Kv3.3 Channels Bind Hax-1 and Arp2/3 to Assemble a Stable Local Actin Network that Regulates Channel Gating.

Mutations in the Kv3.3 potassium channel (KCNC3) cause cerebellar neurodegeneration and impair auditory processing. The cytoplasmic C terminus of Kv3.3 contains a proline-rich domain conserved in proteins that activate actin nucleation through Arp2/3. We found that Kv3.3 recruits Arp2/3 to the plasma membrane, resulting in formation of a relatively stable cortical actin filament network resistant to cytochalasin D that inhibits fast barbed end actin assembly. These Kv3.3-associated actin structures are required to prevent very rapid N-type channel inactivation during short depolarizations of the plasma membrane. The effects of Kv3.3 on the actin cytoskeleton are mediated by the binding of the cytoplasmic C terminus of Kv3.3 to Hax-1, an anti-apoptotic protein that regulates actin nucleation through Arp2/3. A human Kv3.3 mutation within a conserved proline-rich domain produces channels that bind Hax-1 but are impaired in recruiting Arp2/3 to the plasma membrane, resulting in growth cones with deficient actin veils in stem cell-derived neurons.

Modulation of potassium conductances optimizes fidelity of auditory information.

Potassium channels in auditory neurons are rapidly modified by changes in the auditory environment. In response to elevated auditory stimulation, short-term mechanisms such as protein phosphorylation and longer-term mechanisms such as accelerated channel synthesis increase the amplitude of currents that promote high-frequency firing. It has been suggested that this allows neurons to fire at high rates in response to high sound levels. We have carried out simple simulations of the response to postsynaptic neurons to patterns of neurotransmitter release triggered by auditory stimuli. These demonstrate that the amplitudes of potassium currents required for optimal encoding of a low-amplitude auditory signal differ from those for louder sounds. Specifically, the cross-correlation of the output of a neuron with an auditory stimulus is improved by increasing potassium currents as sound amplitude increases. Temporal fidelity for low-frequency stimuli is improved by increasing potassium currents that activate at negative potentials, while that for high-frequency stimuli requires increases in currents that activate at positive membrane potentials. These effects are independent of the firing rate. Moreover, levels of potassium currents that maximize the fidelity of the output of an ensemble of neurons differ from those that maximize fidelity for a single neuron. This suggests that the modulatory mechanisms must coordinate channel activity in groups of neurons or an entire nucleus. The simulations provide an explanation for the modulation of the intrinsic excitability of auditory brainstem neurons by changes in environmental sound levels, and the results may extend to information processing in other neural systems.

Kv3 Channels: Enablers of Rapid Firing, Neurotransmitter Release, and Neuronal Endurance.

The intrinsic electrical characteristics of different types of neurons are shaped by the K+ channels they express. From among the more than 70 different K+ channel genes expressed in neurons, Kv3 family voltage-dependent K+ channels are uniquely associated with the ability of certain neurons to fire action potentials and to release neurotransmitter at high rates of up to 1,000 Hz. In general, the four Kv3 channels Kv3.1-Kv3.4 share the property of activating and deactivating rapidly at potentials more positive than other channels. Each Kv3 channel gene can generate multiple protein isoforms, which contribute to the high-frequency firing of neurons such as auditory brain stem neurons, fast-spiking GABAergic interneurons, and Purkinje cells of the cerebellum, and to regulation of neurotransmitter release at the terminals of many neurons. The different Kv3 channels have unique expression patterns and biophysical properties and are regulated in different ways by protein kinases. In this review, we cover the function, localization, and modulation of Kv3 channels and describe how levels and properties of the channels are altered by changes in ongoing neuronal activity. We also cover how the protein-protein interaction of these channels with other proteins affects neuronal functions, and how mutations or abnormal regulation of Kv3 channels are associated with neurological disorders such as ataxias, epilepsies, schizophrenia, and Alzheimer's disease.

Gynecomastia Surgery Patient Education: An Information Quality Assessment of YouTube Videos.

BACKGROUND: YouTube is a platform for many topics, including plastic surgery. Previous studies have shown poor educational value in YouTube videos of plastic surgery procedures. The purpose of this study was to evaluate the quality and accuracy of YouTube videos concerning gynecomastia surgery (GS). METHODS: The phrases "gynecomastia surgery" (GS) and "man boobs surgery" (MB) were queried on YouTube. The first 50 videos for each search term were examined. The videos were rated using our novel Gynecomastia Surgery Specific Score to measure gynecomastia-specific information, the Patient Education Materials Assessment Tool (PEMAT) to measure understandability and actionability, and the Global Quality Scale to measure general quality. RESULTS: The most common upload source was a board-certified plastic surgeon (35%), and content category was surgery techniques and consultations (51%). Average scores for the Global Quality Scale (x̄ = 2.25), Gynecomastia Surgery Specific Score (x̄ = 3.50), and PEMAT Actionability (x̄ = 44.8%) were low, whereas PEMAT Understandability (x̄ = 77.4%) was moderate to high. There was no difference in all scoring modalities between the GS and MB groups. Internationally uploaded MB videos tended to originate from Asian countries, whereas GS videos tended to originate from non-US Western countries. Patient uploaders had higher PEMAT Actionability scores than plastic surgeon uploaders. CONCLUSIONS: The quality and amount of gynecomastia-specific information in GS videos on YouTube are low and contain few practical, take-home points for patients. However, understandability is adequate. Plastic surgeons and professional societies should strive to create high-quality medical media on platforms such as YouTube.

Disparities in eye clinic patient encounters among patients requiring language interpreter services.

BACKGROUND: Communication barriers are a major cause of health disparities for patients with limited English proficiency (LEP). Medical interpreters play an important role in bridging this gap, however the impact of interpreters on outpatient eye center visits has not been studied. We aimed to evaluate the differences in length of eyecare visits between LEP patients self-identifying as requiring a medical interpreter and English speakers at a tertiary, safety-net hospital in the United States. METHODS: A retrospective review of patient encounter metrics collected by our electronic medical record was conducted for all visits between January 1, 2016 and March 13, 2020. Patient demographics, primary language spoken, self-identified need for interpreter and encounter characteristics including new patient status, patient time waiting for providers and time in room were collected. We compared visit times by patient's self-identification of need for an interpreter, with our main outcomes being time spent with ophthalmic technician, time spent with eyecare provider, and time waiting for eyecare provider. Interpreter services at our hospital are typically remote (via phone or video). RESULTS: A total of 87,157 patient encounters were analyzed, of which 26,443 (30.3%) involved LEP patients identifying as requiring an interpreter. After adjusting for patient age at visit, new patient status, physician status (attending or resident), and repeated patient visits, there was no difference in the length of time spent with technician or physician, or time spent waiting for physician, between English speakers and patients identifying as needing an interpreter. Patients who self-identified as requiring an interpreter were more likely to have an after-visit summary printed for them, and were also more likely to keep their appointment once it was made when compared to English speakers. CONCLUSIONS: Encounters with LEP patients who identify as requiring an interpreter were expected to be longer than those who did not indicate need for an interpreter, however we found that there was no difference in the length of time spent with technician or physician. This suggests providers may adjust their communication strategy during encounters with LEP patients identifying as needing an interpreter. Eyecare providers must be aware of this to prevent negative impacts on patient care. Equally important, healthcare systems should consider ways to prevent unreimbursed extra time from being a financial disincentive for seeing patients who request interpreter services.

Undernutrition among the children below five years of age in Uganda: a spatial analysis approach.

BACKGROUND: Undernutrition is a health condition caused by a lack of enough food intake, not having enough of the right combination of food nutrients, or the body's failure to utilize the food eaten resulting in either, stunting, being underweight, or wasting. Globally, undernutrition affects more than 149 million under-five children, while in Uganda about 3 in every 10 children suffer from undernutrition. Undernutrition and its risk factors among under-five children in Uganda were unevenly distributed across the country and a study that focused on spatial distribution was prudent to examine the nature of the problem and salient factors associated with it. The current study addressed the issues of spatial heterogeneity of undernutrition and its determinants with the goal to identify hot spots and advise policymakers on the best actions to be taken to address the problem. METHODS: Data were obtained from the 2016 Uganda Demographic and Health Survey. Prevalence rates and percentages of risk factors were combined with the Uganda district shape file to allow spatial analysis. Moran's I, Getis-Ord (GI*), and Geographically Weighted Regressions were respectively used to establish the local, global, and geographically weighted regressions across the country. Stata 15 and ArcGIS 10. 7 soft wares were used. RESULTS: The results indicate that undernutrition in Uganda shows varies spatially across regions. Evidence of hot spots exists in the Karamoja and Arua regions, cold spot areas exist around the central part of the country while the greatest part of Western Uganda, Northern, and Eastern were not significant. CONCLUSION: The study reveals that a variation in the distribution of undernutrition throughout the country. Significant spatial patterns associated with undernutrition as identified through the hotspot and cold spot analysis do exist in Uganda. Programs targeting to reduce the undernutrition of under-five children in Uganda should consider the spatial distribution of undernutrition and its determinants whereby priority should be given to hotspot areas. The spatial intensity of undernutrition and its determinants indicate that focus should be tailored to meet the local needs as opposed to a holistic national approach.

Auditory brainstem development of naked mole-rats (Heterocephalus glaber).

Life underground often leads to animals having specialized auditory systems to accommodate the constraints of acoustic transmission in tunnels. Despite living underground, naked mole-rats use a highly vocal communication system, implying that they rely on central auditory processing. However, little is known about these animals' central auditory system, and whether it follows a similar developmental time course as other rodents. Naked mole-rats show slowed development in the hippocampus suggesting they have altered brain development compared to other rodents. Here, we measured morphological characteristics and voltage-gated potassium channel Kv3.3 expression and protein levels at different key developmental time points (postnatal days 9, 14, 21 and adulthood) to determine whether the auditory brainstem (lateral superior olive and medial nucleus of the trapezoid body) develops similarly to two common auditory rodent model species: gerbils and mice. Additionally, we measured the hearing onset of naked mole-rats using auditory brainstem response recordings at the same developmental timepoints. In contrast with other work in naked mole-rats showing that they are highly divergent in many aspects of their physiology, we show that naked mole-rats have a similar hearing onset, between postnatal day (P) 9 and P14, to many other rodents. On the other hand, we show some developmental differences, such as a unique morphology and Kv3.3 protein levels in the brainstem.

Suppression of Kv3.3 channels by antisense oligonucleotides reverses biochemical effects and motor impairment in spinocerebellar ataxia type 13 mice.

Mutations in KCNC3, the gene that encodes the Kv3.3 voltage dependent potassium channel, cause Spinocerebellar Ataxia type 13 (SCA13), a disease associated with disrupted motor behaviors, progressive cerebellar degeneration, and abnormal auditory processing. The Kv3.3 channel directly binds Hax-1, a cell survival protein. A disease-causing mutation, Kv3.3-G592R, causes overstimulation of Tank Binding Kinase 1 (Tbk1) in the cerebellum, resulting in the degradation of Hax-1 by promoting its trafficking into multivesicular bodies and then to lysosomes. We have now tested the effects of antisense oligonucleotides (ASOs) directed against the Kv3.3 channel on both wild type mice and those bearing the Kv3.3-G592R-encoding mutation. Intracerebroventricular infusion of the Kcnc3-specific ASO suppressed both mRNA and protein levels of the Kv3.3 channel. In wild-type animals, this produced no change in levels of activated Tbk1, Hax-1 or Cd63, a tetraspanin marker for late endosomes/multivesicular bodies. In contrast, in mice homozygous for the Kv3.3-G592R-encoding mutation, the same ASO reduced Tbk1 activation and levels of Cd63, while restoring the expression of Hax-1 in the cerebellum. The motor behavior of the mice was tested using a rotarod assay. Surprisingly, the active ASO had no effects on the motor behavior of wild type mice but restored the behavior of the mutant mice to those of age-matched wild type animals. Our findings indicate that, in mature intact animals, suppression of Kv3.3 expression can reverse the deleterious effects of a SCA13 mutation while having little effect on wild type animals. Thus, targeting Kv3.3 expression may prove a viable therapeutic approach for SCA13.

Global chromatin state analysis reveals lineage-specific enhancers during the initiation of human T helper 1 and T helper 2 cell polarization.

Naive CD4⁺ T cells can differentiate into specific helper and regulatory T cell lineages in order to combat infection and disease. The correct response to cytokines and a controlled balance of these populations is critical for the immune system and the avoidance of autoimmune disorders. To investigate how early cell-fate commitment is regulated, we generated the first human genome-wide maps of histone modifications that reveal enhancer elements after 72 hr of in vitro polarization toward T helper 1 (Th1) and T helper 2 (Th2) cell lineages. Our analysis indicated that even at this very early time point, cell-specific gene regulation and enhancers were at work directing lineage commitment. Further examination of lineage-specific enhancers identified transcription factors (TFs) with known and unknown T cell roles as putative drivers of lineage-specific gene expression. Lastly, an integrative analysis of immunopathogenic-associated SNPs suggests a role for distal regulatory elements in disease etiology.

The voltage-gated K+ channel Kv1.3 modulates platelet motility and α2ß1 integrin-dependent adhesion to collagen.

Kv1.3 is a voltage-gated K+-selective channel with roles in immunity, insulin-sensitivity, neuronal excitability and olfaction. Despite being one of the largest ionic conductances of the platelet surface membrane, its contribution to platelet function is poorly understood. Here we show that Kv1.3-deficient platelets display enhanced ADP-evoked platelet aggregation and secretion, and an increased surface expression of platelet integrin αIIb. In contrast, platelet adhesion and thrombus formation in vitro under arterial shear conditions on surfaces coated with collagen were reduced for samples from Kv1.3-/- compared to wild type mice. Use of collagen-mimetic peptides revealed a specific defect in the engagement with α2ß1. Kv1.3-/- platelets developed significantly fewer, and shorter, filopodia than wild type platelets during adhesion to collagen fibrils. Kv1.3-/- mice displayed no significant difference in thrombus formation within cremaster muscle arterioles using a laser-induced injury model, thus other pro-thrombotic pathways compensate in vivo for the adhesion defect observed in vitro. This may include the increased platelet counts of Kv1.3-/- mice, due in part to a prolonged lifespan. The ability of Kv1.3 to modulate integrin-dependent platelet adhesion has important implications for understanding its contribution to normal physiological platelet function in addition to its reported roles in auto-immune diseases and thromboinflammatory models of stroke.

A KCNC1 mutation in epilepsy of infancy with focal migrating seizures produces functional channels that fail to be regulated by PKC phosphorylation.

Channelopathies caused by mutations in genes encoding ion channels generally produce a clear change in channel function. Accordingly, mutations in KCNC1, which encodes the voltage-dependent Kv3.1 potassium channel, result in progressive myoclonus epilepsy as well as other developmental and epileptic encephalopathies, and these have been shown to reduce or fully abolish current amplitude. One exception to this is the mutation A513V Kv3.1b, located in the cytoplasmic C-terminal domain of the channel protein. This de novo variant was detected in a patient with epilepsy of infancy with focal migrating seizures (EIFMS), but no difference could be detected between A513V Kv3.1 current and that of wild-type Kv3.1. Using both biochemical and electrophysiological approaches, we have now confirmed that this variant produces functional channels but find that the A513V mutation renders the channel completely insensitive to regulation by phosphorylation at S503, a nearby regulatory site in the C-terminus. In this respect, the mutation resembles those in another channel, KCNT1, which are the major cause of EIFMS. Because the amplitude of Kv3.1 current is constantly adjusted by phosphorylation in vivo, our findings suggest that loss of such regulation contributes to EIFMS phenotype and emphasize the role of channel modulation for normal neuronal function.NEW & NOTEWORTHY Ion channel mutations that cause serious human diseases generally alter the biophysical properties or expression of the channel. We describe a de novo mutation in the Kv3.1 potassium channel that causes severe intellectual disability with early-onset epilepsy. The properties of this channel appear identical to those of wild-type channels, but the mutation prevents phosphorylation of the channel by protein kinase C. Our findings emphasize the role of channel modulation in normal brain function.

Mechanisms underlying auditory processing deficits in Fragile X syndrome.

Autism spectrum disorders (ASD) are strongly associated with auditory hypersensitivity or hyperacusis (difficulty tolerating sounds). Fragile X syndrome (FXS), the most common monogenetic cause of ASD, has emerged as a powerful gateway for exploring underlying mechanisms of hyperacusis and auditory dysfunction in ASD. This review discusses examples of disruption of the auditory pathways in FXS at molecular, synaptic, and circuit levels in animal models as well as in FXS individuals. These examples highlight the involvement of multiple mechanisms, from aberrant synaptic development and ion channel deregulation of auditory brainstem circuits, to impaired neuronal plasticity and network hyperexcitability in the auditory cortex. Though a relatively new area of research, recent discoveries have increased interest in auditory dysfunction and mechanisms underlying hyperacusis in this disorder. This rapidly growing body of data has yielded novel research directions addressing critical questions regarding the timing and possible outcomes of human therapies for auditory dysfunction in ASD.

Bacteria and viruses in the upper respiratory tract of Congolese children with radiologically confirmed pneumonia.

BACKGROUND: Acute pneumonia remains a leading cause of death among children below 5 years of age in the Democratic Republic of the Congo (DR Congo), despite introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in 2013. Potential pathogens in the nasopharynx of hospitalised children with pneumonia have not been studied previously in DR Congo. Here we compare clinical characteristics, risk factors and nasopharyngeal occurrence of bacteria and viruses between children with severe and non-severe pneumonia. METHODS: Between June 2015 and June 2017, 116 children aged from 2 to 59 months hospitalised due to radiologically confirmed pneumonia at Panzi referral university hospital, Bukavu, Eastern DR Congo were included in the study and sampled from nasopharynx. A multiplex real-time PCR assay for detection of 15 different viruses and 5 bacterial species was performed and another multiplex PCR assay was used for pneumococcal serotype/serogroup determination. RESULTS: During the study period 85 (73%) of the children with radiologically confirmed pneumonia met the WHO classification criteria of severe pneumonia and 31 (27%) had non-severe pneumonia. The fatality rate was 9.5%. Almost all (87%) children were treated with antibiotics before they were hospitalised, in most cases with amoxicillin (58%) or trimethoprim-sulfamethoxazole (20%). The frequency of potential pathogens in the nasopharynx of the children was high, and any viral or bacterial nucleic acids present at high levels, irrespective of species or type, were significantly associated with severe pneumonia as compared with non-severe cases (52% versus 29%, p = 0.032). White blood cell count > 20,000/µL and C-Reactive Protein > 75 mg/dL were associated with severe pneumonia at admission. Fatal outcome was in the multivariable analysis associated with having a congenital disease as an underlying condition. One or more pneumococcal serotypes/serogroups could be identified in 61 patients, and out of all identified serotypes 31/83 (37%) were non-PCV13 serotypes. CONCLUSIONS: The occurrence of any bacteria or any viruses at high levels was associated with severe pneumonia at admission. Children with congenital disorders might need a higher attention when having symptoms of acute respiratory infection, as developed pneumonia could lead to fatal outcome.

Attitudes and Perceptions Toward Virtual Health in Eye Care During Coronavirus Disease 2019.

Purpose: To evaluate attitudes and perceptions toward virtual health (VH) and its usage among eye care providers before, during, and after the coronavirus disease 2019 (COVID-19) pandemic. Materials and Methods: In April and May 2020, an online survey comprised of questions regarding past and current VH practices, as well as plans for future use was distributed among eye care providers nationwide. Results: Of the 117 eye care providers who completed the survey, 96.6% were not using VH before the COVID-19 pandemic. In contrast, 77.4% reported using VH during the pandemic. The majority of visits were for red eye (64.4%, n = 56) and ocular surface complaints (58.6%, n = 51). Examination components tested virtually varied, but most respondents felt these were at least "somewhat reliable." Almost half of respondents (45%) felt it was "very easy" or "somewhat easy" to implement VH and the majority (53.8%, n = 43) were able to get it up and running in under a week. The majority felt the transition to VH was positive (57.5%), however, only 50.4% (n = 53) of those providers planned to use VH regularly once able to see patients safely in clinic again. Conclusions: While the majority of U.S. eye care providers who responded were not using VH before the COVID-19 pandemic, just months into the U.S. outbreak, 77.4% were using VH in their daily practice. In general, providers used these platforms for urgent examinations, adnexal disease, and postoperative care most often. The majority felt the transition was a positive one, however, only half planned to continue regular use of VH once the pandemic ended.

Modulators of Kv3 Potassium Channels Rescue the Auditory Function of Fragile X Mice.

Fragile X syndrome (FXS) is characterized by hypersensitivity to sensory stimuli, including environmental sounds. We compared the auditory brainstem response (ABR) recorded in vivo in mice lacking the gene (Fmr1-/y ) for fragile X mental retardation protein (FMRP) with that in wild-type animals. We found that ABR wave I, which represents input from the auditory nerve, is reduced in Fmr1-/y animals, but only at high sound levels. In contrast, wave IV, which represents the activity of auditory brainstem nuclei is enhanced at all sound levels, suggesting that loss of FMRP alters the central processing of auditory signals. Current-clamp recordings of neurons in the medial nucleus of the trapezoid body in the auditory brainstem revealed that, in contrast to neurons from wild-type animals, sustained depolarization triggers repetitive firing rather than a single action potential. In voltage-clamp recordings, K+ currents that activate at positive potentials ("high-threshold" K+ currents), which are required for high-frequency firing and are carried primarily by Kv3.1 channels, are elevated in Fmr1-/y mice, while K+ currents that activate near the resting potential and inhibit repetitive firing are reduced. We therefore tested the effects of AUT2 [((4-({5-[(4R)-4-ethyl-2,5-dioxo-1-imidazolidinyl]-2-pyridinyl}oxy)-2-(1-methylethyl) benzonitrile], a compound that modulates Kv3.1 channels. AUT2 reduced the high-threshold K+ current and increased the low-threshold K+ currents in neurons from Fmr1-/y animals by shifting the activation of the high-threshold current to more negative potentials. This reduced the firing rate and, in vivo, restored wave IV of the ABR. Our results from animals of both sexes suggest that the modulation of the Kv3.1 channel may have potential for the treatment of sensory hypersensitivity in patients with FXS.SIGNIFICANCE STATEMENT mRNA encoding the Kv3.1 potassium channel was one of the first described targets of the fragile X mental retardation protein (FMRP). Fragile X syndrome is caused by loss of FMRP and, in humans and mice, causes hypersensitivity to auditory stimuli. We found that components of the auditory brain response (ABR) corresponding to auditory brainstem activity are enhanced in mice lacking FMRP. This is accompanied by hyperexcitability and altered potassium currents in auditory brainstem neurons. Treatment with a drug that alters the voltage dependence of Kv3.1 channels normalizes the imbalance of potassium currents, as well as ABR responses in vivo, suggesting that such compounds may be effective in treating some symptoms of fragile X syndrome.

An Epilepsy-Associated KCNT1 Mutation Enhances Excitability of Human iPSC-Derived Neurons by Increasing Slack KNa Currents.

Mutations in the KCNT1 (Slack, KNa1.1) sodium-activated potassium channel produce severe epileptic encephalopathies. Expression in heterologous systems has shown that the disease-causing mutations give rise to channels that have increased current amplitude. It is not known, however, whether such gain of function occurs in human neurons, nor whether such increased KNa current is expected to suppress or increase the excitability of cortical neurons. Using genetically engineered human induced pluripotent stem cell (iPSC)-derived neurons, we have now found that sodium-dependent potassium currents are increased several-fold in neurons bearing a homozygous P924L mutation. In current-clamp recordings, the increased KNa current in neurons with the P924L mutation acts to shorten the duration of action potentials and to increase the amplitude of the afterhyperpolarization that follows each action potential. Strikingly, the number of action potentials that were evoked by depolarizing currents as well as maximal firing rates were increased in neurons expressing the mutant channel. In networks of spontaneously active neurons, the mean firing rate, the occurrence of rapid bursts of action potentials, and the intensity of firing during the burst were all increased in neurons with the P924L Slack mutation. The feasibility of an increased KNa current to increase firing rates independent of any compensatory changes was validated by numerical simulations. Our findings indicate that gain-of-function in Slack KNa channels causes hyperexcitability in both isolated neurons and in neural networks and occurs by a cell-autonomous mechanism that does not require network interactions.SIGNIFICANCE STATEMENTKCNT1 mutations lead to severe epileptic encephalopathies for which there are no effective treatments. This study is the first demonstration that a KCNT1 mutation increases the Slack current in neurons. It also provides the first explanation for how this increased potassium current induces hyperexcitability, which could be the underlining factor causing seizures.

Sex Differences in HIV Testing - 20 PEPFAR-Supported Sub-Saharan African Countries, 2019.

Despite progress toward controlling the human immunodeficiency virus (HIV) epidemic, testing gaps remain, particularly among men and young persons in sub-Saharan Africa (1). This observational study used routinely collected programmatic data from 20 African countries reported to the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) from October 2018 to September 2019 to assess HIV testing coverage and case finding among adults (defined as persons aged ≥15 years). Indicators included number of HIV tests conducted, number of HIV-positive test results, and percentage positivity rate. Overall, the majority of countries reported higher HIV case finding among women than among men. However, a slightly higher percentage positivity was recorded among men (4.7%) than among women (4.1%). Provider-initiated counseling and testing (PITC) in health facilities identified approximately two thirds of all new cases, but index testing had the highest percentage positivity in all countries among both sexes. Yields from voluntary counseling and testing (VCT) and mobile testing varied by sex and by country. These findings highlight the need to identify and implement the most efficient strategies for HIV case finding in these countries to close coverage gaps. Strategies might need to be tailored for men who remain underrepresented in the majority of HIV testing programs.

Cataract surgery and intraocular pressure in glaucoma.

PURPOSE OF REVIEW: To review the current literature on the relationship between cataract extraction and intraocular pressure (IOP). RECENT FINDINGS: Cataract extraction can be an effective IOP lowering treatment for open and closed angle glaucoma as well as ocular hypertension. In comparative trials studying novel micro-invasive glaucoma surgeries in open angle glaucoma, the control group undergoing cataract extraction alone routinely achieved significant reductions in IOP and medication use postoperatively. Data from the Effectiveness in Angle Closure Glaucoma of Lens Extraction (EAGLE) trials have demonstrated that lens extraction is more effective at lowering IOP than peripheral iridotomy in patients with angle closure and should be considered as first line therapy. Additionally, patients in the ocular hypertension treatment study who underwent cataract extraction over the course of follow-up demonstrated significant IOP lowering sustained over 3 years. SUMMARY: Cataract extraction is an effective method to lower IOP in patients with glaucoma. Pressure lowering is more significant in eyes with narrow angles and those with higher baseline IOP levels. In eyes with angle closure, phacoemulsification alone can lower IOP, but when combined with GSL it may be even more effective. Recent large multicenter randomized trials have further elucidated the benefit of standalone cataract extraction to treat mild to moderate primary open angle glaucoma. Prospective and longitudinal studies that systematically investigate the variables that may influence degree and duration of IOP lowering post cataract extraction are lacking.

International Union of Basic and Clinical Pharmacology. C. Nomenclature and Properties of Calcium-Activated and Sodium-Activated Potassium Channels.

A subset of potassium channels is regulated primarily by changes in the cytoplasmic concentration of ions, including calcium, sodium, chloride, and protons. The eight members of this subfamily were originally all designated as calcium-activated channels. More recent studies have clarified the gating mechanisms for these channels and have documented that not all members are sensitive to calcium. This article describes the molecular relationships between these channels and provides an introduction to their functional properties. It also introduces a new nomenclature that differentiates between calcium- and sodium-activated potassium channels.

Current opinion in ophthalmology: novel glaucoma devices in the pipeline.

PURPOSE OF REVIEW: Adherence to chronic use of topical intraocular pressure (IOP) lowering medications is a fundamental barrier to successful, long-term control in patients suffering from glaucoma. This has fueled innovation to create new vehicles for drug administration, new drug formulations with enhanced bioavailability, and minimally invasive glaucoma surgeries (MIGS) with improved risk-benefit profiles to enhance sustained IOP control. The present article is an overview of novel devices in the pipeline. RECENT FINDINGS: Several new devices that promise to deliver sustained drug therapy and reduce dependence on daily patient adherence are currently being vetted through clinical trials. In addition, the pipeline for new MIGS devices that target sustained IOP control continues to grow. SUMMARY: Alternative drug delivery approaches and novel MIGS devices broaden the treatment options for patients with glaucoma. This will allow the clinician to customize treatment by selecting specific approaches based on each patient's individual needs and coexisting ocular pathologies. Additional comprehensive, large-scale, clinical studies will help define the role that these options hold in a constantly evolving treatment paradigm.