Accumulation of Immunity in Heavy-Tailed Sexual Contact Networks Shapes Mpox Outbreak Sizes.

Many countries affected by the global outbreak of mpox in 2022 have observed a decline in cases. Our mathematical model accounting for heavy-tailed sexual partnership distributions suggests that mpox epidemics can hit the infection-derived herd immunity threshold and begin to decline, with <1% of sexually active men who have sex with men infected regardless of interventions or behavioral changes. We consistently found that many countries and US states experienced an epidemic peak, with cumulative cases of around 0.1% to 0.5% among men who have sex with men. The observed decline in cases may not necessarily be attributable to interventions or behavioral changes primarily.

Age-Dependent Effects of COVID-19 Vaccine and of Healthcare Burden on COVID-19 Deaths, Tokyo, Japan.

COVID-19 vaccine effectiveness against death in Japan remains unknown. Furthermore, although evidence indicates that healthcare capacity influences case-fatality risk (CFR), it remains unknown whether this relationship is mediated by age. With a modeling study, we analyzed daily COVID-19 cases and deaths during January-August 2021 by using Tokyo surveillance data to jointly estimate COVID-19 vaccine effectiveness against death and age-specific CFR. We also examined daily healthcare operations to determine the association between healthcare burden and age-specific CFR. Among fully vaccinated patients, vaccine effectiveness against death was 88.6% among patients 60-69 years of age, 83.9% among patients 70-79 years of age, 83.5% among patients 80-89 years of age, and 77.7% among patients >90 years of age. A positive association of several indicators of healthcare burden with CFR among patients >70 years of age suggested an age-dependent effect of healthcare burden on CFR in Japan.

Estimating COVID-19 cases infected with the variant alpha (VOC 202012/01): an analysis of screening data in Tokyo, January-March 2021.

BACKGROUND: In Japan, a part of confirmed patients' samples have been screened for the variant of concern (VOC), including the variant alpha with N501Y mutation. The present study aimed to estimate the actual number of cases with variant alpha and reconstruct the epidemiological dynamics. METHODS: The number of cases with variant alpha out of all PCR confirmed cases was estimated, employing a hypergeometric distribution. An exponential growth model was fitted to the growth data of variant alpha cases over fourteen weeks in Tokyo. RESULTS: The weekly incidence with variant alpha from 18-24 January 2021 was estimated at 4.2 (95% confidence interval (CI): 0.7, 44.0) cases. The expected incidence in early May ranged from 420-1120 cases per week, and the reproduction number of variant alpha was on the order of 1.5 even under the restriction of contact from January-March, 2021, Tokyo. CONCLUSIONS: The variant alpha was predicted to swiftly dominate COVID-19 cases in Tokyo, and this has actually occurred by May 2021. Devising the proposed method, any country or location can interpret the virological sampling data.

Estimation of waning vaccine effectiveness from population-level surveillance data in multi-variant epidemics.

Monitoring time-varying vaccine effectiveness (e.g., due to waning of immunity and the emergence of novel variants) provides crucial information for outbreak control. Existing studies of time-varying vaccine effectiveness have used individual-level data, most importantly dates of vaccination and variant classification, which are often not available in a timely manner or from a wide range of population groups. We present a novel Bayesian framework for estimating the waning of variant-specific vaccine effectiveness in the presence of multi-variant circulation from population-level surveillance data. Applications to simulated outbreaks and the COVID-19 epidemic in Japan are also presented. Our results show that variant-specific waning vaccine effectiveness estimated from population-level surveillance data could approximately reproduce the estimates from previous test-negative design studies, allowing for rapid, if crude, assessment of the epidemic situation before fine-scale studies are made available.

Different time scales used for sexual partner surveys pose a challenge in modelling dynamics of sexually transmitted infections.

Mathematical models for sexually transmitted infections (STIs) are parameterised by empirical data on sexual behaviour (e.g. the number of partners over a given period) obtained from surveys. However, the time window for reporting sexual partnerships may vary between surveys and how data for different windows can be translated from one to another remains an open question. To highlight this issue, we compared the distributions of the number of sexual partners over one year and four weeks from the British National Surveys of Sexual Attitudes and Lifestyles. The results show that simple linear rescaling did not render the one-year and four-week partner distributions aligned. Parameterising STI models using survey-based sexual encounter rates without considering the implication of the reporting window used can lead to misleading results.

Chronological Change of the Clinical Features and Treatment Outcomes for Subarachnoid Hemorrhage in Japan: A Multicenter Retrospective Study.

Aneurysmal subarachnoid hemorrhage (SAH) treatment has progressed, and patients are rapidly aging in Japan. Consequently, dynamic changes must have emerged in the clinical practice of SAH. This study aimed to elucidate chronological changes of aneurysmal SAH and the prognostic factors in the previous quarter century in Japan. We conducted a retrospective survey regarding aneurysmal SAH in eight institutions in Japan. The study included 848, 863, and 781 patients in the first (1989-1993), second (1999-2003), and third (2009-2013) periods, respectively. The chronological changes of factors that influenced the poor outcomes and differences between the nonelderly (<75 years) and elderly patients were investigated. Mean age was significantly higher in patients in the third period (61.4 years) than in those in the other two periods (first, 57.8 years; second, 59.5 years). During these periods, the proportion of good outcomes did not change; however, the mortality rate significantly decreased from 19% in the first period to 11% and 9.2% in the second and third periods, respectively. The poor outcome was mainly caused by the significantly higher incidence of systemic complication and procedural complication in the first period and the significantly lower incidence of delayed ischemic neurological deficit in the third period. The elderly patients had significantly poorer clinical outcomes than the nonelderly ones. During the last 25 years, the age of patients with aneurysmal SAH has rapidly increased. The study results may contribute to the improvement of the treatment strategy of SAH in advanced countries with a rapidly aging population.

Heavy-tailed sexual contact networks and monkeypox epidemiology in the global outbreak, 2022.

The outbreak of monkeypox across non-endemic regions confirmed in May 2022 shows epidemiological features distinct from previously imported outbreaks, most notably its observed growth and predominance amongst men who have sex with men (MSM). We use a transmission model fitted to empirical sexual partnership data to show that the heavy-tailed sexual partnership distribution, in which a handful of individuals have disproportionately many partners, can explain the sustained growth of monkeypox among MSM despite the absence of such patterns previously. We suggest that the basic reproduction number (R0) for monkeypox over the MSM sexual network may be substantially above 1, which poses challenges to outbreak containment. Ensuring support and tailored messaging to facilitate prevention and early detection among MSM with high numbers of partners is warranted.

The impact of temperature on the transmissibility potential and virulence of COVID-19 in Tokyo, Japan.

Assessing the impact of temperature on COVID-19 epidemiology is critical for implementing non-pharmaceutical interventions. However, few studies have accounted for the nature of contagious diseases, i.e., their dependent happenings. We aimed to quantify the impact of temperature on the transmissibility and virulence of COVID-19 in Tokyo, Japan, employing two epidemiological measurements of transmissibility and severity: the effective reproduction number ([Formula: see text]) and case fatality risk (CFR). We estimated the [Formula: see text] and time-delay adjusted CFR and to subsequently assess the nonlinear and delayed effect of temperature on [Formula: see text] and time-delay adjusted CFR. For [Formula: see text] at low temperatures, the cumulative relative risk (RR) at the first temperature percentile (3.3 °C) was 1.3 (95% confidence interval (CI): 1.1-1.7). As for the virulence to humans, moderate cold temperatures were associated with higher CFR, and CFR also increased as the temperature rose. The cumulative RR at the 10th and 99th percentiles of temperature (5.8 °C and 30.8 °C) for CFR were 3.5 (95% CI: 1.3-10.0) and 6.4 (95% CI: 4.1-10.1). Our results suggest the importance to take precautions to avoid infection in both cold and warm seasons to avoid severe cases of COVID-19. The results and our proposed approach will also help in assessing the possible seasonal course of COVID-19 in the future.

Metastasis of Carcinoma to a Cerebral Arteriovenous Malformation.

BACKGROUND: Although carcinoma metastasis to primary intracranial neoplasms has occasionally been reported, metastasis to a cerebral arteriovenous malformation (AVM) has been exceedingly rare, with only 5 cases reported to date. In the present study, we have reported a case of lung carcinoma that had metastasized to a cerebral AVM. To the best of our knowledge, the present report is the first case in which the pathological examination detected the bleeding mechanism of this rare condition, showing destruction of the feeders by the metastatic tumor. CASE DESCRIPTION: A 61-year-old man who had had a tumor shadow in the right middle lung field identified at a medical examination 5 weeks previously had suddenly experienced a disturbance of consciousness. Head computed tomography and computed tomography angiography revealed a right occipital subcortical hemorrhage with abnormal vessels, suggesting a ruptured AVM. Magnetic resonance imaging with gadolinium-based contrast agents did not show any other lesions. Cerebral angiography revealed a Spetzler-Martin grade III AVM in the right occipital lobe. Endovascular feeder embolization and subsequent removal of the AVM were performed. Histopathological examination of the resected mass showed a small cell carcinoma that had metastasized to the AVM. The tumor cells had infiltrated to the vessel walls of the feeders, which might have elicited the bleeding. CONCLUSION: Although rare, clinicians should recognize that undifferentiated carcinomas can metastasize to AVMs and cause bleeding. Because the preoperative diagnosis can be difficult, even using the latest imaging modalities, careful examination of the resected specimen is required to reveal such pathological conditions.

Iodine-123-Iomazenil SPECT Revealed Recovery of Neuronal Viability in Association with Improvement in Symptoms Following Treatment for Obstructive Hydrocephalus due to a Giant Posterior Cerebral Artery Aneurysm.

BACKGROUND: Early and late images of 123I-iomazenil (123I-IMZ) single-photon emission computed tomography (SPECT) are considered to show cerebral blood flow and neuronal activity, respectively, and this modality may demonstrate temporal dysfunction of the frontal lobes in obstructive hydrocephalus. In this report, we examined 123I-IMZ SPECT in a patient with chronic obstructive hydrocephalus owing to compression of the aqueduct by a partially thrombosed aneurysm of the left posterior cerebral artery for the first time. CASE DESCRIPTION: A woman aged 77 years presented with progression of cognitive decline, gait disturbance, and urinary incontinence. She had a medical history of epilepsy and subarachnoid hemorrhage due to a ruptured left posterior cerebral artery aneurysm, treated conservatively when she was age 56 years. Magnetic resonance imaging revealed a mass lesion in the pineal region, which showed a target sign with gadolinium-based contrast agents, causing obstructive hydrocephalus owing to compression of the cerebral aqueduct. A right vertebral angiogram confirmed the presence of a partially thrombosed giant aneurysm at the left posterior cerebral artery. To rule out the involvement of nonconvulsive status epilepticus in her pathology, we performed 123I-IMZ SPECT, and both early and late images demonstrated low uptake in the bilateral frontal cortex. After surgical trapping of the parent artery and resection of the aneurysm, hydrocephalus was relieved, and the symptoms disappeared along with improvement in early and late 123I-IMZ SPECT images. CONCLUSIONS: The findings in the present case indicate that 123I-IMZ SPECT can detect reversible cerebral blood flow reduction and neuronal viability in the frontal lobes, which may affect the clinical manifestation of obstructive hydrocephalus.

Endoscope-Integrated Fluorescence Video Angiography for the Surgery of Ventrally Located Perimedullary Arteriovenous Fistula at Craniocervical Junction.

BACKGROUND: Intraoperative confirmation of the vascular anatomy and blood flow contributes to the safety of the surgery for perimedullary arteriovenous fistulas (PAVF). However, because the PAVF at the craniocervical junction (CCJ) is mainly located on the ventral spinal cord surface, it is difficult to observe the entire pathology by a conventional surgical approach. To achieve increased viewing angle and visualization of real time blood flow, we introduced endoscope-integrated fluorescein video angiography in the treatment for PAVF at the CCJ for the first time. CASE DESCRIPTION: A 63-year-old man presented with subarachnoid hemorrhage due to rupture of PAVF at the CCJ, fed by both the right C1 radiculomedullary artery and the anterior spinal artery (ASA). Suboccipital craniotomy and C1 hemilaminotomy was performed and microscopic observation revealed partial anatomy of the PAVF covered by subarachnoid clots on the ventrolateral surface at the right C1 nerve root level. However, pathology ventral to the C1 nerve root was obscure and an endoscope-integrated fluorescein video angiography was introduced, which clearly demonstrated the PAVF components and the ASA. CONCLUSIONS: According to these findings, the PAVF was coagulated and the ASA was preserved. Endoscope-integrated fluorescein video angiography allowed to visualize its real-time blood flow, leading to a safe and reliable treatment.

Asymmetric Synthesis of α-Alkylidene-ß-Lactams through Copper Catalysis with a Prolinol-Phosphine Chiral Ligand.

A copper/prolinol-phosphine chiral catalyst enabled the one-step synthesis of chiral α-alkylidene-ß-lactams. Optimization of the chiral ligand for steric and electronic properties realized the highly enantioselective coupling of nitrones and propargyl alcohol derived alkynes. The resulting chiral α-alkylidene-ß-lactams served as a platform for various ß-lactams via well-established transformations of α,ß-unsaturated carbonyl compounds.

Efficacy of Intraarterial Fluorescence Video Angiography in Surgery for Dural and Perimedullary Arteriovenous Fistula at Craniocervical Junction.

OBJECTIVE: Confirming the exact location of a fistula and the origins of draining veins during surgery for dural and perimedullary arteriovenous fistulas (AVFs) is crucial but sometimes inadequately performed, which can result in incomplete elimination of the lesion. Intraoperative digital subtraction angiography (DSA) is the gold standard for confirming the hemodynamics of an AVF; however, it cannot reveal the location of an AVF in the operative field. In this study, the efficacy of intraoperative intraarterial fluorescence video angiography during surgery for craniocervical junction dural and perimedullary AVFs was investigated. METHODS: We repeatedly employed this technology to evaluate its usefulness in revealing the flow dynamics and anatomy of AVFs and to confirm complete elimination of the fistula. RESULTS: Seven AVFs were included in this study. Their locations were C1 in 5 cases and C2 in 2 cases. Intraarterial fluorescence video angiography precisely revealed the locations of 3 dural AVFs, 1 perimedullary AVF, and 3 co-occurring dural and perimedullary AVFs. Frame-by-frame review of the fluorescence video angiography clearly demonstrated that fluorescence appeared earlier in the perimedullary AVF than in the draining vein through the dural AVF after intraarterial injection in all 3 co-occurring cases. Complete elimination of the AVF was also confirmed in all cases by fluorescence video angiography, as well as intraoperative and follow-up DSA. CONCLUSIONS: Intraarterial fluorescence video angiography, particularly frame-by-frame review, enables surgeons to distinguish the flow dynamics of AVFs and contributes to the planning of effective surgical strategies for optimal results.

Distribution Patterns of Spinal Epidural Fluid in Patients with Spontaneous Intracranial Hypotension Syndrome.

The aim of this study is to clarify the details of distribution patterns of spinal epidural fluid and to establish it as measure of spontaneous intracranial hypotension (SIH) syndrome diagnosis. Magnetic resonance imaging findings of the spine were analyzed in 37 patients, 24 women and 13 men (mean age 46.3 years), with SIH. Detection rate, thickness and patterns of the fluid collection were evaluated at every vertebral level. Follow-up spinal MRI findings were also analyzed for changes in epidural fluid collection and association with clinical symptoms. The MR images of the cervical spine were obtained in 30 patients, the thoracic spine in 36, and the lumbar spine in 17 patients. Epidural fluid collection was detected totally in 36 patients (97%) and was predominantly found at the mid-thoracic vertebrae. The fluid tended to locate dorsal to the dural sac at the thoracic spine and ventral at the cervical and lumbar spine. Patients with shorter duration of illness tended to have thicker fluid in the thoracic spine. In follow-up MRI, the findings of epidural fluid collection has disappeared in 32/36 cases within 3 months after treatment. Although residual fluid collection was found at the thoracic level in 4 cases, clinical symptoms were improved in all patients. This study suggested that the mid-thoracic spine should be chosen as the target of MRI in screening of SIH, and enlarged dorsal epidural space is strongly indicative of SIH.

Phosphine-Catalyzed Vicinal Acylcyanation of Alkynoates.

Phosphine organocatalysis enabled vicinal acylcyanation of alkynoates with acyl cyanides to form acrylonitrile derivatives with a tetrasubstituted alkene moiety. The acyl and cyano groups were introduced at the α and ß carbon atoms, respectively, of the C-C triple bond in the alkynoates with complete regioselectivity and high anti stereoselectivity. A variety of functional groups in the acyl cyanides and alkynoates were tolerated.

Copper(I)-catalyzed intramolecular hydroalkoxylation of unactivated alkenes.

A Cu(I)-Xantphos system catalyzed the intramolecular hydroalkoxylation of unactivated terminal alkenes, giving five- and six-membered ring ethers. This system is applicable to both primary and secondary alcohols. A reaction pathway involving the addition of the Cu-O bond across the C-C double bond is proposed. A chiral Cu(I) catalyst system based on the (R)-DTBM-SEGPHOS ligand promoted enantioselective reaction with moderate enantioselectivity.

Accurate and simple method for quantification of hepatic fat content using magnetic resonance imaging: a prospective study in biopsy-proven nonalcoholic fatty liver disease.

BACKGROUND: To assess the degree of hepatic fat content, simple and noninvasive methods with high objectivity and reproducibility are required. Magnetic resonance imaging (MRI) is one such candidate, although its accuracy remains unclear. We aimed to validate an MRI method for quantifying hepatic fat content by calibrating MRI reading with a phantom and comparing MRI measurements in human subjects with estimates of liver fat content in liver biopsy specimens. METHODS: The MRI method was performed by a combination of MRI calibration using a phantom and double-echo chemical shift gradient-echo sequence (double-echo fast low-angle shot sequence) that has been widely used on a 1.5-T scanner. Liver fat content in patients with nonalcoholic fatty liver disease (NAFLD, n = 26) was derived from a calibration curve generated by scanning the phantom. Liver fat was also estimated by optical image analysis. The correlation between the MRI measurements and liver histology findings was examined prospectively. RESULTS: Magnetic resonance imaging measurements showed a strong correlation with liver fat content estimated from the results of light microscopic examination (correlation coefficient 0.91, P < 0.001) regardless of the degree of hepatic steatosis. Moreover, the severity of lobular inflammation or fibrosis did not influence the MRI measurements. CONCLUSIONS: This MRI method is simple and noninvasive, has excellent ability to quantify hepatic fat content even in NAFLD patients with mild steatosis or advanced fibrosis, and can be performed easily without special devices.