Incidence of secondary interventions after early spica casting for diaphyseal femur fractures in young children.

BACKGROUND: Children aged 6 months to 5 years with diaphyseal femur fractures are typically treated with spica casting, as recommended by the American Association of Orthopaedic Surgeons clinical practice guideline. We aimed to determine the incidence of secondary interventions after early spica casting for femur fractures in children aged 6 years or less. METHODS: This was a retrospective cohort study of patients aged 6 years or less with diaphyseal femur fractures treated with early spica casting at a single Canadian tertiary care, level 1 trauma pediatric centre between January 2005 and May 2015. RESULTS: A total of 246 patients were included (190 boys [77.2%] and 56 girls [22.8%] with a mean age of 2.28 yr [standard deviation (SD) 1.35 yr]). Nine patients (3.7%) required early secondary interventions (cast wedging in 8 and flexible intramedullary nail fixation in 1). At last follow-up, 51 patients (20.7%) had clinically measurable limb length discrepancy (LLD) (mean 9.4 mm [SD 3-25 mm]), and 1 patient (0.4%) had mild clinical valgus deformity. Older, heavier patients with initial fracture shortening of 20 mm or more had a higher likelihood of developing a clinically measurable LLD. No patient required surgical intervention after fracture union to correct acquired LLD or angular deformity. CONCLUSION: Early spica casting for diaphyseal femoral fractures in children aged 6 years or younger had a low rate of complications and return to the operating room, Although 21% of patients had a clinically measurable LLD at last follow-up, no patient required secondary intervention after fracture union to correct acquired LLD or angular deformity. These findings have relevance for the Canadian health care system, especially during the COVID-19 pandemic.

The CLAMP protein links the MSL complex to the X chromosome during Drosophila dosage compensation.

The Drosophila male-specific lethal (MSL) dosage compensation complex increases transcript levels on the single male X chromosome to equal the transcript levels in XX females. However, it is not known how the MSL complex is linked to its DNA recognition elements, the critical first step in dosage compensation. Here, we demonstrate that a previously uncharacterized zinc finger protein, CLAMP (chromatin-linked adaptor for MSL proteins), functions as the first link between the MSL complex and the X chromosome. CLAMP directly binds to the MSL complex DNA recognition elements and is required for the recruitment of the MSL complex. The discovery of CLAMP identifies a key factor required for the chromosome-specific targeting of dosage compensation, providing new insights into how subnuclear domains of coordinate gene regulation are formed within metazoan genomes.

The essential Drosophila CLAMP protein differentially regulates non-coding roX RNAs in male and females.

Heterogametic species require chromosome-wide gene regulation to compensate for differences in sex chromosome gene dosage. In Drosophila melanogaster, transcriptional output from the single male X-chromosome is equalized to that of XX females by recruitment of the male-specific lethal (MSL) complex, which increases transcript levels of active genes 2-fold. The MSL complex contains several protein components and two non-coding RNA on the X ( roX) RNAs that are transcriptionally activated by the MSL complex. We previously discovered that targeting of the MSL complex to the X-chromosome is dependent on the chromatin-linked adapter for MSL proteins (CLAMP) zinc finger protein. To better understand CLAMP function, we used the CRISPR/Cas9 genome editing system to generate a frameshift mutation in the clamp gene that eliminates expression of the CLAMP protein. We found that clamp null females die at the third instar larval stage, while almost all clamp null males die at earlier developmental stages. Moreover, we found that in clamp null females roX gene expression is activated, whereas in clamp null males roX gene expression is reduced. Therefore, CLAMP regulates roX abundance in a sex-specific manner. Our results provide new insights into sex-specific gene regulation by an essential transcription factor.

Identification of chromatin-associated regulators of MSL complex targeting in Drosophila dosage compensation.

Sex chromosome dosage compensation in Drosophila provides a model for understanding how chromatin organization can modulate coordinate gene regulation. Male Drosophila increase the transcript levels of genes on the single male X approximately two-fold to equal the gene expression in females, which have two X-chromosomes. Dosage compensation is mediated by the Male-Specific Lethal (MSL) histone acetyltransferase complex. Five core components of the MSL complex were identified by genetic screens for genes that are specifically required for male viability and are dispensable for females. However, because dosage compensation must interface with the general transcriptional machinery, it is likely that identifying additional regulators that are not strictly male-specific will be key to understanding the process at a mechanistic level. Such regulators would not have been recovered from previous male-specific lethal screening strategies. Therefore, we have performed a cell culture-based, genome-wide RNAi screen to search for factors required for MSL targeting or function. Here we focus on the discovery of proteins that function to promote MSL complex recruitment to "chromatin entry sites," which are proposed to be the initial sites of MSL targeting. We find that components of the NSL (Non-specific lethal) complex, and a previously unstudied zinc-finger protein, facilitate MSL targeting and display a striking enrichment at MSL entry sites. Identification of these factors provides new insight into how MSL complex establishes the specialized hyperactive chromatin required for dosage compensation in Drosophila.

Sex-based differences in the anatomic distribution of cutaneous squamous cell carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy in the United States, and its incidence is increasing. Ultraviolet radiation is the main environmental risk factor for cSCCs; thus, they tend to arise on sun-exposed skin. Most publications cite the head and neck as the predominant location for cSCCs, but these papers do not account for the differential anatomic predication of cSCCs by sex. No prior studies have examined the differential distribution of cSCCs by sex, particularly invasive cSCCs that have the potential for recurrence and metastasis. OBJECTIVE: We examined the association between cSCC tumor features, including anatomic site and invasiveness, by key patient features, including age and sex. METHODS: Using an institutional cSCC registry, we identified 618 non-Hispanic white patients diagnosed with 2,111 histologically-confirmed cSCCs between 2000-2016. RESULTS: We found differential anatomic distributions of cSCC by patient sex. Men were more likely to have cSCCs arise on the head and neck (51.7%), whereas women were more likely to have cSCCs develop on the lower extremity (41.2%). Stratification by dichotomized age (younger [<65 years] vs. older [≥65 years]) revealed that nearly half of invasive cSCCs (47.7%) among older women arose on the lower extremities, whereas approximately half of the invasive cSCCs (52.4%) arose on the head and neck among older men. CONCLUSION: Lower extremities can be easily overlooked, particularly when practitioners perform waist-up-only skin examinations in time-limited settings. Understanding the anatomic predilection for invasive cSCCs by patient characteristics, including our findings, which suggest that the lower extremities are an important anatomic site for invasive cSCCs among women, can help further inform skin cancer screening and prevention efforts.

Sex-specific effects of sitting vs standing on upper body muscle activity during text typing.

Standing computer work is increasingly popular. However, despite the higher rates of computer work-related disorders in women, no studies have compared how standing work affects men and women. Twelve males and 12 females completed 90-min typing tasks in each posture while electromyography (EMG) data was recorded from eight muscles of the upper body. Results show that females had significantly higher EMG root-mean-squared (RMS) values in the anterior deltoid than males when seated, but higher EMG RMS in the medial trapezius than males when standing (SBC ≤ 0.05). In standing, they also had lower values than males in the erector spinae. Overall, standing elicited less activity in the upper trapezius, wrist extensors and erector spinae than sitting. Results suggest that the standing posture is generally less muscularly demanding than the seated one, although men and women's neck/shoulder musculature responds differently to the same task performed while seated or standing.

Multiple basal cell carcinomas in a patient with myotonic dystrophy type 1.

A man in his early 60s with myotonic dystrophy type 1 (DM1) and an extensive history of non-melanoma skin cancer presented with multiple pearly, erythematous papules on his face, head, trunk and extremities, clinically consistent with basal cell carcinoma (BCC). Due to the numerous BCC and history of multiple and early-onset BCC, examination was concerning for a hereditary BCC syndrome. Subsequent histopathology confirmed BCC. Genetic testing was negative for basal cell nevus syndrome and clinical findings were inconsistent with other known hereditary BCC syndromes. There have been reports of an association between DM1 and BCC, however, it is not well known among clinicians. We hope to raise awareness among clinicians about this association.

The Use and Relevance of the Hippocratic Oath in 2015-a Survey of US Medical Schools.

INTRODUCTION: We determined the extent and context in which the Hippocratic or other oaths are administered at accredited medical schools in the United States. METHODS: An online survey was used to gather data about oath ceremonies at every allopathic medical school in the US. RESULTS: Sixty-seven of 141 contacted medical schools (48%) had medical students recite an oath. Fifty-nine (88% of responding institutions) had students swear an oath more than once during medical training and 30 (45%) used more than one oath. Responses show that 29 (43%) schools used the classic Hippocratic Oath or a modified version of it, 29 (43%) used oaths authored by students and/or faculty, and 28 (42%) used some other oath. All reporting institutions (67, 100%) incorporated an oath into a White Coat Ceremony (62, 92%), a ceremonial event where medical students are given short white coats to be worn during clinical rotations, or Commencement (62, 93%). DISCUSSION: Oaths play a significant role in medical school ceremonies with an unknown impact on shaping the medical ethics of student physicians. Although sections of the Hippocratic Oath may seem outdated, its principles remain vastly applicable to the ethical practice of modern medicine. On the contrary, we argue that many features of the oath are more applicable than ever before to the modern clinician. We believe that the Hippocratic Oath ought to remain a vital part of today's medical education and clinical practice.