PENICILLIN PRODUCTION

BY DAKSHITA NAITHANI

Penicillin, which is now an essential element of our antibacterial arsenal had a huge influence on the twentieth century’s second half. Deep-fermentation techniques, which were established largely for the synthesis of Penicillin during WWII, paved the way for the creation of medications and aided the emergence of the young biotechnology sector in the 1970s. In the presence of blood, pus, and bodily fluids, it is effective against some gram-positive bacteria. It is soluble in water, acetone, ethyl alcohol, and ether, but less so in benzene, chloroform, and other organic solvents.

 It is a secondary metabolite, like other antimicrobials, and is only generated in the stationary phase. The industrial manufacturing may be divided into two processes: upstream and downstream.

When the development of the fungus is hindered by stress, it produces certain species of Penicillium. Penicillin production is likewise restricted by feedback in the synthesis process.

α-ketoglutarate + AcCoA → homocitrate → L-α-aminoadipic acid → L-lysine + β-lactam

Because the by-product L-lysine hinders homocitrate synthesis, exogenous lysine should be avoided in its manufacture.

The cells are cultivated using a process known as fed-batch culture, in which the cells are continually exposed to strain, which is necessary for inducing its synthesis. It’s also crucial to consider the carbon sources available: glucose inhibits its synthesis, but lactose does not. The pH of the phases, as well as the amounts of nitrogen, lysine, phosphate, and oxygen, must all be monitored closely.

THE FERMENTATION PROCESS

INOCULUM: The source of inoculum is master stock (spores). They are cultivated working samples are immersed in water and mixed with wheat bran and nutrition solution in a flask. A four-day-old shaking flask culture is inoculated into a seed tank for three days.

THE MEDIUM: In 1958, Jackson created a medium for the manufacture of penicillin. Fermentable carbohydrate (corn steep liquor (3.5%), organic nitrogen source, lactose (3.5%), glucose (1%), potassium di-hydrogen phosphate (0.4%), calcium carbonate (as a buffer) (1%),  phenyl acetic acid precursor, edible oil (0.25%), pH near 6.

As temperature is very important aspect during its production it should be around 280 degree Celsius and the supply of oxygen in the bioreactor acts as a limiting factor in its production the aeration speed should be between 3.0-1.5.

Fermentation is the method through which Penicillin is commercially produced. It’s a fed-batch technique performed in aseptic conditions in stainless steel tank reactors with capacities ranging from 30 to 100 thousand gallons. The fermentation process consists of two to three seed development phases, followed by a fermentation production phase that lasts 120 to 200 hours. For this procedure, a variety of carbon sources have been used. During the active Penicillin synthesis phase, sugar is also utilised to regulate the pH value.

During fermentation, mini-harvest techniques are commonly used. They entail removing 20-40 percent of the overall of the fermenter’s contents and replacing it with new sterile medium. This method can be done multiple times during the process without lowering the overall Penicillin yield per fermenter; in fact, it can increase it.

Penicillin is discharged into the fermentation medium and collected at the end. With a 2-5 percent increase in total extraction efficiency, whole broth extraction is best conducted at an acidic pH. Amyl, butyl, or isobutyl acetate is used to extract cooled acidified broth from a solvent.

These fermentations are extremely mechanised and computerised in today’s world. For optimum antibiotic synthesis, all essential precursors, such as ammonia, sugar, carbon dioxide, and oxygen, are carefully monitored, along with temperature and pH. During the active manufacturing phase, the pH should be between 6.4-6.8.

PURSUIT FOR A BETTER YIELD

Penicillin was first produced using the fungus Penicillium notatum toward the conclusion of World War II, yielding one milligramme per cubic decimeter. Today’s yield is 50 grammes per cubic decimeter, thanks to the use of a new species (Penicillium chrysogenum) and better extraction techniques.

These yields can be increased further by improving the medium’s composition, isolating the above- mentioned Penicillium chrysogenum, which grows better in large deep fermentation tanks, and developing a submerged culture technique for mould cultivation in large volumes of liquid medium through which sterile air is forced.

Its manufacturing has remained mostly reliant on traditional strain improvement. The most important occurrences in high-yielding Penicillium chrysogenum strains are the expansion of the Penicillin biosynthetic gene cluster between tandem repeats. There have also been created molecular methods that are not based on increasing biosynthetic gene dosages.

 THE EARLY PRODUCTION OF PENICILLIN

The consortium of British and American experts came together to enhance manufacturing processes and their initial objective was to find the strains of Penicillium chrysogenum that generated the most penicillin. They quickly discovered that a Penicillium chrysogenum strain acquired from a mouldy cantaloupe at a Peoria local farmers market produced greater amounts of Penicillin than those recently tested. Scientists utilised x-rays and ultraviolet light to produce even more mutants from the farmer’s market strain.

Following those experiments, it was discovered that growing Penicillium in immersed culture media rather than on a plate surface enhanced growing efficiency, and that changing the nutrient base from sucrose to lactose or corn-steep liquor (a nutrient-rich by-product of corn processing) also increased yield. 

MODERN PRODUCTION METHODS

Major advances in contemporary manufacturing processes have improved output while lowering costs. Nowadays, commercial generating strains of Penicillium chrysogenum are produced utilising submerged culture in 50,000-gallon stainless steel tanks that are continually agitated and aerated. With a 90 percent recovery rate, these commercial strains can now produce 40-50 gram of Penicillin per litre of culture. This is a huge leap forward over the first Peoria farmer’s market strain, which only produced 0.15 grams per litre and had extremely low recovery rates.

Amplification of the biosynthesis gene cluster, an increasing amount of peroxisomes, and increased levels of transporter proteins that secrete newly production out of the peroxisomes and the cell are among the genetic and cellular modifications that result in increased production in modern Penicillium strains.

Penicillin related antibiotics now generate more than $15 billion in annual sales worldwide. Despite the fact that costs are at an all-time minimum, these sales figures exist. Penicillin currently costs $10 per kilogramme, compared to $300 in 1953. Though Europe is the world’s largest manufacturer of beta-lactam antibiotics, newer production facilities are moving to China and other Asian countries with reduced labour and energy prices.

Hyperthyroidism Awareness

It is important to remember that hyperthyroidism can occur at any age. While most may present with a rather typical constellation of symptoms, many may present with exacerbation of pre-existing conditions which may make the diagnosis initially elusive. Worsening anxiety, insomnia, fatigue, panic attacks, palpitations, hypertension or diarrhea may not initially signal that the thyroid is involved. Clinicians must have a low threshold to check thyroid function early to rule out a component of hyperthyroidism.

Once a suppressed thyrotropin (TSH) has been detected, further investigation with serum triiodothyronine (T3) and free thyroxine (free T4) can help delineate overt from subclinical disease. A thorough history of past thyroid disease, as well as current medications and supplements, can help detect any pre-existing diagnoses or exogenous sources of thyroid hormone or over supplementation with iodine. More commonly, hyperthyroidism is due to either Graves diseasetoxic multinodular goiter or toxic adenoma. Distinction between these can usually be made with the assistance of a thyroid uptake scan, TSH receptor antibody measurement, and thyroid ultrasound. An additional physical exam finding of exophthalmos can further support the diagnosis of Graves’ disease. Understanding the etiology can help guide patient expectations. A small percentage of patients with Graves’ Disease may undergo spontaneous remission after 1 to 2 years, which may prompt patients to wait before considering a definitive treatment option.

With confirmation of the diagnosis of hyperthyroidism, focus is on hormonal control with an antithyroid medication (ATM, most commonly Methimazole in the United States). This may be augmented with beta-blockade, steroids, cholestyramine or SSKI for those who are difficult to control.

Many patients may need further consideration for definitive management with either radioactive iodine ablation (RAI) or thyroidectomy. Your local resources may also influence these options, but it is critical to understand that all three treatments (ATM, RAI and thyroidectomy) are possible options. Certain patient factors and priorities may alter the preferred definitive treatment. Smaller gland size, easy to control hormones, and lack of eye symptoms are factors that may favor continued ATM management. A large goiter with compressive symptoms, difficult to control hormones requiring high dose medications/ multiple modalities, pregnancy, severe eye disease, multiple nodules within the thyroid with or without thyroid cancer, or desire for rapid and reliable hormone control may favor thyroidectomy. RAI is a good option for patients with a smaller gland size, and a desire to pursue definitive management but avoid surgery.

There are also relative contraindications for treatment options. ATMs may have serious side effects, like agranulocytosis or liver failure, which prevent further use, or may cause skin eruptions making long term use intolerable. Additionally, high dose requirements or fluctuating doses may make long term use of ATMs not reliable. Women who are pregnant, wanting to become pregnant in the next 6 months to 1 year, breast feeding or have small children in the home will want to avoid RAI. Patients with severe eye involvement, have a large goiter with compressive symptoms, or are smokers should also avoid RAI. Thyroidectomy will be a poor option for patients with multiple previous neck operations on or around the thyroid due to internal scarring, or who are high risk for general anesthesia. Additionally, if they have a history of previous gastric bypass surgery, they are higher risk for major complications from hypocalcemia/hypoparathyroidism after thyroidectomy.

To help the patient navigate these decisions, it is important to allow them the opportunity to discuss each treatment option with respective physician experts – medical management with endocrinology, RAI with endocrinology and potentially nuclear medicine as well, and thyroidectomy with the thyroid surgeon.

In summary, patients with hyperthyroidism require medical control, as well as a clear understanding of the etiology of their hyperthyroidism. Patients with Graves disease, toxic multinodular goiter and toxic adenoma have more than one treatment option, and it is important for patients to be educated and engaged in treatment decisions.

For Further Reference:
American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and other causes of Thyrotoxicosis| by the American Thyroid Association

What Kind of Introvert Are You?

Are you an introvert? It depends on which book you read. Here’s a sampling of the various conceptualizations of introversion in pop culture [1]: Preference for quiet, minimally stimulating environments: Quiet by Susan Cain Preference for concentration and solitude: The Introvert’s Way by Sophia Dembling Rechargeable battery: The Introvert Advantage by Marti Olsen Laney Thoughtful-introspective

Are you an introvert? It depends on which book you read.

Here’s a sampling of the various conceptualizations of introversion in pop culture [1]:

Historically, there has been just as much confusion in the psychological literature. Carl Jung originally defined introversion as a focus on one’s “inwardly directed psychic energy”. However, in the 30s, the psychologist J.P. Guilford showed that various attempts to measure Jung’s conceptualization of introversion resulted in multiple, distinct factors. In other words, there didn’t appear to be a single dimension of personality that captured all of introversion.

In the 60s Patricia Carrigan echoed this point, arguing that introversion was not effectively captured by a single scale. She cautioned that if the phrase introversion is to continue to be used, “care must be taken to specify its conceptual and operational referent. What appear to be minor distinctions between the various conceptions may in fact be crucial ones.” In the 70s, the heated debate continued, with a much older Guilford arguing with H.J. Eysenck over whether introversion can possibly, or even should, be captured by a single scale.

All seemed to be settled in the 90s with the emergence of the “Big Five” framework of personality. The five main factors of personality– extraversion, neuroticism, agreeableness, conscientiousness, and intellect/imagination– were empirically derived based on what patterns of behavior tend to go together within individuals. Under this framework, introversion is merely defined as the opposite of extraversion.

In the Big Five framework, extraversion comprises two main aspectsenthusiasm (reflecting sociability, positive emotions, and warmth) and assertiveness (reflecting the tendency to take charge, become a leader, and captivate attention). The common factor seems to be high sensitivity to rewards in the environment— which due to the highly social nature of humans throughout the course of human evolution, most prominently consists of rewards associated with social attention.

Therefore, under the dominant personality framework in modern psychology, if you score low in enthusiasm and assertiveness, you’re an introvert

Here’s the problem: the Big Five framework forces a definition of introversion onto people, many of whom do not conceptualize introversion in the same way. For instance, one study did a comparison of common-sense/everyday notions of introversion and ‘scientific’ conceptions of introversion. They found that the most prototypical characteristic of introversion, as identified by the general public, was the following item:

Clearly, many people equate introversion with introspection. In the Big Five framework, however, this item is classified as part of the intellect/imagination domain of personality, not the introversion domain. So there’s a serious mismatch between folk definitions of introversion and scientific definitions. People who view themselves as introverted because they are highly introspective are being told by scientists: “You aren’t really introverted based on patterns of covariation among the general population.” To which everyday people rightfully respond: “WTF?” [3]

As noted personality psychologist Jonathan Cheek told me, “by invalidating the ordinary language meaning of introversion by defining it solely as the opposite of Big Five Extraversion, the Big Five researchers are guilty of Psychological Imperialism [4].” Influenced by the seminal work of Jung, Guilford, and Carrigan, Cheek and his colleagues have decided to take a different approach, by focusing on the phenomenon of introversion on its own, free from having to be force-fit into one scheme or another.

As Carl Jung said, each individual is ultimately a unique crystal, but type theories can be helpful for navigating social life. Embracing this Jungian philosophy, Cheek and his colleagues argue that when people use the term “introversion”, they should never just use it by itself. Instead, they argue that researchers should put a specific modifier in front of the term. What modifiers could be used?

In her masters thesis (written under the advisement of Cheek), Jennifer Odessa Grimes defined four meanings of introversion: social, thinking, anxious, and restrained (which happens to form the positive acronym STAR). It’s possible to score high or low on either of these flavors of introversion. For instance, you could be low in social introversion by preference but not be particularly anxious in the presence of people. Or you could suffer from crippling social anxiety, but still have the desire to be highly social. Or any other combination of these four meanings of introversion.

By this point you’re probably wondering what kind of introvert you are. Well, you’re in luck. There’s a new test for that.

The Case for a New Avenger

S.H.I.E.L.D. might have missed assembling team members from India, but it is never too late to correct an oversight. Imagine our larger-than-life superhero, Rajinikanth, partnering with other Avengers in a combined mission to save the planet from dangerous predators with bad intentions. Some aliens, some familiar ones! Yes, India is far from America, and the distance seems to have increased during the pandemic, but Rajinikanth could give some worthy company to Iron Man and perhaps teach him a trick or two, too, through holographic interfaces and augmented reality. Who knows, he could also kill all the mutants of Coronaviruses in this quest!

I wish to present some facts now to give you a background of my strategic human resource and leadership plan for S.H.I.E.L.D. India has one of the largest numbers of gig workers in the world. As per a March 2021 report by consulting firm Boston Consulting Group (BCG) and Michael & Susan Dell Foundation, the gig economy in India is expected to soar to 90 million in approximately a decade from now. Choose any vocation here and you will be spoilt for choices. Almost everyone is an expert on politics, economics, socio-cultural issues, fashion, sports, career, marriage, children, nature, animals, traffic, the dos, and don’ts … the list is endless. People can even advice others on how they should lead their lives. It’s affection, silly!

War for talent? Clearly, recruiters have not been able to explore the depth of this vast pool. To reiterate, India is a land bubbling with high potentials. Now let us go back to the topic of superpowers. There is plan B too. Rajinikanth could have a serious competition in a plain-looking community here. S.H.I.E.L.D. could consider appointing some members from this fraternity too.

You are rolling your eyes? Why? Hear me out. Presenting to you the case of beholders of the mighty pen (over a sword or a gun), and the upholders of fine speech. Their words hit no less than the missiles unleashed by Israel over the Gaza strip. Let me walk you through the innate gifts of a less publicized community with an immensely amoeba-like (plasma membrane) flexibility.

The teachers.

The extremely sturdy ones can stand the whole day, operate (teach) without a table and a chair, or, the basic infrastructure, and sometimes work even at low or no salaries for months. The strengths, struggles and coping mechanism of the privileged ones out of this lot are embedded in different realms. More on that, later! You will be astonished to learn how many hats teachers can don at the same time. They juggle between being a mentor, coach, counsellor, Devil’s advocate, friend, philosopher, or guide. Interestingly, even their DNA personifies versatility. Over the years, the mutations in their genetic material have helped them learn how to make milestones of the stones thrown at them by students unhappy with their marks, and parents unhappy with the teachers for giving those marks! Talk about heightened senses, their eyes can easily observe and sense the intention behind each greeting, smile and calls to the office. They are like Sharma ji ka beta/beti’, always expected to excel at everything and set an ideal example for the others to emulate.

Here, I would take a detour and ask you to recall the violinists who continued to play music for as long as they were alive, just to calm the passengers on the sinking Titanic ship. On similar lines, teachers continued to teach while the pandemic unleashed havoc around the world. The unlearning of years of classroom teaching was replaced by the immediate need to adopt new technological tools and re-learn the art of virtual teaching. The new and changed landscape was no less than the one post Thanos snapping his finger.

Aren’t convinced yet? Go to the polling booths and follow the polio immunization drives, you will know what I mean.

Now the final hook. Except for some teachers working with elite institutions, the rest won’t even charge much for their services. You can simply smile, appreciate their work, show some respect, and boy, see how they melt! Just watch how it lights up their faces. They are so motivated, especially on September 5 every year in India, that even Abraham Maslow bows to them from time to time from his grave. Had told you about their genetic sequencing earlier, remember? I do hope I have presented their (our) case well, S.H.I.E.L.D. Hopefully, you will have a relook at your current team now.

On a sidenote, can I be a contender too? Just saying. I can take it up as a gig assignment during the semester breaks. Imagine the newest Avenger on the block and that too a female from India! It will further boost the diversity and inclusion factors for you. If you can give equitable salary and perks, you could even find yourself on the pages of Harvard cases.

You might want to provide supplements of Vitamin T(eacher) to your team if Rajinikanth’s diary of appointments is full. Professor Hulk would not mind some more erudite company. In return, I vow to start quoting your example in my classes as a great employer brand with an excellent employee value proposition. Who knows, I might even write a research article. Told you, pen and words are the weapons here. Think about it. What say? Are you game?

P.S. I have recently bought a telescope to keep an eye on the stars and planets too. Taking my possible future role tad too seriously, eh?

Be kind to everyone

It is humbling to think that I have so much to give, when the truth is I have so much more to learn.

One of the most important things I’ve learned is that each and every one of us can change the world!

It’s not results that soothe our souls; it’s actions. In a difficult world, kindness has amazing power.

Every day people endure stressful jobs, demanding relationships, and backbreaking responsibility. Every day people battle life threatening disease, face uncertain futures, and struggle to survive.

Each moment of our lives, someone, somewhere, is in need of kindness.

What you do for others energizes the universe. What you do for the universe energizes you.

Go slowly. Breathe, smile, and be present. Seek opportunities to make a difference, embrace the moments, and be grateful for every choice you make.

Breathe.

Opportunities for relaxing meditation exist in every episode of your life.

One that I particularly enjoy is strolling through a bustling airport. Always surrounded by a whirlwind of activity I become entranced in a guessing game of intentions. Where have travelers been? Where are they going? Are they smiling or crying, bundled up or in flip flops? Conquering the world, or leaving the world behind?

One can choose to be engulfed by the mayhem, or detached, able to savor each moment.

Smile when you check in, even if the person behind the counter has obviously had a bad day. Help someone stow their carry-on luggage, even if it takes the space you had spotted for your own.

Accept a delay as a chance to slow down, even if it means missing a connection. I doubt that pilots and flight attendants enjoy delays any more than passengers, and life will continue on its merry way with or without us.

My favorite moment is when the aircraft door closes. The past disappears and the future becomes real. I sit back, relax, and as the jet engines spool up, close my eyes and welcome the vibrations of another new journey.

Smile at everyone you meet.

A smile is a miracle worker.

It makes us more attractive and can change our mood. No one can deny that smiling is contagious. Many have written that smiling relieves stress, boosts your immune system, and releases endorphins and serotonin. A smile can light up your face and make you look younger. A smile is a gift that we receive only by giving to others!

The greatest gift of a smile is that it keeps nothing for itself. Its purpose is to give, to console, to inspire, to cherish, to love, to multiply. Give yours freely to others. Spread happiness and feel it grow inside you. Be contagious.

Your smile brings light to the world. Would you deny the world moments of brightness?

Share your thoughts.

My thoughts are my own, and unsolicited.

Contribute to Tiny Buddha and other sites that inspire your spirit.

Submit your best effort at expressing your thoughts. Post a comment on the efforts of others. Why wait until there’s a free book giveaway to share a few words? The world wants to hear what you have to say.

As I’m sure you’ve read here many times, blog posts can arrive at just the right moment in a person’s life. Send your thoughts on their way. Someone may welcome them with open arms.

It takes courage to put your thoughts out there. Be courageous. It only takes a few moments.

Practice compassion.

Many years ago my niece died of cancer at the age of twenty-one. She was an adventurous spirit, confident and vocal. I spent many afternoons and evenings with her hand in mine as she rested uncomfortably. Her facial expressions unmasked the pain that spread within her dying body.

On better days she would tell me how she loved her visits with other patients, most of them much younger than her. These same young children I passed in the hallways, brave young children wheeling their life support beside them, and almost always smiling. I have no doubt that my niece helped create a few of those smiles.

As we all know, cancer spreads far beyond the children’s hospital that lovingly cared for my niece. We can make a difference in the lives of others by sharing our time and compassion.

Jacque’s favorite expression was “cool beans!” I don’t hear it often, but when I do, it’s like turning my gaze toward the sunshine.

Feed the hungry.

like to eat, and I would wager that you do too!

I was raised on meat and potatoes with sit-down family dinners, and never wanted for food on the table. I miss my mother’s cooking and the early evening conversations.

What I’ve never had to do is stand on a street corner and beg for food, dig through restaurant trash bins, or go to bed hungry.

Unfortunately, in today’s world, hunger touches every community.

Every community also has a food bank. It’s very easy to volunteer, and many who are hungry will benefit from your actions.

Live a giving life.

Life becomes complicated when its difficulties overpower our capacity to love others, to share our compassion, and to simply find time in our busy schedules to live a giving life.

Make a difference! Give to receive! Reap what you sow!

No matter what situation you find yourself in, come from a place of kindness and you will always treat others in the way they’re meant to be treated.

Let go of complicated. Choose simple. Make

Feeling alone

LONELINESS is packed with feelings and emotions. It can consume you at any time – day or night – and create havoc with your emotions. Feeling lonely can cause you to lose perspective and, sometimes, to lose all hope. Even before COVID, we lived in an isolated culture where people were starved for connection. And now with the fear of COVID, loneliness is even more intensified.

There are days when my life is filled with the sound of voices on the phone, or pictures of friends on Zoom and Facetime, and yet, I feel alone. There have been times in my life when I would walk in a church filled with people, or show up at a party where I knew everyone, and yet, I felt alone. At some point, we’ve all experienced feelings of being alone and the shadow of loneliness that follows close behind.

Being alone isn’t a bad thing. It’s a good, necessary, healthy thing. It’s a time to reflect, to appreciate, to think, to create, to process your life. Reflection and synthesis of ideas is crucial to learning and growing, and for many people this can only be done when they are alone. Kierkegaard nails this with one of my favorite quotes: “Life can only be understood backwards, but it must be lived forwards.” Damn, Kierkegaard, I bet you spent a ton of time alone.

So why are we so damned afraid of being alone?

Because we’re afraid others will think we’re lonely. There’s something wrong with lonely people, or else why wouldn’t they have people around them? There must be something broken about them! If you learn someone is lonely, you best stay away from them. Leave them to their cats. Loneliness results in more loneliness; it’s a beast that feeds itself. (Please know that I don’t believe any of this — or at least I don’t want to, but these are thoughts that I hear in my head, because Society)

I’m not lonely! I have 2200 facebook friends. Look at all the things I share. Look at all those likes! I have all the likes! And retweets. Don’t even get me started on retweets. I have to call them RTs because I get so many I don’t even have time for all those other letters. Look at me on Instagram! Follow me! #TeamFollowBack Connect with me! Please, please, connect with me. How am I so damned lonely?! Nobody else feels this lonely. Look at all the friends they have on Facebook. Look at all those likes they’re getting…

We are living in a time when it’s easy to feel uncomfortable being alone, because there are so many ways you can “be” with other people. So we’re never truly alone. And that makes it ever more uncomfortable when we feel lonely.

I saw someone post a photo on Facebook last Friday night of themselves with a glass of wine and the caption “Relaxing into a much-needed quiet Friday night date with myself. #DontHate”

The irony hurt. If you really want to be alone, WHY ARE YOU TELLING THE WHOLE WORLD, my brain yelled.

Then I realized I knew the answer: this person is uncomfortable being alone on a Friday night, and this is how they are trying to mitigate that discomfort.

They are seeing all of their friends posting photos of their fun nights out with dozens of people and having so much fun and internalizing all of this as something being wrong with them. Maybe they chose to be alone tonight, or maybe they got ditched by a friend, or maybe they wanted to go out and don’t really have any friends who wanted to go out with them, but, whatever the case, they were probably terrified they would slip from enjoying a night alone into being lonely on a Friday night. The first is good. The second is bad. And maybe a “like” or a reassuring comment would stave that off.

spend a lot of time on the road traveling alone. And during the day, when I’m performing, or visiting a campus, or flying, eating, writing — keeping my mind busy — I’m on the road traveling alone; I’m not lonely on the road. And I enjoy it. I enjoy the aloneness. I thrive in it. But at night, when I get back to my hotel room and plop down on the bed, I regularly toe the line between being alone and being lonely.

I am usually good at landing on the enjoying a night alone side of the line, but sometimes, usually after a particularly long stretch on the road, of if a show doesn’t go as well as I want it to, I’ll find myself stumbling onto the lonely side. It probably doesn’t help that I have this disgusting and self-body-destroying habit of having a huge pizza delivered to my hotel room and eating it by myself in my underwear. And, as I am typing that, I am reminded of this

Joe Biden and NATO

President Joe Biden’s first overseas trip put his political and negotiating philosophy ahead of everyone, as he gathered traditional US democratic allies to tackle new and old challenges and proposed an often-rosy take on the options of cooperation with Russian President Vladimir Putin after a one-on-one summit.

Here are some key takeaways:

Biden and Putin didn’t use the word “reset” to label the condition of affairs between the 2 nations after their summit in Switzerland. But that’s what the meeting amounted to, with both men risking out clear areas of divergence, even as they pointed to smaller-scale areas where they could unite.

They expressed both a joint respect and a mutual scepticism. It was an sudden return to more conservative US-Russia inclosing after the presidency of Donald Trump, who often seemed to raise Putin and create at least the ambition that the countries could be more like partners.

This time, each leader left with the estimation that some of the old rules still apply. Russia returns to its place as a “worthy adversary,” as Biden put it, rather than some quite associate. And the longer-standing tensions, over cyberwarfare and human rights, remain.

After their three-hour meeting, Biden’s sunny character stood in sharp difference to the more sober, taciturn tone of Putin, who at times became self – justifying when asked questions by reporters about human rights violations in Russia and therefore the country’s attacks of Ukraine.

Even so, Biden recognized his optimism was more wishful thinking than reality.

“I’m getting to drive you all crazy because i do know you want me to always put a negative thrust on things, particularly publicly ,” he said shortly before boarding Air Force One, adding, that way, “you guarantee nothing happens.”

It emphasized the president’s talking style, whether it’s with Putin or with Senate Republicans reception on infrastructure — during which he publicly expresses his confidence that a deal can be struck despite often overwhelming odds.

“I know we make policy bent be this great, great skill that somehow quite “> is sort of kind of a cipher ,” Biden said. “All policy could also be a logical extension of personal relationships. It’s the way human nature functions.”

He later added, “There’s a worth to being realistic and to put on an optimistic front, an optimistic face.”

Biden’s eight-day, three-country foreign trip established his emphasis on private relationships above all.

“There’s no substitute, as those of you who have covered me for a quick time know, for face-to-face dialogue between leaders. None,” Biden said, stating his summit with Putin successful simply for the actual fact that they spoke face to face .

Throughout his trip, most of Biden’s meetings were conducted privately , without cameras, or with only a couple of moments hospitable media.

It highlighted Biden’s faith in immaterial personal ties that can drive policy outcomes, both foreign and domestic.

And it marked a clear leaving in style from Trump, whose carefree public meetings with global leaders became something of legend on the international stage. Relationships inclined to flow one way — with sycophantic public displays by heads of state and government trying to get on Trump’s good side.

Biden is banking that those leaders will welcome a return to the “old school” approach.