Alveolar macrophages help CD8+ T cells go (anti-)viral

The human immune system is a highly complex network of cells, signals, and responses that is tightly regulated to ensure that the body can fight off infection without damaging its own tissues. Now, researchers from Japan report a new way in which the immune system protects lung tissue from viral infections.
In a study published in Cell Reports, researchers from Nara Institute of Science and Technology (NAIST) have revealed that antigen-specific killer T cells (CD8+ T cells) rapidly expand in the lungs when they encounter antigen-presenting alveolar macrophages (AMs) to protect against viral infection.
CD8+ T cells confer protective immunity against infection with respiratory viruses, such as influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), by killing infected cells. In order to target the correct cells for killing, naive CD8+ T cells must be primed by contact with antigen-presenting cells (APCs), which mediate the uptake of virus-infected cells and present their antigens, in a process known as cross-presentation. The primed CD8+ T cells then clonally expand and differentiate into effector or long-lived antigen-specific memory T cells.
“Multiple cell types can present antigen to CD8+ T cells in the lungs, although the role of tissue-resident macrophages in this process is unclear,” explains Takumi Kawasaki, lead author of the study. “AMs are the first cells in the lungs that encounter infectious materials, environmental particles, surfactants, and dying cells, and they are important for the host defense against bacterial and fungal infection, so we suspected that they were also important in protecting against respiratory virus infection.”
To test this, the researchers explored the mechanisms by which APCs instruct antigen-specific CD8+ T cells in the lungs. First, mice were primed by vaccination with a specific antigen or infection with IAV, and then they were subjected to secondary immunization or re-infection.
“We determined that antigen-presenting AMs present inhaled antigen to memory CD8+ T cells,” says senior author of the study, Taro Kawai, “and that this resulted in a rapid expansion of antigen-specific CD8+ T cells in the lungs.”
Furthermore, the researchers found that AMs help to develop resident memory-type cell population by producing interleukin 18. Importantly, administration of antigen-loaded AMs to mice induced the proliferation of resident memory-type CD8+ T cells.
“This strategy may improve the efficacy of CD8+ T cell-dependent cellular immunity,” says Kawai.
Given that the lung is a major tissue for IAV and SARS-CoV-2 infection, the findings from this study regarding the mechanism of lung-resident memory CD8+ cell expansion are expected to lead to the development of new vaccines that induce cellular immunity. Virus-specific antigen-presenting AMs could be delivered as a type of “cell transplant vaccine” in the future.
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Materials provided by Nara Institute of Science and Technology. Note: Content may be edited for style and length.

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Good and bad feelings for brain stem serotonin

New insights into the opposing actions of serotonin-producing nerve fibres in mice could lead to drugs for treating addictions and major depression.
Scientists in Japan have identified a nerve pathway involved in the processing of rewarding and distressing stimuli and situations in mice.
The new pathway, originating in a bundle of brain stem nerve fibres called the median raphe nucleus, acts in opposition to a previously identified reward/aversion pathway that originates in the nearby dorsal raphe nucleus. The findings, published by scientists at Hokkaido University and Kyoto University with their colleagues in the journal Nature Communications, could have implications for developing drug treatments for various mental disorders, including addictions and major depression.
Previous studies had already revealed that activating serotonin-producing nerve fibres from the dorsal raphe nucleus in the brain stem of mice leads to the pleasurable feeling associated with reward. However, selective serotonin reuptake inhibitors (SSRIs), antidepressant drugs that increase serotonin levels in the brain, fail to exert clear feelings of reward and to treat the loss of ability to feel pleasure associated with depression. This suggests that there are other serotonin-producing nerve pathways in the brain associated with the feelings of reward and aversion.
To further study the reward and aversion nerve pathways of the brain, Hokkaido University neuropharmacologist Yu Ohmura and Kyoto University pharmacologist Kazuki Nagayasu, together with colleagues at several universities in Japan, focused their attention on the median raphe nucleus. This region has not received as much research attention as its brain stem neighbour, the dorsal raphe nucleus, even though it also is a source of serotonergic nerve fibres.
The scientists conducted a wide variety of tests to measure activity of serotonin neurons in mice, in response to stimulating and inhibiting the median raphe, by using fluorescent proteins that detect entry of calcium ions, a proxy of neuronal activation in a cell-type specific manner.
They found that, for example, pinching a mouse’s tail — an unpleasant stimulus — increased calcium-dependent fluorescence in the serotonin neurons of the median raphe. Giving mice a treat such as sugar, on the other hand, reduced median raphe serotonin fluorescence. Also, directly stimulating or inhibiting the median raphe nucleus, using a genetic technique involving light, led to aversive or reward-seeking behaviours, such as avoiding or wanting to stay in a chamber — depending on the type of stimulus applied.
The team also conducted tests to discover where the switched-on serotonergic nerve fibres of the median raphe were sending signals to and found an important connection with the brain stem’s interpenduncular nucleus. They also identified serotonin receptors within this nucleus that were involved in the aversive properties associated with median raphe serotonergic activity.
Further research is needed to fully elucidate this pathway and others related to rewarding and aversive feelings and behaviours. “These new insights could lead to a better understanding of the biological basis of mental disorders where aberrant processing of rewards and aversive information occur, such as in drug addiction and major depressive disorder,” says Ohmura.
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Materials provided by Hokkaido University. Note: Content may be edited for style and length.

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Enzyme that protects against viruses could fuel cancer evolution

An enzyme that defends human cells against viruses can help drive cancer evolution towards greater malignancy by causing myriad mutations in cancer cells, according to a study led by investigators at Weill Cornell Medicine. The finding suggests that the enzyme may be a potential target for future cancer treatments.
In the new study, published Dec. 8 in Cancer Research, scientists used a preclinical model of bladder cancer to investigate the role of the enzyme called APOBEC3G in promoting the disease and found that it significantly increased the number of mutations in tumor cells, boosting the genetic diversity of bladder tumors and hastening mortality.
“Our findings suggest that APOBEC3G is a big contributor to bladder cancer evolution and should be considered as a target for future treatment strategies,” said study senior author Dr. Bishoy M. Faltas, assistant professor of cell and developmental biology at Weill Cornell Medicine, and an oncologist who specializes in urothelial cancers at NewYork-Presbyterian/Weill Cornell Medical Center.
The APOBEC3 family of enzymes is capable of mutating RNA or DNA — by chemically modifying a cytosine nucleotide (letter “C” in the genetic code). This can result in an erroneous nucleotide at that position. The normal roles of these enzymes, including APOBEC3G, are to fight retroviruses like HIV — they attempt to hobble viral replication by mutating the cytosines in the viral genome.
The inherent hazardousness of these enzymes suggests that mechanisms must be in place to prevent them from harming cellular DNA. However, starting about a decade ago, researchers using new DNA-sequencing techniques began to find extensive APOBEC3-type mutations in cellular DNA in the context of cancer. In a 2016 study of human bladder tumor samples, Dr. Faltas, who is also director of bladder cancer research at the Englander Institute for Precision Medicine and a member of the Sandra and Edward Meyer Cancer Center, found that a high proportion of the mutations in these tumors were APOBEC3-related — and that these mutations appeared to have a role in helping tumors evade the effects of chemotherapy.
Such findings point to the possibility that cancers generally harness APOBEC3s to mutate their genomes. This could help them not only acquire all the mutations needed for cancerous growth but also boost their ability to diversify and “evolve” thereafter — enabling further growth and spread despite immune defenses, drug treatments, and other adverse factors.
In the new study, Dr. Faltas and his team, including first author Dr. Weisi Liu, a postdoctoral research associate, addressed the specific role of APOBEC3G in bladder cancer with direct cause-and-effect experiments.
APOBEC3G is a human enzyme not found in mice, so the team knocked out the gene for the sole APOBEC3-type enzyme in mice, replacing it with the gene for human APOBEC3G. The researchers observed that when these APOBEC3G mice were exposed to a bladder cancer-promoting chemical that mimics the carcinogens in cigarette smoke, they became much more likely to develop this form of cancer (76% developed cancer) compared with mice whose APOBEC gene was knocked out and not replaced (53% developed cancer). Moreover, during a 30-week observation period, all the knockout-only mice survived, whereas nearly a third of the APOBEC3G mice succumbed to cancer.
To their surprise, the researchers found that APOBEC3G in the mouse cells was present in the nucleus, where cellular DNA is kept using an ‘optical sectioning’ microscopy technique. Previously, this protein had been thought to reside only outside the nucleus. They also found that the bladder tumors of the APOBEC3G mice had about twice the number of mutations compared to the tumors in knockout-only mice.
Identifying the specific mutational signature of APOBEC3G and mapping it in the tumor genomes, the team found ample evidence that the enzyme had caused a greater mutational burden and genomic diversity in the tumors, likely accounting for the greater malignancy and mortality in the APOBEC3G mice. “We saw a distinct mutational signature caused by APOBEC3G in these tumors that is different from signatures caused by other members of the APOBEC3 family” said Dr. Liu.
Lastly, the researchers looked for APOBEC3G’s mutational signature in a widely used human tumor DNA database, The Cancer Genome Atlas, and found that these mutations appear to be common in bladder cancers and are linked to worse outcomes.
“These findings will inform future efforts to restrict or steer tumor evolution by targeting APOBEC3 enzymes with drugs,” said Dr. Faltas.

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New biomarker test can detect Alzheimer's neurodegeneration in blood

A group of neuroscientists led by a University of Pittsburgh School of Medicine researcher developed a test to detect a novel marker of Alzheimer’s disease neurodegeneration in a blood sample. A study on their results was published today in Brain.
The biomarker, called “brain-derived tau,” or BD-tau, outperforms current blood diagnostic tests used to detect Alzheimer’s-related neurodegeneration clinically. It is specific to Alzheimer’s disease and correlates well with Alzheimer’s neurodegeneration biomarkers in the cerebrospinal fluid (CSF).
“At present, diagnosing Alzheimer’s disease requires neuroimaging,” said senior author Thomas Karikari, Ph.D., assistant professor of psychiatry at Pitt. “Those tests are expensive and take a long time to schedule, and a lot of patients, even in the U.S., don’t have access to MRI and PET scanners. Accessibility is a major issue.”
Currently, to diagnose Alzheimer’s disease, clinicians use guidelines set in 2011 by the National Institute on Aging and the Alzheimer’s Association. The guidelines, called the AT(N) Framework, require detection of three distinct components of Alzheimer’s pathology — the presence of amyloid plaques, tau tangles and neurodegeneration in the brain — either by imaging or by analyzing CSF samples.
Unfortunately, both approaches suffer from economical and practical limitations, dictating the need for development of convenient and reliable AT(N) biomarkers in blood samples, collection of which is minimally invasive and requires fewer resources. The development of simple tools detecting signs of Alzheimer’s in the blood without compromising on quality is an important step toward improved accessibility, said Karikari.
“The most important utility of blood biomarkers is to make people’s lives better and to improve clinical confidence and risk prediction in Alzheimer’s disease diagnosis,” Karikari said.

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Hong Kong to scrap almost all its Covid rules

Published21 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Kathryn ArmstrongBBC NewsHong Kong is dropping almost all its Covid restrictions this week, following a similar move by mainland China.From Thursday, people arriving in the city – a special administrative region of China – will no longer have to do mandatory PCR tests.The vaccine pass system will also be scrapped – but compulsory masks in public places will continue. It is a dramatic move by the city, which once had some of the toughest restrictions in the world. Also being scrapped from Thursday is the rule that limits the number of people allowed to gather outside to 12. This was increased from four people in October as part of measures to begin reopening the city.From September: Hong Kong to end Covid hotel quarantine policyHong Kong’s leader, John Lee, cited high vaccine rates as one of the reasons for lifting restrictions. According to government figures, 93% of the population have had two vaccine doses, while more than 83% have received three.But only 64% of people over 80 – the most vulnerable age group – have had three doses.Unlike mainland China, which has developed its own vaccines, Hong Kong has also used mRNA vaccines – including the BioNTech jab made in Germany – that have been shown to be more effective.”Hong Kong has a sufficient amount of medicine to fight Covid, and healthcare workers have gained rich experience in facing the pandemic,” Mr Lee said on Wednesday.”The society has established a relatively extensive and overall anti-epidemic barrier.”Mr Lee added that instead of the vaccine pass, which has limited access to public places for unvaccinated since it was introduced in February, the city would take “more targeted measures” – including promoting vaccination for the elderly and children. More than 11,000 people have died with Covid in Hong Kong, according to official numbers, from more than 2.5m cases.Since the pandemic began, the city has largely followed mainland China’s lead in efforts to tackle the virus, including attempts to eliminate it with a “zero-Covid” strategy. This has been criticised by some residents and business owners – who said the policy damaged Hong Kong’s economy and international standing.The scrapping of the Hong Kong’s Covid restrictions comes weeks after mainland China made a similar move following landmark protests against the strict controls. On Monday and Tuesday, Beijing announced further plans to ease travel restrictions. Hong Kong has said that it will fully reopen its borders with the rest of China before mid-January.The mainland is currently experiencing a surge in cases, with reports suggesting hospitals are overwhelmed and elderly people are dying. Hong Kong is part of China and is governed by the “one country, two systems” principle, but Beijing has tightened control in recent years.Covid and Hong Kong’s cage menThis video can not be playedTo play this video you need to enable JavaScript in your browser.More on this storyHong Kong shortens Covid hotel quarantine8 AugustChinese rush to book travel as Covid rules lifted1 day agoHow is China trying to beat its latest Covid surge?6 days agoHow is Hong Kong run?1 July

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¿Hasta qué edad hay que hacerse el papanicolau?

Hace más o menos una década, Andrea Clay se conectó a internet para leer sobre las nuevas directrices revisadas sobre el chequeo del cáncer de cuello uterino.Ninguno de sus proveedores de atención sanitaria le había mencionado que las mujeres mayores de 65 años con un riesgo promedio de cáncer de cuello uterino podían dejar de hacerse la prueba de papanicoláu si hasta entonces se habían realizado las pruebas pertinentes.Pero eso es lo que recomendaba el Grupo de Trabajo de Servicios Preventivos de Estados Unidos, según supo Clay, junto con el Colegio Estadounidense de Obstetras y Ginecólogos y la Sociedad Estadounidense del Cáncer.Enfermera y técnica de urgencias médicas en Edison, Washington, Clay se alegró en silencio. A lo largo de décadas de pruebas, nunca había tenido un resultado anormal en la prueba de papanicoláu y no pertenecía a ningún grupo de alto riesgo.“Ya no quería estar en esos estribos”, dijo. “No creo que sea necesario”. Imprimió las directrices, lista para pelearse si una enfermera o doctor le insistía en que siguiera haciéndose la prueba. Pero nadie lo hizo.Ahora, de 74 años, ya no se ha hecho exámenes para cáncer cervical en años. “Ya acabé con eso”, expresó.En cambio, JB Lockhart, de 70 años, una oficinista jubilada de Lake Oswego, Oregón, sigue programando un papanicoláu anual.El año pasado, cambió de ginecóloga-obstetra. “Me dijo que ya no tenía que hacerme la prueba”, recuerda Lockhart. “Pensé: hasta cierta edad todavía se puede contraer cáncer cervical”.Le dijo a la médica: “Prefiero estar tranquila y prevenir”.A Lockhart no la disuade el hecho de que el grupo de trabajo y los grupos médicos recomienden que se realice el cribado para el cáncer cervicouterino solo cada tres o cinco años (dependiendo de las pruebas a las que se sometan las pacientes) ni la recomendación de que las mujeres con un número determinado de resultados normales pueden dejar de hacerse la prueba a los 65 años.La calificación “D” del grupo de trabajo para el cribado del cáncer cervicouterino en mujeres mayores, la cual significa “certeza moderada o alta de que el servicio no tiene ningún beneficio neto o de que los daños superan los beneficios”, tampoco la ha hecho desistir.Muchas otras mujeres mayores siguen haciéndose pruebas de detección de este tipo de cáncer, según un estudio reciente publicado en JAMA Internal Medicine.Usando datos de Medicare para analizar a 15 millones de mujeres durante 20 años, los investigadores encontraron que la proporción que recibió al menos una prueba de papanicoláu o VPH (virus del papiloma humano) disminuyó de casi el 19 por ciento en 1999 al 8,5 por ciento en 2019, una victoria potencial para aquellos preocupados por las pruebas excesivas y el tratamiento excesivo en adultos mayores.“Esperábamos la tendencia”, dijo la autora principal del estudio, Jin Qin, investigadora de salud pública en la División de Prevención y Control del Cáncer de los Centros para el Control y la Prevención de Enfermedades. “Pero a esta escala, a este nivel, es un poco sorprendente”.Las directrices especifican que las mujeres con un riesgo promedio pueden dejar de someterse al chequeo de cáncer cervical después de los 65 años si, en los últimos 10 años, han tenido tres pruebas de papanicoláu consecutivas negativas o dos pruebas de VPH consecutivas negativas (que pueden hacerse al mismo tiempo que una papanicoláu). Las pruebas negativas más recientes deben haberse realizado en los últimos cinco años.Las mujeres que se hayan sometido a una histerectomía y no tengan lesiones precancerosas previas también pueden dejar de hacerse exámenes.Cuando se les dice que pueden dejar de hacerlo, “muchas de mis pacientes se alegran”, afirma Hunter Holt, médico de familia de la Universidad de Illinois, Chicago, y coautor del estudio. No muchas estaban deseosas de tener que desvestirse y que les introdujeran un espéculo para que un profesional de la salud raspara células del cuello uterino para analizarlas.Las mujeres con un riesgo medio de cáncer de cuello uterino pueden dejar de someterse a las pruebas de cribado a partir de los 65 años si no han dado positivo recientemente. Pero muchas mujeres se sienten incómodas al hacerlo.Tony Dejak/Associated PressAun así, más de 1,3 millones de mujeres mayores de 65 años siguieron recibiendo cribados y servicios relacionados en 2019; el 10 por ciento tenía más de 80 años, un grupo de riesgo especialmente bajo. “Con millones de pacientes, se convierte fácilmente en un costo para todos”, dijo Qin. El estudio calculó que Medicare gastó aproximadamente 83,5 millones de dólares en 2019.Entonces, ¿se está examinando de más a quienes siguen haciéndose estas pruebas? No necesariamente.“No todas las mujeres deben dejar de hacerse las pruebas a los 65 años”, señaló Sarah Feldman, ginecóloga oncóloga del Brigham and Women’s Hospital de Boston y coautora de un editorial que acompaña al estudio de Qin.Algunas mujeres se consideran de alto riesgo debido a antecedentes de cáncer cervicouterino o lesiones precancerosas o porque tienen un sistema inmunitario debilitado. Según Feldman, estas mujeres deben seguir sometiéndose a las pruebas, a veces hasta 25 años después de un resultado positivo. Las mujeres que estuvieron expuestas en el útero al fármaco dietilestilbestrol, o DES, también se consideran de alto riesgo.Otras mujeres deben seguir haciéndose pruebas de detección porque no se han sometido a suficientes pruebas previas o no están seguras de cuántas se han hecho y cuándo. Es posible que algunas no se hayan sometido a un control adecuado porque no contaban con seguro médico antes de tener derecho a Medicare y no podían pagar las pruebas.Dado que los registros de Medicare no incluían historiales médicos anteriores a los 65 años, los investigadores no pudieron determinar cuántas pruebas eran innecesarias. Pero varios estudios han revelado que muchas mujeres no se someten a las pruebas recomendadas antes de los 65 años y, por tanto, no deberían dejar de hacérselas después.Alrededor del 20 por ciento de los casos de cáncer del cuello de útero en Estados Unidos se dan en mujeres mayores de 65 años, señaló Feldman. “Es una enfermedad prevenible si se realiza un examen de diagnóstico a las personas adecuadas y se trata”, afirmó.Sin embargo, todo examen conlleva daños y beneficios. En el caso de las pruebas de detección de cáncer cervical, dijo Holt, las desventajas pueden incluir incomodidad, especialmente porque los tejidos vaginales se adelgazan con la edad y angustia emocional para las víctimas de abuso sexual.Además, “cuando vemos algo en la prueba, tenemos que responder”, dijo. “Cualquier prueba de detección que dé positivo puede provocar ansiedad, estrés y estigma”.Un resultado positivo también conlleva otros procedimientos, normalmente una biopsia en la que se utiliza un colposcopio, un instrumento de visión que amplía el cuello uterino. En ocasiones, las biopsias pueden provocar hemorragias e infecciones, y los resultados suelen mostrar que la paciente no tiene cáncer ni precáncer (aunque estos pueden desarrollarse en el futuro).También puede haber falsos positivos. Aunque los datos sobre los resultados del chequeo en mujeres mayores de 65 años son escasos, Holt y varios coautores publicaron en 2020 un estudio en el que se estimaban las tasas de falsos positivos en mujeres más jóvenes. Según su modelo, las mujeres que se someten a pruebas de detección durante 15 años a partir de los 30 años deberían hacerse una colposcopia, quizá dos, dependiendo de qué pruebas se realicen y con qué frecuencia.Entre el 60 por ciento y el 75 por ciento de esos procedimientos no encontrarían lesiones precancerosas ni cáncer, lo que indicaría que los resultados de las pruebas iniciales eran falsos positivos.Tiene sentido que las mujeres hablen con sus proveedores de atención médica sobre cuándo deben dejar de hacerse las pruebas. Las personas mayores constituyen una población diversa: las mujeres mayores de 65 años pueden tener múltiples parejas sexuales, lo que aumenta su riesgo de cáncer, por ejemplo, o quizá padezcan enfermedades graves que muy probablemente acabarían con sus vidas mucho antes de que lo hiciera el cáncer de cuello uterino.Los investigadores han observado que los adultos mayores a menudo son reacios a renunciar a las pruebas de detección del cáncer, independientemente de lo que digan las directrices.Mara Schonberg, internista del Beth Israel Deaconess Medical Center de Boston, lleva años trabajando para ayudar a las mujeres mayores a reducir las mamografías innecesarias, que el Grupo de Trabajo de Servicios Preventivos no recomienda a las mayores de 75 años, con el argumento de que no hay pruebas suficientes de su beneficio.Schonberg elaboró un folleto para explicar los pros y los contras. Reunió una muestra de 546 mujeres mayores de 75 años y descubrió que la mitad de las que recibieron el folleto estaban más informadas y eran más propensas a hablar de la mamografía con sus médicos. Además, más de la mitad de las que lo leyeron se hicieron una mamografía de todos modos. Una “ayuda para la toma de decisiones” similar no consiguió disuadir a las personas mayores de someterse a una prueba de cáncer de colon.La Sociedad de Medicina Interna General desaconseja las pruebas de detección del cáncer a los pacientes con una esperanza de vida inferior a 10 años. Pero la esperanza de vida puede ser un concepto difícil de discutir con los pacientes.Una encuesta realizada a proveedores de California que realizaban pruebas de detección del cáncer cervical en mujeres de bajo riesgo mayores de 65 años, a pesar de conocer las directrices en contra, evidenció qué es lo que dificulta que estas se pongan en práctica. El 56 por ciento de los profesionales de la salud creía que si dejaban de realizar la prueba no detectarían un caso de cáncer, pero casi el mismo número reconocía que se tardaba menos tiempo en realizar la prueba que en explicar a las pacientes por qué era innecesaria. Y el 46 por ciento señaló que las pacientes los “presionaban” para que siguieran haciéndoles la prueba.Lockhart programó una cita en febrero para su próxima prueba de papanicoláu. La persona encargada le explicó que no necesitaba otra prueba, pero Lockhart dijo que seguiría haciéndosela de todos modos.

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India Covid: Experts say people don't need to panic over China coronavirus surge

Published46 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Meryl SebastianBBC News, KochiExperts have told the BBC that the current Covid surge in China is “unlikely” to impact India, but they urged people to stay cautious and wear masks.India has stepped up surveillance after a spike in cases in neighbouring China.People travelling from China and four other Asian countries now have to produce a Covid-19 negative test report before entering India.On Tuesday, drills were held to check if hospitals could handle a surge.According to government data, India currently has only around 3,400 active coronavirus cases. But reports of the surge in China and the memories of two deadly Covid waves in 2020 and 2021 in India have made many people fearful.But experts say there is no reason to worry right now.”The infection surge in China is on expected lines. If you have a susceptible population that is not exposed to the virus, cases will rise. Nothing has changed for the rest of the world, including India,” says Dr Chandrakant Lahariya, an epidemiologist and health systems specialist. China has been struggling with a rush of Covid cases after it started moving away from its so-called zero-Covid approach which mandated strict lockdowns, quarantining and closed borders. The country is now trying to ramp up vaccinations for its vulnerable elderly population as the case surge strains healthcare systems.The surge has also led some experts raising doubts over whether the main vaccines used in China – Sinovac and Sinopharm – can provide long-term immunity.”People are getting infected because BF.7 [the Omicron subvariant that reports say is driving the surge in China] is highly infectious and escapes all previous immunity. If you don’t have immunity, you get more diseases which will affect the elderly and immunosuppressed populations,” says virologist Dr Jacob John.Over the past few months, India reported four Covid-19 cases caused by BF.7 – all the patients have recovered, health officials say.”Covid is still around, people are still getting infected and getting admitted to hospitals. So it’s not that we’re free of Covid, but it’s become like another upper respiratory tract infection, like influenza,” says epidemiologist Dr Lalit Kant.The low caseload in India can be largely attributed to the immunity Indians have already gained over the past three years.Dr A Fathahudeen, a prominent critical care expert who has treated thousands of Covid patients, says that India’s “hybrid immunity wall” against Covid-19 is “satisfactory” as a majority of people have either taken two doses of the vaccine or gained natural immunity from contracting the disease earlier.He also points out that the vaccines used in India are “more efficacious than the ones used in China”.India has administered more than 2.2 billion doses of the Covid vaccine so far, including for both doses and the booster shot, which India calls a “precaution dose”.He says people should take the booster dose if they haven’t already – only around 27% of the population have got it so far. It’s an appeal that other experts broadly agree with.”With time, the level of antibodies go down. So a third shot is always beneficial and will increase the level of antibodies,” Dr Lahariya says, adding that it’s good for people above 60 years of age.”Among the 18-59 year age group, those who are high-risk can get boosters. For others, it’s a personal call,” he adds.Experts also agree with the government’s decision to step up genome sequencing which allows scientists to identify new strains.”The current testing strategy of random genome sequencing of 2% of international travellers is enough to pick up any new variant,” says Dr Fathahudeen.Dr John says that the best mantra for the government and ordinary people to follow is “expect the best and prepare for the worst”.”Make it a habit to wear masks in crowded places – watching a football or cricket match, or on a crowded bus or train,” he says, adding that he recommends creating “long-term, sustainable behavioural changes”.India had relaxed its mask-wearing rules earlier this year after a drop in infection levels, and it’s now common to see people in crowded areas without any precautions.The bottom-line is “be cautious, wear a mask and watch the news”, Dr John says. Dr Fathahudeen agrees, saying unnecessary crowding should be discouraged and people should wear masks if large gatherings can’t be avoided. Read more India stories from the BBC:The indie music stars knocking Bollywood off the chartsIndian man killed over daughter’s viral videoThe sweet story of India’s ‘first’ Christmas cakeIndia’s Modi urges caution amid China Covid surgeAnxious Christmas for families of Indians held in NigeriaWhat it will mean when Indians outnumber ChineseYou might also be interested in:This video can not be playedTo play this video you need to enable JavaScript in your browser.More on this storyIndians told to mask up amid China Covid surge5 days agoThe ‘unknown’ Covid deaths in rural India. Video, 00:06:46The ‘unknown’ Covid deaths in rural India8 June 20216:46Patients die without oxygen amid Delhi Covid surge25 April 2021

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‘I went through the menopause before my mum did’

Published16 minutes agoShareclose panelShare pageCopy linkAbout sharingBy Deirdre Finnerty, Elise Wicker and Yazmina GarciaBBC NewsImagine you’re in your teens or 20s and you find out you’re already in menopause. It wasn’t how Emma, Soe-Myat and Elspeth had pictured their early adulthood. Their diagnosis was the start of a lonely journey to learn about a life event all women will experience with age but rarely talk about. It was a sticky August morning in 2013 when a consultant flicked through Emma Delaney’s medical file and told her she was menopausal at 25. Emma sat motionless in the hard hospital chair, her mind drifting in and out of what he was saying. Her periods, which hadn’t returned since she had come off the pill a few years before, probably never would. It was unlikely she’d ever be able to conceive naturally. “I didn’t know how to react… He told me like I’d lost my keys that I couldn’t have children,” she says. Emma is part of a group of women affected by a condition called Primary Ovarian Insufficiency (POI) – which refers to any form of menopause under the age of 40. Most of the time there is no known cause and women with POI can experience menopausal symptoms until they’re in their 50s. Around one in 100 women in the UK are affected by the condition and experts believe it could be more common than that. But it’s an issue that remains under-discussed. What is the menopause and what are the signs?”There isn’t enough conversation about menopause in the younger age groups at all,” says Dr Nighat Arif, an NHS GP and TikTok star with a specialist interest in menopause care. “Typically, you see an older woman, white, grey-haired, wafting a fan. It’s not representative.” For some like Emma, it’s not clear why their ovaries aren’t functioning, but POI can also be caused by auto-immune conditions, chromosomal disorders or surgery to the womb or ovaries. As well as the physical consequences, the psychological impact of such a diagnosis can be devastating. After Emma’s doctor broke the news to her, she cried by herself in her car for an hour. Emma knew next to nothing about menopause, except what she’d heard from older women in the busy Manchester hair salon that she worked in. The future she’d imagined – looking after two children of her own – had been taken away.Over the next few months, Emma was put on Hormone Replacement Therapy (HRT) tablets. She learned that her ovaries had stopped functioning and her body didn’t produce enough oestrogen and progesterone – the hormones that govern the menstrual cycle. The imbalance had been affecting her health for years.HRT explained: Is it right for me? The brain fog she kept experiencing wasn’t just part of her personality, she realised. Hot flushes, which felt like a firework shooting through her whole body, hadn’t been caused by long hours with hairdryers. And her sleepless nights weren’t down to insomnia – they were another symptom of the hormone imbalance.It didn’t help that her own mother, then only in her early 40s, hadn’t yet reached the menopause. Her friends were starting to settle down and have children of their own. “It felt like no-one understood me,” she says. Emma threw herself into work and avoided discussing her diagnosis. She filled her evenings with big nights out and casual dates – she wanted to be exactly the opposite of her friends with partners and babies. “I abused my body with alcohol and sex… I didn’t realise how much I needed to talk about it to someone,” she explains. If going through the menopause prematurely were not hard enough, for a growing number of women the diagnosis comes after they have begun treatment for other serious conditions.For London graphic design student Soe-Myat Noe, menopause came as an unexpected consequence of cancer treatment. Earlier this year, aged just 23, she was diagnosed with stage three bowel cancer. Radiation in her pelvic area damaged her ovaries but at the time, she didn’t understand what this would mean. “They [doctors and nurses] were solely focussing on my cancer and my cancer treatment… I don’t think anyone mentioned to me what the menopause entailed,” she says. Her symptoms – which included ringing in her ears, anxiety, fatigue – came on suddenly, and were severe. Conversations about periods, fertility and menopause weren’t common when Soe-Myat was growing up, so she hadn’t learned what to expect. Her university friends, concerned about IUDs and the contraceptive pill, couldn’t relate to her experience. “Everything that was happening to me, I always associated with older people… I felt like I skipped a whole chunk of my life.” While Soe-Myat could talk about her mental health with a therapist, her physical menopause symptoms hadn’t been considered. She had to advocate for herself, googling treatments while exhausted from chemotherapy and dealing with a stoma bag.Although HRT can be unsuitable for women with certain types of cancer, there was a form that was safe for Soe-Myat, and once she began taking it her symptoms improved. Since then, she has been given the all-clear. As well as continuing with HRT, she does non-medical things like going for walks and avoiding hot drinks to help herself. But she wishes that she had been given advice about managing her symptoms earlier in the process. “It shouldn’t be that difficult”, she says. Dr Nighat Arif’s social media accounts are full of messages from women who have had similar experiences. She calls for a “better understanding of the nuances” of menopause care among healthcare professionals and wants women of all ages to “break the taboo” around it. “Please talk to the women in your life… have that conversation with your mum, your grandma, your aunts, your cousins, your best mate. It’s nothing to be embarrassed about – learn from what they’re going through.”Dr Arif says more women are now being diagnosed with POI because of a greater awareness of symptoms, but it can still take a long time to get a diagnosis. And left untreated, POI can have long-term consequences for women’s bones, hearts and mental health. “Some patients can find themselves in a very dark place,” she says. “They might have wanted to have children and it scuppers the life choices they thought they could make.” In her surgery, Dr Arif also sees other, rarely discussed consequences of POI – like painful sex and loss of libido. Elspeth Wilson, 23, understands this all too well. Diagnosed with POI when she was just 15, difficulty with sex is an obstacle she has navigated throughout her whole dating life. “It’s so hard to be in a relationship with someone and want to show that you love them. But your body is just not agreeing with it and certain things are uncomfortable,” she says. “What frustrates me is that the doctors never said that this could be an issue.”Elspeth has just started her first job after university, as a market-researcher in Newcastle. Though she praises her employer for being supportive, navigating this big transition with POI can be tricky. “It adds to the imposter syndrome. I’ll have moments where I’ll have brain fog, and it will kick in at the absolute worst time.”She’s found comfort in a WhatsApp group of other women in a similar situation. In their group chat, nothing is off-limits. “It’s reassuring to just have that space to ask those questions and vent… If you have the ability to talk about it in a way where you have no ounce of shame, it’s way easier.” Soe-Myat, who joined an online support group for young women with cancer-induced menopause agrees. “I felt validated”, she says.It is a lesson that Emma, too, has learned over time.After years of trying to block out the pain of her diagnosis, Emma eventually began to speak about her experiences more openly. She started by explaining her feelings to a counsellor, who helped her feel more like herself again. “No matter my diagnosis, I was still me… I was more than my diagnosis… That was a big lesson to learn.” A few years ago, she met a partner who understands her condition, and they now live together. On Instagram, she followed hashtags to do with menopause and found the Daisy Network, a charity set up to offer information and support to women with POI. For the first time, she spoke to other people who understood what she was going through.Now 34, she thinks her future may include children. Egg-donation and IVF would be too upsetting, she says, so she’s considering fostering in the next few years. And every once in a while she’ll wear a black T-shirt to the salon, with the slogan “Make Menopause Matter” written across the chest in red. It’s covered in stains from being splattered with bleach. Her clients will comment that she’s too young for menopause, and she’ll explain her situation as she touches up their roots.”They tell me that they’ve learned more about menopause in the 30 minutes that they’ve spent with me than in their whole lives.”It makes me proud that I’m getting the word out there for every woman.” Menopause and me: Too young to feel so oldLots of women don’t think about the menopause until they’re in their 40s. But it could start much earlier. Emma, Soe-Myat, Olivia and Elspeth share their experiences to help others cope with menopause at any age.Watch now on BBC iPlayer (UK Only)More on this storyHRT explained: Is it right for me?8 SeptemberWhat is the menopause and what are the signs?18 OctoberRelated Internet LinksCharity for Women with POI – The Daisy NetworkTrekstockThe BBC is not responsible for the content of external sites.

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Wafer-thin device has potential to transform the field of islet cell transplantation

A quarter-sized device created at Houston Methodist could drastically alter the course of treatment for Type 1 diabetes, a chronic condition that impacts millions of Americans and does not have a cure.
In a study published in the Dec. 26 issue of Nature Communications, a research team led by Houston Methodist delivered islet cells and immunotherapy directly into a 3D printed device akin to a bioengineered pancreas, called the NICHE. The treatment restored healthy glucose levels and eliminated Type 1 diabetes symptoms in animal models for more than 150 days while avoiding severe adverse effects of anti-rejection therapy by administering immunosuppressive drugs only where the transplanted islet cells were located.
Type 1 diabetes is caused by an autoimmune reaction that destroys the cells in the pancreas that make insulin. It can also cause kidney failure. Daily insulin injections are the most conventional treatment but attaining tight control of glucose levels remains challenging and cumbersome for patients. Further, in more severe cases, patients may need pancreas and kidney transplants, or they may qualify for an islet cell transplant, where the islet cells of a deceased pancreas donor are harvested, processed and then transplanted into the Type 1 diabetes patient’s liver.
These transplants can help improve a patient’s symptoms; however, as with all organ transplants, one of the biggest challenges is the need for immunosuppressive drugs for the rest of their lives to avoid transplant rejection. Lifelong immunosuppression can lead to patients being vulnerable to infectious diseases and increases the risk of certain types of cancer.
The NICHE, created in the Department of Nanomedicine at Houston Methodist Research Institute, is a flat device placed under the skin comprised of a cell reservoir for the islets and a surrounding drug reservoir for localized immunosuppression therapy. It is the first platform to combine direct vascularization and local immunosuppression into a single, implantable device for allogeneic islet transplantation and long-term Type 1 diabetes management. Direct vascularization is fundamental for supplying nutrients and oxygen for maintaining the viability of transplanted islet cells.
“A key result of our research is that local immunosuppression for cell transplantation is effective,” said Alessandro Grattoni, Ph.D., corresponding author and chair of the Department of Nanomedicine at Houston Methodist Research Institute. “This device could change the paradigm of how patients are managed and can have massive impact on treatment efficacy and improvement of patients’ quality of life.”
The NICHE incorporates ports for the refilling of drugs as needed. The researchers refilled the drug reservoirs every 28 days, which is comparable to other long-acting drugs clinically available for migraine prevention or HIV treatment.
Grattoni’s team is working on scaling up the NICHE technology for clinical deployment, for which drug refilling may only be needed once every six months. The ability to refill the NICHE technology allows for long-term use in patients. Further, changes in drug formulations or concentration could extend refill intervals to once each year, aligning with routine physician visits.
Grattoni and his collaborators will expand this research over the next few years, with the end goal of testing the NICHE’s safety in humans in about three years. Grattoni’s nanomedicine lab at Houston Methodist focuses on implantable nanofluidics-based platforms for controlled and long-term drug delivery and cell transplantation to treat chronic diseases.
Grattoni’s collaborators on this study include Jesus Paez-Mayorga, Jocelyn Nikita Campa-Carranza, Simone Capuani, Nathanael Hernandez, Hsuan-Chen Liu, Corrine Ying Xuan Chua, Fernanda Paola Pons-Faudoa, Gulsah Malgir, Bella Alvarez, Jean A. Niles, Lissenya B. Argueta, Xian C. Li, Joan E. Nichols and A. Osama Gaber (Houston Methodist); Kathryn A. Shelton, Sarah Kezar and Pramod N. Nehete (MD Anderson Cancer Center); and Dora M. Berman, Melissa A. Willman, Camillo Ricordi and Norma S. Kenyon (University of Miami).
This research received funding support from Juvenile Diabetes Research Foundation (1-INO-2018-595-A-N), Vivian L. Smith Foundation, Houston Methodist Research Institute, Diabetes Research Institute and the National Institutes of Health (NIDDK R01DK132104).
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Materials provided by Houston Methodist. Note: Content may be edited for style and length.

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Parents Often Bring Children to Psychiatric E.R.s to Subdue Them, Study Finds

Many parents bring children to emergency rooms to manage aggressive behaviors. But the visits offer little long-term benefit, doctors said.For emergency room doctors, they are a dispiriting and familiar sight: Children who return again and again in the grip of mental health crises, brought in by caregivers who are frightened or overwhelmed.Much has been written about the surge in pediatric mental health emergency visits in recent years, as rates of depression and suicidal behavior among teens surged. Patients often spend days or weeks in exam rooms waiting for a rare psychiatric bed to open up, sharply reducing hospital capacity.But a large study published on Tuesday found a surprising trend among adolescents who repeatedly visited the hospital. The patients most likely to reappear in emergency rooms were not patients who harmed themselves, but rather those whose agitation and aggressive behavior proved too much for their caregivers to manage.In many cases, repeat visitors had previously received sedatives or other drugs to restrain them when their behavior became disruptive.“Families come in with their children who have severe behavioral problems, and the families really just are at their wit’s end, you know,” said Dr. Anna M. Cushing, a pediatric emergency room physician at Children’s Hospital Los Angeles and one of the authors of the study. “Their child’s behavior may be a danger to themselves, but also to the parents, to the other children in the home.”The findings, published in the journal JAMA Pediatrics, analyzed more than 308,000 mental health visits at 38 hospitals between 2015 and 2020.Compared with patients presenting with suicidal or self-harming behavior, those with psychotic disorders were 42 percent more likely to revisit the emergency department within six months, the study found; patients with impulse control disorders were 36 percent more likely; and patients with disorders like autism and A.D.H.D. were 22 percent more likely. Patients who required medications to subdue them were 22 percent more likely to revisit than patients who did not.Tips for Parents to Help Their Struggling TeensCard 1 of 6Are you concerned for your teen?

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