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The country's most prominent historians reflect on the significance and legacy of the Gettysburg Address.

A 69-year-old with well-controlled HIV was evaluated for persistent cough, in the context of years of fatigue and influenza A infection 6 months prior. Chest CT and PET scans were notable for adenopathy concerning for a lymphoproliferative disorder. Radiologic studies also showed diffuse FDG uptake in the prostate, consistent with prostatitis. Axillary lymph node biopsy showed follicular and paracortical hyperplasia, and few germinal centers showed perifollicular non-necrotizing granulomas. Immunohistochemical staining demonstrated a predominance of IgG4 positive plasma cells. Serum protein electrophoresis (SPEP) and immunosubtraction showed a board-domed peak pattern suggestive of possible monoclonality. Serum IgG4 levels were elevated, and the patient was diagnosed with IgG4-related disease (IgG4-RD). This case highlights morphologic and SPEP patterns that can aid in supporting a diagnosis of IgG4-RD.

Syncope is common among pediatric patients and is rarely pathologic. The mechanisms for symptoms during exercise are less well understood than the resting mechanisms. Additionally, inert gas rebreathing analysis, a non-invasive examination of haemodynamics including cardiac output, has not previously been studied in youth with neurocardiogenic syncope. This was a retrospective (2017-2023), single-center cohort study in pediatric patients ≤ 21 years with prior peri-exertional syncope evaluated with echocardiography and cardiopulmonary exercise testing with inert gas rebreathing analysis performed on the same day. Patients with and without symptoms during or immediately following exercise were noted. Of the 101 patients (15.2 ± 2.3 years; 31% male), there were 22 patients with symptoms during exercise testing or recovery. Resting echocardiography stroke volume correlated with resting ( = 0.53, < 0.0001) and peak stroke volume ( = 0.32, = 0.009) by inert gas rebreathing and with peak oxygen pulse ( = 0.61, < 0.0001). Patients with syncopal symptoms peri-exercise had lower left ventricular end-diastolic volume ( -score -1.2 ± 1.3 vs. -0.36 ± 1.3, = 0.01) and end-systolic volume ( -score -1.0 ± 1.4 vs. -0.1 ± 1.1, = 0.001) by echocardiography, lower percent predicted peak oxygen pulse during exercise (95.5 ± 14.0 vs. 104.6 ± 18.5%, = 0.04), and slower post-exercise heart rate recovery (31.0 ± 12.7 vs. 37.8 ± 13.2 bpm, = 0.03). Among youth with a history of peri-exertional syncope, those who become syncopal with exercise testing have lower left ventricular volumes at rest, decreased peak oxygen pulse, and slower heart rate recovery after exercise than those who remain asymptomatic. Peak oxygen pulse and resting stroke volume on inert gas rebreathing are associated with stroke volume on echocardiogram.

An X-linked condition characterized by the combination of hypomyelinating leukodystrophy and spondylometaphyseal dysplasia (H-SMD) has been observed in only four families, with linkage to Xq25-27, and recent genetic characterization in two families with a common AIFM1 mutation. In our study, 12 patients (6 families) with H-SMD were identified and underwent comprehensive assessment accompanied by whole-exome sequencing (WES). Pedigree analysis in all families was consistent with X-linked recessive inheritance. Presentation typically occurred between 12 and 36 months. In addition to the two disease-defining features of spondylometaphyseal dysplasia and hypomyelination on MRI, common clinical signs and symptoms included motor deterioration, spasticity, tremor, ataxia, dysarthria, cognitive defects, pulmonary hypertension, nystagmus, and vision loss due to retinopathy. The course of the disease was slowly progressive. All patients had maternally inherited or de novo mutations in or near exon 7 of AIFM1 , within a region of 70 bp, including synonymous and intronic changes. AIFM1 mutations have previously been associated with neurologic presentations as varied as intellectual disability, hearing loss, neuropathy, and striatal necrosis, while AIFM1 mutations in this small region present with a distinct phenotype implicating bone. Analysis of cell lines derived from four patients identified significant reductions in AIFM1 mRNA and protein levels in osteoblasts. We hypothesize that AIFM1 functions in bone metabolism and myelination and is responsible for the unique phenotype in this condition.

We report a role for telomerase, beyond its known function of telomeric DNA end extension, in maintaining normal chromosome dynamics during meiosis in Saccharomyces cerevisiae. When telomerase at telomeres was reduced by various genetic means, increased frequencies of crossover and noncrossover recombination events occurred. To investigate the mechanism of this increased meiotic recombination, we examined the kinetics of meiosis events, and tracked the movement of chromosomes in live cells during meiotic prophase. Cytoskeletal forces acting on telomeres during meiosis have been shown to promote active chromosome motion needed to pair homologous chromosomes. Here we show that changes in telomerase interaction with telomeres using a tlc1-11 mutant result in altered meiotic motion. Specifically, reduction in telomerase at telomeres leads to a decreased frequency of high velocity chromosome pulls. In the tlc1-11 mutant, we see earlier synapsis and increased genome-wide recombination for the majority of the cells and lower gamete viability. Notably, homologous pairing is not delayed unlike other telomere binding mutants. Although synapsis initiates earlier, the overall timing of synapsis remains the same, except for a subset of cells that do not exit meiosis I. Together, these results suggest that the strong pulling component of the active chromosome motion promotes homolog pairing fidelity, likely by pulling apart improperly associated regions. Our combined observations are consistent with a model in which telomerase-mediated telomeric anchoring to the nuclear envelope helps engage and properly transmit cytoskeletal forces to chromosomes. Thus, telomerase contributes to efficient chromosome movements leading to normal gamete viability.Competing Interest StatementThe authors have declared no competing interest.Footnotes* The manuscript has been retitled, reorganized and revised to reflect reviewer comments.

During the war in Afghanistan, President George W. Bush nicknamed Secretary of Defense Donald Rumsfeld \"Matinee Idol.\" Women of a certain age swooned over Rummy's wartime, tough-guy insouciance. But Iraq has been rough on the 72-year-old Pentagon chief. Between the Abu Ghraib scandal, the seemingly irrepressible insurgency and his recent dismissive comments about the lack of armored vehicles for U.S. troops, the pressure for Rumsfeld to step down has reached a crescendo in Washington. Sen. John McCain declared that he has \"lost confidence\" in him. Conservative commentator William Kristol slammed Rumsfeld for \"arrogant buck-passing,\" and called on Bush to replace him. Even former Senate Majority Leader Trent Lott blasted Rummy for not listening to the \"uniformed officers\" in the military. Lott's home state of Mississippi is deeply dependent on military contracts. Apparently he doesn't expect Rumsfeld to last long enough to take those contracts away. The fast lane is going to be crowded. Not only are [Burt Rutan] and his ilk pressing on with new launchings, international space agencies are planning to make 2005 a banner year in space. This spring, while Rutan builds a larger ship, for media mogul Richard Branson, NASA will put a new crew of astronauts on the space station, and says it will launch a space shuttle for the first time since the Columbia exploded upon re-entry in 2003. The coming year will also see new efforts in space by the Chinese, Japanese and Brazilians. China, which in 2004 became the third nation to launch a manned spacecraft, is planning a follow-up mission for autumn. Pioneering taiko naut Yang Liwei is competing with 13 others for the two-man orbital flight of the Shenzhou VI, which Chinese officials have said could last five to seven days. Japan's space agency, JAXA, plans to return to the cosmos for the first time since its H-2A rocket, carrying two spy satellites, veered off course in 2003 and was destroyed by mission controllers. A planned February launch will boost a multipurpose satellite to track weather and air traffic in the region. And Brazil's troubled space program also hopes to get off the ground in late 2005 with the first fully operational launch of its VSB-30 rocket. This past November, Russian President [Vladimir Putin] signed an agreement with Brazil to help modernize the launch facility and to jointly develop new rockets and communications satellites. That might be just the boost Brazil needs. North Korea is hardly a colorful place. But that doesn't mean Kim Jong Il--a big film buff himself--has killed creativity altogether. To see North Korean art at its best, the Pyongyang Art Studio in downtown Beijing--opened in August by Briton Nicholas Bonner--is the place to go. The first gallery outside of the Hermit Kingdom to deal exclusively in North Korean art carries everything from kitsch postcards and propaganda posters to sweeping landscapes painted by the country's best artists. Huang Byong Yon's \"Breaktime in the Ironwork\"--a near-photo-quality painting of two muscular men drinking water in a sweltering foundry--brims with youthful exuberance; in Jong Il Bong's 2003 ink-wash painting, \"Our Mind,\" smiling children return rainbow trout to a mountain stream, evoking an innocence seldom seen in depictions of the North.