Management of Monogenic and Syndromic Obesity.

Similar to the general population, lifestyle interventions focused on nutrition and physical activity form the foundation for treating obesity caused by rare genetic disorders. Additional therapies, including metreleptin and setmelanotide, that target defects within the leptin signaling pathway can effectively synergize with lifestyle efforts to treat monogenic disorders of leptin, leptin receptor, proopiomelanocortin (POMC), and proprotein convertase subtilisin/kexin type 1 (PCSK1) and syndromic conditions, such as the ciliopathies Bardet-Biedl and Alström syndromes, whose pathophysiological mechanisms also converge on the leptin pathway. Investigational treatments for Prader-Willi syndrome target specific defects caused by reduced expression of paternally derived genes within the chromosome 15q region.

SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2.

In this study we profiled vaccine-induced polyclonal antibodies as well as plasmablast-derived mAbs from individuals who received SARS-CoV-2 spike mRNA vaccine. Polyclonal antibody responses in vaccinees were robust and comparable to or exceeded those seen after natural infection. However, the ratio of binding to neutralizing antibodies after vaccination was greater than that after natural infection and, at the monoclonal level, we found that the majority of vaccine-induced antibodies did not have neutralizing activity. We also found a co-dominance of mAbs targeting the NTD and RBD of SARS-CoV-2 spike and an original antigenic-sin like backboost to spikes of seasonal human coronaviruses OC43 and HKU1. Neutralizing activity of NTD mAbs but not RBD mAbs against a clinical viral isolate carrying E484K as well as extensive changes in the NTD was abolished, suggesting that a proportion of vaccine-induced RBD binding antibodies may provide substantial protection against viral variants carrying single E484K RBD mutations.

The plasmablast response to SARS-CoV-2 mRNA vaccination is dominated by non-neutralizing antibodies and targets both the NTD and the RBD.

In this study we profiled vaccine-induced polyclonal antibodies as well as plasmablast derived mAbs from individuals who received SARS-CoV-2 spike mRNA vaccine. Polyclonal antibody responses in vaccinees were robust and comparable to or exceeded those seen after natural infection. However, the ratio of binding to neutralizing antibodies after vaccination was greater than that after natural infection and, at the monoclonal level, we found that the majority of vaccine-induced antibodies did not have neutralizing activity. We also found a co-dominance of mAbs targeting the NTD and RBD of SARS-CoV-2 spike and an original antigenic-sin like backboost to seasonal human coronaviruses OC43 and HKU1. Neutralizing activity of NTD mAbs but not RBD mAbs against a clinical viral isolate carrying E484K as well as extensive changes in the NTD was abolished, suggesting that a proportion of vaccine induced RBD binding antibodies may provide substantial protection against viral variants carrying single E484K RBD mutations.

Reducing intraocular-pressure spike after intravitreal-bevacizumab injection with ocular decompression using a sterile cotton swab soaked in proparacaine 0.5%: A quasi-experimental study.

BACKGROUND/PURPOSE: The study was conducted to determine the effect of preinjection ocular decompression by a cotton swab soaked in local anesthetic on the immediate postinjection rise in intraocular pressure (IOP) after intravitreal bevacizumab (IVB). METHODS: A nonrandomized, quasi-experimental interventional study was conducted at Al-Shifa Trust Eye Hospital, Pakistan, from August 1, 2013 to July 31, 2014. One hundred (n = 100) patients receiving 0.05-mL IVB injection for the first time were assigned to two preinjection anesthetic methods: one with ocular decompression using a sterile cotton swab soaked in proparacaine 0.5%, and the other without ocular decompression using proparacaine 0.5% eyedrops. The IOP was recorded in the eye receiving IVB at three time intervals: Time 1 (preinjection), Time 2 (immediately after injection), and Time 3 (30 minutes after injection). RESULTS: There was a significant difference in the mean IOP change (between Time 1 and Time 2) for the group injected with ocular decompression [M = 1.00, standard deviation (SD) = 1.47] and the group injected without ocular decompression (M = 5.00, SD = 2.38; t (68) = 9.761, p < 0.001). There was also a significant difference in the mean IOP change (between Time 1 and Time 3) for the group injected with ocular decompression (M = 0.428, SD = 1.58) and the group injected without ocular decompression (M = 4.318, SD = 3.34; t (58) = 7.111, p < 0.001). CONCLUSION: Patients receiving IVB injections with ocular-decompression soaking in proparacaine 0.5% experience significantly lower postinjection IOP spike, and that too for a considerably shorter duration as compared to those receiving IVB without ocular decompression.

Vein of Galen aneurysmal malformation masquerading as carotid cavernous fistula in a child with proptosis.

PURPOSE: An infant with proptosis and dilated episcleral vessels was diagnosed with vein of Galen malformation, which is a rare condition presenting initially to an ophthalmologist. METHODS: An 8-month-old child presented with slowly progressive proptosis of the left eye of 5 months' duration. The proptosis was axial, nonpulsatile, with no associated bruit. Dilated corkscrew episcleral vessels were observed. The patient was referred to our center with diagnosis of carotid cavernous fistula. The child had a history of episodes of seizures. RESULTS: Contrast-enhanced computed tomographic scan of the patient showed dilated vessels, hydrocephalus, and dilated vein of Galen. Vein of Galen aneurysmal malformation was confirmed on magnetic resonance venography. CONCLUSIONS: Occasionally patients with Vein of Galen aneurysmal malformation may first present to the ophthalmologist. Ophthalmologists should therefore be aware of this rare but potentially treatable condition.