spatial, correlation, and simple and multivariable regression analyses were used.
Methods
Using data from the WHO Global Health Observatory, a total of 194 countries were analyzed. Two choropleth maps were created, with inset maps focused on the South Pacific region, where the top 5 countries with the greatest population proportion requiring trachoma intervention are located.
Results
Correlations and the simple regression model of total population with access to handwashing facilities as the only risk factor were insignificant. However, the multivariable regression models with access to handwashing facilities (total, urban, and rural) and population density as risk factors for trachoma intervention were significant.
Conclusion
Poor water/sanitation infrastructure correlates with trachoma burden. Therefore, water/sanitation infrastructure improvement is a worthwhile target in the efforts toward trachoma elimination, but further research on the association between these important public health indicators is warranted.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Pachyonychia congenita (PC) is a genetic disorder of keratin that presents with nail dystrophy, painful palmoplantar keratoderma, and other clinical manifestations. We investigated the ...genotype‒structurotype‒phenotype correlations seen with mutations in keratin genes (keratin K6A, K6B, K6C, K16, K17) and utilized protein structure modeling of high-frequency mutations to examine the functional importance of keratin structural domains in PC pathogenesis. Participants of the International PC Research Registry underwent genetic testing and completed a standardized survey on their symptoms. Our results support previous reports associating oral leukokeratosis with K6A mutations and cutaneous cysts, follicular hyperkeratosis, and natal teeth with K17 mutations. Painful keratoderma was prominent with K6A and K16 mutations. Nail involvement was most common in patients with K6A mutation and least common in those with K6C mutation. Across keratin subtypes, patients with coil 2B mutations had the greatest impairment in ambulation, and patients with coil 1A mutations reported more emotional issues. Molecular modeling demonstrated that hotspot missense mutations in PC largely disrupted hydrophobic interactions or surface charge. The former may destabilize keratin dimers/tetramers, whereas the latter likely interferes with higher-order keratin filament formation. Understanding the pathologic alterations in keratin structure improves our knowledge of how PC genotype correlates with clinical phenotype, advancing insight into disease pathogenesis and therapeutic development.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background/Objective Exercise-based rehabilitation is a conservative management approach for individuals with low back pain. However, adherence rates for conservative management are often low and the ...reasons for this are not well described. The objective of this study was to evaluate predictors of adherence and patient-reported reasons for non-adherence after ceasing a supervised exercise-based rehabilitation program in individuals with low back pain. Design Retrospective observational study. Methods Data was retrospectively analyzed from 5 rehabilitation clinics utilizing a standardized exercise-based rehabilitation program. Baseline demographics, diagnosis and symptom specific features, visit number, and discontinuation profiles were quantified for 2,243 patients who underwent the program. Results Forty-three percent (43%) of participants were adherent to the program, with the majority (31.7%) discontinuing treatment prior to completion due to logistic and accessibility issues. Another 13.2% discontinued prior to the prescribed duration due to clinically significant improvements in pain and/or disability without formal discharge evaluation, whereas 8.3% did not continue due to lack of improvement. Finally, 6.0% were discharged for related and unrelated medical reasons including surgery. Individuals diagnosed with disc pathology were most likely to be adherent to the program. Limitations This study was a retrospective chart review with missing data for some variables. Future studies with a prospective design would increase quality of evidence. Conclusions The majority of individuals prescribed an in-clinic exercise-based rehabilitation program are non-adherent. Patient diagnosis was the most important predictor of adherence. For those who were not adherent, important barriers include personal issues, insufficient insurance authorization and lack of geographic accessibility.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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