Spatial Interaction Analysis of Infectious Disease Import and Export between Regions.

Human travel plays a crucial role in the spread of infectious disease between regions. Travel of infected individuals from one region to another can transport a virus to places that were previously unaffected or may accelerate the spread of disease in places where the disease is not yet well established. We develop and apply models and metrics to analyze the role of inter-regional travel relative to the spread of disease, drawing from data on COVID-19 in the United States. To better understand how transportation affects disease transmission, we established a multi-regional time-varying compartmental disease model with spatial interaction. The compartmental model was integrated with statistical estimates of travel between regions. From the integrated model, we derived a transmission import index to assess the risk of COVID-19 transmission between states. Based on the index, we determined states with high risk for disease spreading to other states at the scale of months, and we analyzed how the index changed over time during 2020. Our model provides a tool for policymakers to evaluate the influence of travel between regions on disease transmission in support of strategies for epidemic control.

The Postconcussion Syndrome and Posttraumatic Headaches in Civilians, Soldiers, and Athletes.

Posttraumatic headaches are one of the most common and controversial secondary headache types. After a mild traumatic brain, an estimated 11% to 82% of people develop a postconcussion syndrome, which has been controversial for more than 160 years. Headache is estimated as present in 30% to 90% of patients after a mild head injury. Most headaches are tension-type-like or migraine-like. Headaches in civilians, soldiers, athletes, and postcraniotomy are reviewed. The treatments are the same as for the primary headaches. Persistent posttraumatic headaches can continue for many years.

Socially-mediated activation in the snake social-decision-making network.

Brain areas important for social perception, social reward, and social behavior - collectively referred to as the social-decision-making network (SDN) - appear to be highly conserved across taxa. These brain areas facilitate a variety of social behaviors such as conspecific approach/avoidance, aggression, mating, parental care, and recognition. Although the SDN has been investigated across taxa, little is known about its functioning in reptiles. Research on the snake SDN may provide important new insights, as snakes have a keen social perceptual system and express a relatively reduced repertoire of social behaviors. Here, we present the results of an experiment in which ball pythons (Python regius) interacted with a same-sex conspecific for one hour and neural activation was investigated through Fos immunoreactivity. Compared to controls, snakes that interacted socially had higher Fos counts in brain areas implicated in social behavior across taxa, such as the medial amygdala, preoptic area, nucleus accumbens, and basolateral amygdala. Additionally, we found differential Fos immunoreactivity in the ventral amygdala, which facilitates communication between social brain areas. In many of these areas, Fos counts differed by sex, which may be due to increased competition between males. Fos counts did not differ in early sensory (i.e., vomeronasal) processing structures. As ball python social systems lack parental care, cooperation, or long-term group living, these results provide valuable insight into the basal functions of the vertebrate social decision-making network.

Clinical features of new daily persistent headache: A retrospective chart review of 328 cases.

OBJECTIVE: To describe the clinical features of new daily persistent headache (NDPH) at an outpatient neurology clinic with a subspecialty interest in headache in Houston, Texas. METHODS: A retrospective chart review was performed by a neurologist subspecialty certified in headache medicine of all patients seen from September 1, 2011 through February 28, 2020 (8.5 years) with a provisional diagnosis of NDPH and abstracted charts meeting criteria for primary NDPH. RESULTS: A total of 328 patients met the International Classification of Headache Disorders, 3rd edition criteria including 215 (65.5%) female patients. The mean age of onset was 40.3 years (range 12-87 years) with a mean age at first consultation in the study clinic of 42.6 years (range 12-87 years). The median [25th, 75th] duration of NDPH at initial consultation was 0.7 [0.3, 2.0] years, and at last visit, it was 1.9 [0.7, 4.8] years. The headaches were side-locked unilateral in 28/328 (8.5%). 12/328 cases (3.6%) with a thunderclap onset are reported. There was no obvious seasonal or other cyclical variation. The pain was usually moderate to severe and more often severe for the migraine phenotype (MP; 260/328 [79.3%] of cases) than for the tension-type phenotype (TTP). Precipitating factors were the following: stressful life events, 67/328 (20.4%); upper respiratory infection or flu-like illness, 33/328 (10.1%); and extracranial surgery, 5/328 (1.5%). Exacerbating or aggravating factors similar to migraine triggers were more often reported with the MP than with the TTP in this sample. For the MP, vertigo or dizziness was reported by 19/260 (7.3%) and a visual aura by 21/260 (8.1%) with descriptions provided. The prognostic types were the following for all patients: persisting (refractory), 305/328 (93.0%); relapsing-remitting, 9/328 (2.7%); and remitting (self-limited), 14/328 (4.3%). CONCLUSION: NDPH is typically of moderate to severe intensity often with migraine features without obvious seasonal or other cyclical variation. Most cases are refractory. 3.6% have a thunderclap onset often with a good response to treatment.

A brief diagnostic screen for cluster headache: Creation and initial validation of the Erwin Test for Cluster Headache.

OBJECTIVE: To use 1) newly generated data, 2) existing evidence, and 3) expert opinion to create and validate a new cluster headache screening tool. METHODS: In phase 1 of the study, we performed a prospective study of an English translation of an Italian screen on 95 participants (45 with cluster headache, 17 with other trigeminal autonomic cephalalgias, 30 with migraine, and 3 with trigeminal neuralgia). In phase 2, we performed a systematic review in PubMed of all studies until September 2019 with diagnostic screening tools for cluster headache. In phase 3, a 6-person panel of cluster headache patients, research coordinators, and headache specialists analyzed the data from the first two phases to generate a new diagnostic screening tool. Finally, in phase 4 this new screen was validated on participants at a single headache center (all diagnoses) and through research recruitment (trigeminal autonomic cephalalgias only, as recruitment was essential but was otherwise low). RESULTS: In total, this study included 319 unique participants including 109 cluster headache participants (95 total participants/45 cluster headache participants in phase 1, and 224 total participants/64 cluster headache participants in phase 4). It also found 123 articles on potential screening tools in our systematic review. In phase 1, analysis of the English translation of an Italian screen generated 7 questions with high sensitivity and specificity against migraine, trigeminal neuralgia, and other trigeminal autonomic cephalalgias, but had grammatical and other limitations as a general screening tool. In phase 2, the systematic review revealed nine studies that met inclusion criteria as diagnostic screening tools for cluster headache, including four where sensitivity and specificity were available for individual questions or small groups of questions. In phase 3, this data was reviewed by the expert panel to generate a brief (6-item), binary (yes/no), written screening test. In phase 4, a total of 224 participants completed the new 6-item screening test (81 migraine, 64 cluster headache, 21 other trigeminal autonomic cephalalgias, 35 secondary headaches, 7 neuralgias, 5 probable migraine, and 11 other headache disorders). Answers to the 6 items were combined in a decision tree algorithm and three items had a sensitivity of 84% (confidence interval or 95% confidence interval 73-92%), specificity of 89% (95% confidence interval 84-94%), positive predictive value of 76% (95% confidence interval 64-85%), and negative predictive value of 93% (95% confidence interval 88-97%) for the diagnosis of cluster headache. These three items focused on headache intensity, duration, and autonomic features. CONCLUSION: The 3-item Erwin Test for Cluster Headache is a promising diagnostic screening tool for cluster headache.

Gluten-Free Diet and Migraine.

Migraine is common in celiac disease (CD) and usually improves on a gluten-free diet (GFD). The benefit for people impacted by migraine without CD is poorly evidenced. A GFD may have adverse health consequences and is expensive.

Primary Empty Sella.

Primary empty sella (PES) syndrome is a misnomer as it is not a syndrome but a radiological finding with possible endocrine abnormalities. No specific headache type has been shown to be caused by PES. Endocrine screening may be considered for asymptomatic persons with PES.

Medico-Legal Aspects of Concussion.

Concussion and the sequelae have been controversial medico-legal issues for over 150 years. The following topics which are also important in clinical practice are discussed: definitions of concussion, neuroimaging, onset and prognosis of headaches, cognitive impairment, cognitive rehabilitation, post-traumatic stress disorder, and risk of later development of dementia.

Phase 1 study of TTC-352 in patients with metastatic breast cancer progressing on endocrine and CDK4/6 inhibitor therapy.

PURPOSE: TTC-352 is a selective human estrogen receptor (ER) partial agonist developed for treatment of hormone-refractory ER + breast cancer. METHODS: This was an accelerated dose escalation study with the primary endpoint of maximum tolerated dose that evaluated five dose levels of TTC-352 in breast cancer progressing after at least two lines of hormonal therapy including one in combination with a CDK4/6 inhibitor. The secondary objectives were to determine treatment tolerability, pharmacokinetics of TTC-352, best response, progression-free survival (PFS), and PKCα expression in tumors. RESULTS: The study enrolled 15 patients. No dose-limiting toxicity was observed. Patients experienced the following grade 3 toxicities: asymptomatic pulmonary embolism, diarrhea, aspartate transaminase elevation, and myalgia, and one grade 4 toxicity of gamma glutamyltransferase elevation. Pharmacokinetic half-life was 7.6-14.3 h. The intra- and inter-individual variability for AUC0-∞ hampered assessment of the relationship between dose and AUC0-∞. Median PFS was 58 days (95% CI = 28,112). Higher PKCα expression in tumor stroma was associated with a trend toward longer PFS. CONCLUSIONS: TTC-352 demonstrates safety and early clinical evidence of antitumor activity against heavily pretreated hormone-refractory breast cancer. Based upon TTC-352 plasma concentrations and tolerability, the 180 mg twice a day is recommended for further testing. (ClinicalTrials.gov Identifier: NCT03201913).

The Very Important Person (VIP) and the Headache Medicine Physician.

Headache medicine specialists often treat VIPs but little is known about whether these encounters are different than with other patients. Questions considered include who is a VIP, should you treat a VIP like any other patient, and what are the challenges and advantages? A non-random sampling of comments is presented from headache medicine specialists. Eleven principles are presented to consider in these encounters.

Courtship in the male red-sided garter snake is dependent on neural aromatase activity during winter dormancy.

The red-sided garter snake exhibits a dissociated reproductive pattern, mating at a time when their gonads are quiescent and circulating sex steroids, initially reported to be low, have been found to be elevated during the breeding season. However, the only cue identified that initiates courtship behavior and mating in the red-sided garter snake is an extended period of low-temperature dormancy (LTD) followed by exposure to warm temperatures. In this study, we examined a possible association between winter dormancy, sex steroid hormone metabolism, and initiation of reproductive behavior in the male red-sided garter snake. Upon emergence from winter dormancy, courtship behavior was assessed using attractive females as stimuli. Animals receiving implants containing 1,4,6-androstatriene-3,17-dione (ATD), an aromatase inhibiter, showed little or no courtship behavior, while animals implanted with ATD + 17ß estradiol (E2 ) or blank implants exhibited normal courtship. In addition, neurons in the pathways critical in the control of reproductive behavior were examined using the Golgi method. Examination of brains collected upon emergence revealed animals implanted with ATD had a significantly reduced number of dendritic spines compared to controls and animals treated with ATD + E2 . This study provides the first documentation that courtship behavior and mating in the male red-sided garter snake appears to be controlled not by LTD alone, but in conjunction with sex steroid hormones. Moreover, behavioral data suggest that the aromatization of androgens during LTD appears to be critical for the initiation of reproductive behavior in the male red-sided garter snakes.

Neuroimaging for Migraine: The American Headache Society Systematic Review and Evidence-Based Guideline.

OBJECTIVE: To provide updated evidence-based recommendations about when to obtain neuroimaging in patients with migraine. METHODS: Articles were included in the systematic review if they studied adults 18 and over who were seeking outpatient treatment for any type of migraine and who underwent neuroimaging (MRI or CT). Medline, Web of Science, and Cochrane Clinical Trials were searched from 1973 to August 31, 2018. Reviewers identified studies, extracted data, and assessed the quality of the evidence in duplicate. We assessed study quality using the Newcastle-Ottawa Scale. RESULTS: The initial search yielded 2269 publications. Twenty three articles met inclusion criteria and were included in the final review. The majority of studies were retrospective cohort or cross-sectional studies. There were 4 prospective observational studies. Ten studies evaluated the utility of CT only, 9 MRI only, and 4 evaluated both. Common abnormalities included chronic ischemia or atrophy with CT and MRI scanning, and non-specific white matter lesions with MRI. Clinically meaningful abnormalities requiring intervention were relatively rare. Clinically significant neuroimaging abnormalities in patients with headaches consistent with migraine without atypical features or red flags appeared no more common than in the general population. RECOMMENDATIONS: There is no necessity to do neuroimaging in patients with headaches consistent with migraine who have a normal neurologic examination, and there are no atypical features or red flags present. Grade A Neuroimaging may be considered for presumed migraine for the following reasons: unusual, prolonged, or persistent aura; increasing frequency, severity, or change in clinical features, first or worst migraine, migraine with brainstem aura, migraine with confusion, migraine with motor manifestations (hemiplegic migraine), late-life migraine accompaniments, aura without headache, side-locked headache, and posttraumatic headache. Most of these are consensus based with little or no literature support. Grade C.

Neuronal plasticity in the forebrain of the male red-sided garter snake: Effect of season, low temperature dormancy, and hormonal status on dendritic spine density.

Numerous studies have reported seasonal variations in regional morphology in the brains of seasonally breeding vertebrates. These alterations of neuronal morphology and dendritic spine density appear to be an active process within specific brain nuclei that regulate seasonal behaviors. In many cases, this neural plasticity has been found to be in response to changes in circulating sex steroid hormone levels and occur within pathways essential for the control of reproductive behaviors. Male red-sided garter snakes (Thamnophis sirtalis parietalis) (RSGS) exhibit a dissociated reproductive pattern where mating is initiated at a time when the gonads and steroidogenesis are inactive. And, although circulating levels of sex steroid hormones are elevated at the initiation of courtship and mating, the only known cue found to initiate courtship behavior and mating, is an extended period of low temperature dormancy (LTD) followed by exposure to warm temperatures. This study was designed to examine the role of seasons, sex steroid hormones, and LTD on neuronal and dendritic spine density within the anterior hypothalamus-preoptic area (AHPOA), a region shown to be critical for the regulation of reproductive behaviors. In the male RSGS, the density of dendritic spines on neurons in the AHPOA was significantly greater in spring, actively courting animals, than summer or fall, non-courting animals. Animals maintained under conditions of LTD exhibited significantly increasing spine density as time maintained in LTD increased. Animals receiving either testosterone or estradiol had a significantly greater density of dendritic spines than control animals. This study offers evidence suggesting that the "set up" of the pathways controlling courtship behavior and mating in the male RSGS, is not due solely to an extended period of LTD, but that an extended period of LTD in conjunction with circulating sex steroid hormones are critical for the initiation of reproductive behavior.